Circulation Research “In This Issue” Anthology
2019; Lippincott Williams & Wilkins; Volume: 124; Issue: 12 Linguagem: Inglês
10.1161/res.0000000000000275
ISSN1524-4571
Autores Tópico(s)ATP Synthase and ATPases Research
ResumoHomeCirculation ResearchVol. 124, No. 12Circulation Research "In This Issue" Anthology Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBCirculation Research "In This Issue" Anthology Ruth Williams and The Editors Ruth WilliamsRuth Williams and The Editors Originally published6 Jun 2019https://doi.org/10.1161/RES.0000000000000275Circulation Research. 2019;124:e123–e148Circulation Research, vol 122, 2018Altered Mitochondrial Dynamics in Lipotoxic Hearts (p 58)1Excess lipids meddle with mitochondrial function in the heart, report Tsushima et al.Download figureDownload PowerPointObesity and diabetes are 2 major risk factors for heart disease and can lead to myocardial lipotoxicity—cardiac dysfunction caused by excessive fatty acid accumulation. At a pathological level, lipotoxicity has been associated with mitochondrial dysfunction, but exactly how excess lipids affect mitochondria is unclear. To find out, Tsushima and colleagues studied mice that were genetically engineered to accumulate excess fatty acids specifically in their cardiac myocytes. These animals ultimately developed heart failure, but not until they are ≈4 months old, giving the team the opportunity to study pathological progression of lipotoxicity. In early weeks of life, excess lipids were associated with an increase in mitochondrial activity. Prolonged excess, however, caused the mitochondria to produce high levels of reactive oxygen species, which in turn led to post-translational modifications of proteins involved in mitochondrial fusion and fission. Indeed, the team also observed that cardiac mitochondria in these mice were abnormally thin and fragmented. On the basis of these findings, the authors suggest that lipid-induced perturbation of mitochondrial dynamics could be an important pathological mechanism in lipotoxic cardiomypathies.Cell Cycle Activity and Cardiac Cell Therapy (p 88)2Boosting proliferation in stem cell-derived cardiomyocytes could improve their regenerative potential, say Zhu et al.Download figureDownload PowerPointCardiac cells have limited capacity to divide. Most adult cardiac myocytes are postmitotic, and while cardiac progenitors are present and able to divide, they are unable to restore sufficient muscle to fully repair a heart after a myocardial infarction. The efficacy of exogenous cells to repair the damage has been tested in animals and patients, but regardless of the cell type used, regeneration is often limited by poor retention of the cells in the myocardium. Zhu and colleagues hypothesized that if the transplanted cells could be prompted to proliferate, those that do engraft may multiply and provide a better chance of repair. To test this, the team over-expressed the cell cycle promoter CCND2 in human induced pluripotent stem cells (hiPSCs) and then differentiated these cells into cardiac myocytes (CM). The hiPSC-CMs proliferated more in culture than their wild-type counterparts and, when injected into mice with injured hearts, were more effective at reducing infarct size and at restoring heart function. The results suggest that promoting proliferation of therapeutic cells, whether genetically or pharmacologically, might be a way to improve cell-based therapies for heart regeneration.Sex Hormones, Carotid Plaque Composition, and Stroke (p 97)3Glisic et al investigate the effects of sex hormones on stroke risk and atherosclerosis.Women with atherosclerosis tend to exhibit plaques with more stable compositions than men. Women are also less likely to suffer strokes. But 10 years after menopause, a women's risk of stroke almost doubles. These sex- and menopause-associated differences led Glisic and colleagues to investigate the role of sex hormones. Indeed, both estradiol and testosterone are known to affect the vascular system in a variety of ways. The team studied 645 postmenopausal women (average age, 65) and 835 similarly aged men with atherosclerosis. Testosterone and estradiol levels were assessed, along with plaque composition and stroke risk in a 10-year follow up. They found that women with detectable estradiol had both an increased risk of stroke and an increased likelihood of having unstable plaques (intraplaque hemorrhages) than women with undetectable estradiol. This association was not observed in men, and testosterone levels showed no associations. These results are consistent with previous studies suggesting that hormone replacement therapy could have harmful vascular effects in elderly women compared with women closer to menopause age. The study, thus, raises further concerns about the use of hormone-replacement therapy in postmenopausal women, say the authors.Quaking Inhibits Doxorubicin Cardiotoxicity (p 246)4An RNA-binding protein called Quaking protects heart cells from toxic chemotherapy, report Gupta et al.Download figureDownload PowerPointThe cancer drug doxorubicin is cardiotoxic; it causes myocardial apoptosis and atrophy that can ultimately lead to heart failure. Developing less toxic chemotherapeutics would be ideal, but in the interim, there is immediate clinical need to reduce the cardiotoxicity of doxorubicin, without impairing its efficacy. For this, it is important to develop a thorough understanding of the molecular pathology of doxorubicin-induced cardiotoxicity. Gupta and colleagues performed transcriptome analysis on the hearts of mice treated or not treated with doxorubicin. Among the many RNAs differentially expressed, they found significant down-regulation of Quaking (Qki) in treated hearts. This circular RNA-regulating protein has been previously shown to prevent apoptosis during myocardial injury. Indeed, the team found that not only were some circular RNAs misregulated in the doxorubicin-treated hearts, but that over-expression of Qki attenuated doxorubicin-induced cardiac myocyte apoptosis and atrophy in vitro and in mice. These results suggest that boosting levels of Qki in patients receiving doxorubicin chemotherapy may be a potential means of protecting their hearts from the drug's toxic effects.MSC Immunomodulation and Atherosclerosis (p 255)5Mitochondrial oxidative stress reduces MSC immunopotency in atherosclerosis sufferers, report Mancini et al.Download figureDownload PowerPointMesenchymal stem cells (MSCs) are known for their natural immunomodulatory properties and, as such, have been used in clinical trials to treat coronary artery disease caused by atherosclerosis. But results from these trials have been less promising than expected: in part because autologous MSCs from atherosclerosis patients have impaired anti-inflammatory capacities. Mancini and colleagues investigated the molecular underpinnings of this reduced potency, and they found evidence showing that mitochondrial oxidative stress is increased in patient cells. They analyzed MSCs from 80 individuals with and without atherosclerosis and discovered that cells from patients with atherosclerosis had increased levels of reactive oxygen species (ROS), and were less effective at suppressing T-cell proliferation in vitro than those from healthy individuals. Furthermore, pharmacological reduction of ROS levels in the MSCs from atherosclerosis patients lowered inflammatory cytokine production and improved the T-cell–suppressing effects. Together, the results indicate that lowering mitochondrial oxidative stress in autologous MSCs may improve the efficacy of these cells for treating coronary artery disease.iPSC-EVs for Myocardial Repair (p 296)6Extracellular vesicles offer safe and effective alternative to iPSC therapy for myocardial infarction, say Adamiak et al.Download figureDownload PowerPointThe therapeutic use of stem and progenitor cells for treating injured myocardium has been extensively investigated in both animals and patients, but the results so far have shown only modest efficacy. It is currently believed that these cells act as a source of secreted factors to promote regeneration and that such paracrine effects could be delivered either directly or via extracellular vesicles (EVs)—small membrane-bound packages of cellular contents. Adamiak and colleagues, therefore, investigated whether EVs exert beneficial factors and if so, whether these vesicles alone could provide effective treatment. They examined the contents of EVs from mouse induced pluripotent stem cells (iPSCs) and found that they contain an abundance of proangiogenic and cytoprotective factors. In agreement with these findings, they found that when the EVs were transplanted into the hearts of mice after myocardial infarction, the vesicles promoted healing and heart function more effectively that iPSCs themselves. Importantly, although many of the mice injected with iPSCs developed cardiac tumors, no tumors were observed in the EV-treated animals. The authors conclude that EVs may be a safer and more effective option than iPSCs for treating infarcted hearts.Open Software to Quantify Cardiac Contraction (p e5)7Sala et al create MUSCLEMOTION, an open-source software for quantifying contractions in both heart muscle cells and tissues.Download figureDownload PowerPointMeasurement and analysis of cardiac contractility are of high importance in studying muscle function, assessing disease phenotypes, and evaluating drug toxicity. Unlike electrophysiological measurements, for which there are well-established and standardized techniques applicable to a range of samples, the techniques for measuring myocardial contractions tend to be sample-specific, not easily comparable, and require specialized expertise. Sala and colleagues have now developed a novel software that can quantify contractions in movies of specimens as diverse as single heart cells, cultured cardiac myocytes, 3D cardiac organoids, and even living Zebrafish hearts. They tested the ability of their software, called MUSCLEMOTION, to detect drug-induced and disease-related contraction differences in a variety of samples and showed that the performance of the software was comparable to various gold-standard techniques tailored to those specific samples. By making MUSCLEMOTION user-friendly and freely accessible, the authors hope to facilitate comparisons of contraction data, not just between samples, but between laboratories as well, thereby facilitating data replication and reproducibility.64 Novel Genetic Loci for Coronary Artery Disease (p 433)8Van der Harst and Verweij provide evidence for an omnigenic model of coronary artery disease.Download figureDownload PowerPointCoronary artery disease (CAD) is a multifactorial condition with contributions from both genetic and environmental factors. It has been associated with a number of genetic loci, yet linking these to potential pathological pathways remains difficult. Van der Harst and Verweij have now carried out the largest GWAS (genome-wide association study) to date. Examining nearly 8 million single nucleotide polymorphisms (SNPs) in a total of 122 733 CAD patient samples, they identified 64 novel CAD-associated loci. These candidate genes, however, are involved in such broad biological functions and expressed in such diverse tissues that the contribution of genetic factors appears to be even more complicated than first thought, as many loci have no obvious link to CAD. Based on these findings, the authors suggest that the model of CAD as a polygenic disease—one caused by multiple genes affecting a handful of key pathways—may be incorrect. Instead, they surmise that the results point to an omnigenic model—whereby the link between many SNPs and CAD may be one of interconnectedness of gene-regulatory mechanisms. If so, determining cell-specific networks of gene expression may be the best route to understanding CAD pathology.Long-Term MRI Follow-Up of MVO After Cell Therapy (p 479)9Traverse et al report the final 2-year results of the stem cell TIME trial.Download figureDownload PowerPointStem cell therapies are under investigation for their potential to promote cardiac tissue repair after myocardial infarction (MI). Because changes to the myocardium following reperfusion could influence cell engraftment and survival, the timing of cell delivery was examined in the TIME trial (Timing In Myocardial Infarction Evaluation), which compared delivery of cells on day 3 with day 7 following MI in 120 patients. At 6 months, the results indicated that cells delivered at either time point offered no benefits to patients. And 2 years later, these results remain the same. However, the study has also provided one of the largest MRI datasets of patients following MI. By analyzing these data, Traverse and colleagues show that patients who had microvascular obstructions at baseline have poorer outcomes—larger infarct size, more adverse left ventricle remodeling, reduced recovery of ventricle function, and greater likelihood of requiring an implantation device. From these findings, the team suggests that the presence of microvascular obstruction may be a powerful predictor of subsequent left ventricle failure, and that microvascular dysfunction identifies the most at-risk patients.Novel Mouse Model of Atherosclerosis Regression (p 560)10Basu et al develop a method for studying atherosclerosis regression in mice.Download figureDownload PowerPointMice genetically engineered to be deficient in either apolipoprotein E (ApoE) or the LDL receptor (LDLR) are models of choice for studying atherosclerosis. Such models have enabled researchers to gain a detailed understanding of how diet, genetic background, and other factors affect the development of atherosclerotic lesions. However, there are few animal models that mimic regression of the disease, and those that do require either complicated surgeries or time-consuming breeding. To address this, Basu and colleagues have developed an alternative model. First, the researchers induce atherosclerotic plaques in wild-type mice using a combination of high-fat diet and repeated injections (1 per week for 16 weeks) of an LDLR-suppressing antisense oligonucleotide. Then, they give the animals injections of an LDLR sense oligonucleotide to restore receptor expression. This both reduces plasma cholesterol and diminishes the immune cell content of the plaques. With the benefit of using normal laboratory mice, this simple yet effective approach should expedite research into both development and regression of atherosclerosis, say the authors.Bone Marrow Lineages and Infarct Fibroblasts (p 583)11Moore-Morris et al investigate the origins of scar fibroblasts after myocardial infarction.Download figureDownload PowerPointLarge numbers of cardiac myocytes can be destroyed by a myocardial infarction, and because these cells are not readily replenished, functional muscle is replaced with a collagen-rich, fibrous scar created by fibroblasts. But it is unclear where these fibroblasts come from. Some reports suggest they are derived from endothelial-to-mesenchymal transition, while other investigators suggest that circulating fibroblast progenitors from bone marrow are the source. Yet others suspect that the fibroblasts arise from the epicardium of the heart itself. To find out, Moore-Morris and colleagues performed a series of lineage-tracing experiments in mice subjected to myocardial infarctions. Their results showed that fibroblasts within the infarcted myocardium were not derived from endothelial-to-mesenchymal transition, and were not of either bone marrow or hematopoietic origin (with the exception of a small number of fibroblasts on the surface of the injured heart). Indeed, within the scar tissue itself, the authors discovered that 96% of the fibroblasts were of epicardial origin. Identifying the fibroblast source could provide insights into how to modulate the fibrotic process to reduce scarring and maximize heart function.Spironolactone Inhibits Panx1 (p 606)12Good et al identify spironolactone as a potent inhibitor of pannexin 1.Download figureDownload PowerPointHypertension is a major risk factor for cardiovascular disease, and it affects ≈40% of adults worldwide. In many cases, first-line therapies do not adequately control hypertension. Identifying alternative clinical targets is, therefore, a major research goal. One potential druggable target is pannexin 1—a nucleotide release channel implicated in many physiological and pathophysiological processes, including vasoconstriction via α-adrenergic-induced ATP release. Good and colleagues performed an unbiased screen of small molecule pannexin 1 inhibitors and, in so doing, identified the known antihypertensive drug spironolactone. Interestingly, spironolactone, which is a diuretic, was believed to have antihypertensive effects not explained by its known mechanism of action. Thus, its inhibition of pannexin 1 may be such an off-target effect. The team went on to confirm that spironolactone could inhibit α-adrenergic-induced vasoconstriction in arterioles from hypertensive mice and humans, and could reduce blood pressure in mice. Both effects depended upon smooth muscle expression of pannexin 1. Together, these results bolster the idea that pannexin 1 inhibition could be an effective pharmacological strategy for the management of treatment-resistant hypertension.Clonal Expansion of Endothelial Cells (p 670)13How blood vessels grow depends on the physiological context, say Manavski et al.Download figureDownload PowerPointThe requirement for new blood vessels is minimal, once human development is complete. However, after tissue ischemia, such as a myocardial infarction, new capillaries grow to restore oxygen to the hypoxic tissue. Manavski and colleagues now show that in confetti mice—animals engineered to have different colored cells for the purposes of lineage tracing—the process of neovascularization differs depending on whether it is a normal part of development or induced via hypoxia. The team found that during normal postnatal retinal angiogenesis in the mice, new blood vessels were formed from the random integration, or mixing, of endothelial cells—evinced by an assortment of different colored cells comprising the vessels. When the animals' retinas were temporarily exposed to hypoxia, however, neovascularization resulted largely from the clonal expansion of endothelial cells (cells of one color dominated). Endothelial cell clonal expansion also drove neovascularization after myocardial infarction and hind limb ischemia in the mice. Knowing how endothelial cells behave during hypoxia could help guide strategies for treating ischemic diseases, as well as prevention of pathological vascularization.Improved Survival Upon Suppression of FOXO TFs in Laminopathies (p 678)14FOXO transcription factors contribute to cardiac problems in laminopathies, report Auguste et al.Download figureDownload PowerPointClassical laminopathies, such as Emery-Dreifuss muscular dystrophy and Hutchinson-Gilford progeria syndrome, are a diverse collection of disorders caused by mutations to LMNA—a nuclear lamina protein. The wide range of phenotypes associated with laminopathies is thought to reflect both the ubiquitous expression of LMNA and its interactions with chromatin across the genome, which could disturb gene expression in a variety of ways. Despite the diverse manifestations of LMNA mutations, most patients die of dilated cardiomyopathy (DCM), a progressive cardiac dysfunction that leads to heart failure. To examine the molecular mechanisms linking LMNA mutation to DCM, Auguste and colleagues studied gene expression in the hearts of LMNA-deficient mice before the animals showed symptoms of cardiac problems. Of the large number of genes aberrantly expressed, transcription factors of the FOXO family were among the most dysregulated. Moreover, knockdown of FOXO 1 and 3 in the hearts of LMNA-lacking mice almost doubled the animals' survival rate. These results indicate that FOXO transcription factors might be key players in DCM and thus potential therapeutic targets for patients with laminopathy-associated heart failure.TRAF-1 Dissects Inflammation and Metabolism (p 693)15Chronic inflammation may protect against metabolic pathology in obesity, say Michel et al.Download figureDownload PowerPointDiet-induced obesity is often associated with chronic inflammation and dysregulated metabolic states—such as hyperlipidemia and insulin resistance. This association suggests that metabolic pathologies, that accompany diabetes, may be in part due to chronic low-grade inflammation. However, obesity-related inflammation may not be solely pathogenic, as inhibition of some inflammatory pathways in mice has been found to aggravate obesity or metabolic dysregulation. To examine the role of inflammation in obesity in greater detail, Michel et al studied mice engineered to lack the anti-inflammatory factor TRAF-1 (tumor-necrosis receptor–associated factor 1), which the authors found was upregulated in obese mice and humans. While the TRAF-1 null mice exhibited increased inflammatory cytokine release from adipose tissue with increased immune cell recruitment, the animals did not gain weight on par with wild-type mice when fed a high-fat diet. In comparison with wild-type mice, TRAF-1 null mice also showed improved insulin resistance and greater lipid breakdown. Furthermore, this increased lipolysis was shown to require inflammatory signaling. Together, these results add to the growing body of evidence that in the setting of obesity inflammation is not purely pathogenic, and requires further investigation.JNK2/CaMKII Crosstalk Underlies Atrial Arrhythmias (p 821)16Inhibiting JNK2 reduces the risk of atrial fibrillation, report Yan et al.Download figureDownload PowerPointCharacterized by a rapid and irregular heartbeat, atrial fibrillation (A-Fib) is associated with hypertrophy, heart failure, ischemia, and old age. Indeed, between 10 and 15% of 70- to 80-year olds develop A-Fib. However, in addition to A-Fib, the activity of the stress–response enzyme c-Jun N-terminal kinase (JNK) also increases with age, hypertrophy, heart failure, and ischemia, which prompted Yan and colleagues to investigate whether A-Fib and JNK share a more direct link. Focusing on JNK2, which is the major JNK isoform in the heart, the team confirmed that the activity of the enzyme is positively correlated with age in both human and mouse hearts. They then showed that elevating JNK2 activity in young mice caused abnormal intracellular calcium handling in the heart, and that JNK2 phosphorylated and activated the protein kinase CamKII, a known driver of arrhythmia. Moreover, inhibition of JNK2 in older animals prevented CamKII activation, aberrant calcium handling, and, most importantly, A-Fib susceptibility. As JNK2 inhibitors are currently under clinical investigation for the treatment of cancer and arthritis, these inhibitors may be attractive candidates for preventing or treating A-Fib.CYB561 and Orthostatic Hypotension (p 846)17van den Berg et al discover a new mutation underlying orthostatic hypotension.Download figureDownload PowerPointOrthostatic hypotension—a sudden drop in blood pressure upon standing after lying or sitting—can cause dizziness, fainting, and even loss of consciousness. Although mild or occasional cases are common, in some people, the condition can be severe enough to be life-threatening. Some individuals with mutations in the enzyme dopamine β-hydroxylase (DβH), for example, have impaired production of the catecholamines, norepinephrine and epinephrine, and, as a result, dangerously low blood pressure. Now, van den Berg and colleagues have uncovered a new genetic cause of orthostatic hypotension. They found that 4 patients (2 sets of sisters) with severe, life-long illness and with catecholamine levels indicative of DβH deficiency, did not in fact have DβH mutations or reduced DβH activity. Instead, genetic analysis, including whole-exome sequencing, revealed that the women had homozygous mutations in the gene encoding cytochrome b561 (CYB561)—a transmembrane electron transporter. Investigations into the functional consequences showed that these mutations perturbed electron shuttling necessary for norephinephrine synthesis. Encouragingly, treatment with the norephinerine precursor L-dihydroxyphenylserine, while producing unpleasant side effects, increased blood pressure and relieved symptoms in all 4 patients.Vascular RvDn-3 DPA Reduce Systemic Inflammation (p 855)18RvDn-3 DPA tempers the daily increase in leukocyte and platelet activation, report Colas et al.Download figureDownload PowerPointSpecialized proresolving mediators (SPMs) are recently identified molecules that promote the resolution of inflammation. Armed with the knowledge that inflammation naturally waxes and wanes at different periods of night and day, Colas and colleagues investigated whether SPM levels might also exhibit diurnal variation. They found that blood obtained from healthy volunteers at regular intervals over a 24-hour period had higher level of the SPM RvDn-3 DPA at night and that these levels dropped in the morning, coincident with increased leukocyte activation. Moreover, incubation of whole blood with RvDn-3 DPA caused a decrease in neutrophil, platelet, and monocyte activation. Because such leukocyte and platelet activation are linked with cardiovascular disease (CVD)—and to increased occurrence of adverse cardiovascular events in the morning—the team measured RvDn-3 DPA in patients with CVD. They found that, compared with healthy controls, people with CVD had lower levels of RvDn-3 DPA and that the diurnal regulation of the SPM RvDn-3 DPA was impaired. Taken together, these findings suggest that RvDn-3 DPA moderates the diurnal elevations in leukocyte activation and that loss of this regulation may lead to CVD.Lack of Cardiac Remuscularization by ESCs in Primates (p 958)19Human stem cell–derived cardiovascular progenitors do not remuscularize the infarcted hearts of nonhuman primates, say Zhu et al.Download figureDownload PowerPointHuman pluripotent stem cells (hPSCs) are under investigation for their potential to serve as regenerative treatments after myocardial infarction (MI). Indeed, several studies indicate that hPSC-derived cardiovascular progenitors (hPSC-CVPCs) improve recovery from MI in model organisms. Nevertheless, the mechanisms by which human cells promote myocardial recovery after infarction remain unclear. Such mechanisms can be tested by transplanting human cells in nonhuman primates, but such xenotransplant studies are limited by immune rejection of the cells, which prevents their long-term engraftment. Now, Zhu and colleagues have tested the effectiveness of 2 immunosuppression regimens—cyclosporine alone and cyclosporine plus methylprednisolone and basiliximab—for their ability to improve hPSC-CVPC engraftment in 32 cynomolgus monkeys after MI. Compared with the single-drug treatment, the team found that the combination regimen increased cell retention, reduced apoptosis, and improved heart function after 1 month. By 140 days, however, no cells remained in the hearts of animals in either treatment group. Direct remuscularization by the cells can, therefore, be excluded as the mechanism of functional improvement, say the authors.C3aR/C5aR in Tregs Regulates Hypertension (p 970)20Lack of the complement receptors C3aR and C5aR protect mice against hypertension, report Chen et al.Download figureDownload PowerPointHypertension is a leading risk factor for coronary artery disease, stroke, and heart failure. To study the condition in mice, researchers experimentally induce hypertension with either angiotensin II or a combination of deoxycorticosterone acetate and salt. Such induced hypertension has been shown to depend on the presence of T-effector cells. Immunosuppressive T-regulatory cells (Tregs), by contrast, are protective against high-blood pressure. Secreted immune proteins of the complement system—C3a and C5a—have been shown to downregulate Tregs, leading Chen and colleagues to predict that absence of the C3a and C5a receptors would protect against hypertension. They found that treatment with Ang II failed to induce hypertension in mice with a double knockout of the C3a and C5a receptors. Furthermore, adoptive transfer of Tregs lacking the receptors to wild-type mice provided greater protection against Ang II–induced hypertension than that conferred by wild-type Tregs. Importantly, the authors found that humans with hypertension have increased expression of the C5a receptor on their Tregs, suggesting the findings of the study may be of relevance to future drug development.Outcomes After Cell Therapy in Single Ventricles (p 994)21Sano et al report improved outcomes for patients with single ventricle heart defects after cardiac stem cell treatment.Download figureDownload PowerPointChildren born with single ventricle hearts have a high risk of heart failure and premature death. The treatment for such congenital heart defects is either a heart transplant or a series of 3 reconstructive surgeries, called staged palliation, during infancy and childhood. In adults with heart failure, stem cell therapies to enhance myocardial function have shown some promise, but whether such therapy could enhance recovery and heart function in single-ventricle patients after surgery is largely unknown. Sano and colleagues compared 41 patients enrolled in either the TICAP or PERSEUS trials—in which patients received intracoronary infusions of autologous cardiosphere-derived cells (CDCs) shortly after stage 2 or 3 surgeries—with 60 patients who underwent staged palliation only. The authors found that at 2 years of follow up, patients who received CDCs had improved ventricular function as well as fewer late failures and adverse events compared with controls
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