Over the last years, stem cell therapy has emerged asan inspiring alternative to restore cardiac function after myocardial infarction. A large body of evidence has been obtained in this field but there is no conclusiv...Over the last years, stem cell therapy has emerged asan inspiring alternative to restore cardiac function after myocardial infarction. A large body of evidence has been obtained in this field but there is no conclusive data on the efficacy of these treatments. Preclinical studies and early reports in humans have been encouraging and have fostered a rapid clinical translation, but positive results have not been uniformly observed and when present, they have been modest. Several types of stem cells, manufacturing methods and delivery routes have been tested in different clinical settings but direct comparison between them is challenging and hinders further research. Despite enormous achievements, major barriers have been found and many fundamental issues remain to be resolved. A better knowledge of the molecular mechanisms implicated in cardiac development and myocardial regeneration is critically needed to overcome some of these hurdles. Genetic and pharmacological priming together with the discovery of new sources of cells have led to a "second generation" of cell products that holds an encouraging promise in cardiovascular regenerative medicine. In this report, we review recent advances in this field focusing on the new types of stem cells that are currently being tested in human beings and on the novel strategies employed to boost cell performance in order to improve cardiac function and outcomes after myocardial infarction.展开更多
Considering the complex nature of the adult heart, it is no wonder that innate regenerative processes, while maintaining adequate cardiac function, fall short in myocardial jeopardy. In spite of these enchaininglimita...Considering the complex nature of the adult heart, it is no wonder that innate regenerative processes, while maintaining adequate cardiac function, fall short in myocardial jeopardy. In spite of these enchaininglimitations, cardiac rejuvenation occurs as well as restricted regeneration. In this review, the background as well as potential mechanisms of endogenous myocardial regeneration are summarized. We present and analyze the available evidence in three subsequent steps. First, we examine the experimental research data that provide insights into the mechanisms and origins of the replicating cardiac myocytes, including cell populations referred to as cardiac progenitor cells(i.e., c-kit+ cells). Second, we describe the role of clinical settings such as acute or chronic myocardial ischemia, as initiators of pathways of endogenous myocardial regeneration. Third, the hitherto conducted clinical studies that examined different approaches of initiating endogenous myocardial regeneration in failing human hearts are analyzed. In conclusion, we present the evidence in support of the notion that regaining cardiac function beyond cellular replacement of dysfunctional myocardium via initiation of innate regenerative pathways could create a new perspective and a paradigm change in heart failure therapeutics. Reinitiating cardiac morphogenesis by reintroducing developmental pathways in the adult failing heart might provide a feasible way of tissue regeneration. Based on our hypothesis "embryonic recall", we present first supporting evidence on regenerative impulses in the myocardium, as induced by developmental processes.展开更多
Background ST segment elevation myocardial infarction （STEMI） remains a major cause of death world-wide. The thrombolysis in myocardial infarction （TIMI） risk score is a risk assessment tool to detect high risk ST...Background ST segment elevation myocardial infarction （STEMI） remains a major cause of death world-wide. The thrombolysis in myocardial infarction （TIMI） risk score is a risk assessment tool to detect high risk STEMI patients. NT-proBNP has been used to assess the severity of heart failure. However, the predictive power of TIMI risk score is not high enough to identify all high-risk patients, and whether NT-proBNP adds power to the TIMI risk score for predicting in-hospital mortality is unclear. Methods 664 STEMI patients were included and divided into 3 groups according to TIMI risk score ≤3 （n=211）, 4-6 （n=281）, and ≥7 （n=172）. The relation-ships between TIM! risk score and events were evaluated. The modified TIMI risk score was constructed through multivariate logistic regression analysis. Results The proportion of in-hospital death （0.5% vs. 3.2% vs. 10.5%, P〈0.001） and major adverse clinical events （MACEs） （14.2% vs. 22.8% vs. 40.1%, P〈0.001） increased as higher TIMI risk score was. ROC curve showed that the AUC of NT-proBNP for predicting in-hospital death was 0.792, with optimal cut-off being 3500pg/mL. Multivariate logistic regression analysis revealed that TIMI risk score （OR=1.26, 95% CI 1.05-1.50, P=0.012） and NT-proBNP〉3500pg/mL （OR=7.30, 95% CI 2.56-20.83, P〈0.001） were independently associated with in-hospital death. Adding NT-proBNP to TIMI risk score produced higher predictive value （AUC： 0.871 vs. 0.804, P=0.040）. Conclusion NT-proBNP is associated with in-hospital death in STEMI patients and has an additive prognostic value to TIMI risk score.展开更多
文摘Over the last years, stem cell therapy has emerged asan inspiring alternative to restore cardiac function after myocardial infarction. A large body of evidence has been obtained in this field but there is no conclusive data on the efficacy of these treatments. Preclinical studies and early reports in humans have been encouraging and have fostered a rapid clinical translation, but positive results have not been uniformly observed and when present, they have been modest. Several types of stem cells, manufacturing methods and delivery routes have been tested in different clinical settings but direct comparison between them is challenging and hinders further research. Despite enormous achievements, major barriers have been found and many fundamental issues remain to be resolved. A better knowledge of the molecular mechanisms implicated in cardiac development and myocardial regeneration is critically needed to overcome some of these hurdles. Genetic and pharmacological priming together with the discovery of new sources of cells have led to a "second generation" of cell products that holds an encouraging promise in cardiovascular regenerative medicine. In this report, we review recent advances in this field focusing on the new types of stem cells that are currently being tested in human beings and on the novel strategies employed to boost cell performance in order to improve cardiac function and outcomes after myocardial infarction.
文摘Considering the complex nature of the adult heart, it is no wonder that innate regenerative processes, while maintaining adequate cardiac function, fall short in myocardial jeopardy. In spite of these enchaininglimitations, cardiac rejuvenation occurs as well as restricted regeneration. In this review, the background as well as potential mechanisms of endogenous myocardial regeneration are summarized. We present and analyze the available evidence in three subsequent steps. First, we examine the experimental research data that provide insights into the mechanisms and origins of the replicating cardiac myocytes, including cell populations referred to as cardiac progenitor cells(i.e., c-kit+ cells). Second, we describe the role of clinical settings such as acute or chronic myocardial ischemia, as initiators of pathways of endogenous myocardial regeneration. Third, the hitherto conducted clinical studies that examined different approaches of initiating endogenous myocardial regeneration in failing human hearts are analyzed. In conclusion, we present the evidence in support of the notion that regaining cardiac function beyond cellular replacement of dysfunctional myocardium via initiation of innate regenerative pathways could create a new perspective and a paradigm change in heart failure therapeutics. Reinitiating cardiac morphogenesis by reintroducing developmental pathways in the adult failing heart might provide a feasible way of tissue regeneration. Based on our hypothesis "embryonic recall", we present first supporting evidence on regenerative impulses in the myocardium, as induced by developmental processes.
文摘Background ST segment elevation myocardial infarction （STEMI） remains a major cause of death world-wide. The thrombolysis in myocardial infarction （TIMI） risk score is a risk assessment tool to detect high risk STEMI patients. NT-proBNP has been used to assess the severity of heart failure. However, the predictive power of TIMI risk score is not high enough to identify all high-risk patients, and whether NT-proBNP adds power to the TIMI risk score for predicting in-hospital mortality is unclear. Methods 664 STEMI patients were included and divided into 3 groups according to TIMI risk score ≤3 （n=211）, 4-6 （n=281）, and ≥7 （n=172）. The relation-ships between TIM! risk score and events were evaluated. The modified TIMI risk score was constructed through multivariate logistic regression analysis. Results The proportion of in-hospital death （0.5% vs. 3.2% vs. 10.5%, P〈0.001） and major adverse clinical events （MACEs） （14.2% vs. 22.8% vs. 40.1%, P〈0.001） increased as higher TIMI risk score was. ROC curve showed that the AUC of NT-proBNP for predicting in-hospital death was 0.792, with optimal cut-off being 3500pg/mL. Multivariate logistic regression analysis revealed that TIMI risk score （OR=1.26, 95% CI 1.05-1.50, P=0.012） and NT-proBNP〉3500pg/mL （OR=7.30, 95% CI 2.56-20.83, P〈0.001） were independently associated with in-hospital death. Adding NT-proBNP to TIMI risk score produced higher predictive value （AUC： 0.871 vs. 0.804, P=0.040）. Conclusion NT-proBNP is associated with in-hospital death in STEMI patients and has an additive prognostic value to TIMI risk score.
