Stem cell therapy for chronic heart failure: an updated appraisal.

INTRODUCTION: Significant advances have been made to understand the mechanisms involved in cardiac cell-based therapies. The early translational application of basic science knowledge has led to several animal and human clinical trials. The initial promising beneficial effect of stem cells on cardiac function restoration has been eclipsed by the inability of animal studies to translate into sustained clinical improvements in human clinical trials. AREAS COVERED: In this review, the authors cover an updated overview of various stem cell populations used in chronic heart failure. A critical review of clinical trials conducted in advanced heart failure patients is proposed, and finally promising avenues for developments in the field of cardiac cell-based therapies are presented. EXPERT OPINION: Several questions remain unanswered, and this limits our ability to understand basic mechanisms involved in stem cell therapeutics. Human studies have revealed critical unresolved issues. Further elucidation of the proper timing, mode delivery and prosurvival factors is imperative, if the field is to advance. The limited benefits seen to date are simply not enough if the potential for substantial recovery of nonfunctioning myocardium is to be realized.

Effects of the number and interval of balloon inflations during primary PCI on the extent of myocardial injury in patients with STEMI: does postconditioning exist in real-world practice?

UNLABELLED: Postconditioning reduces infarct size in animal models and clinical studies. The present retrospective study aimed to evaluate the effects of the number and interval delay of balloon inflations during primary percutaneous coronary intervention (PCI) on enzymatic infarct size, myocardial perfusion and cardiac function in patients with ST-segment elevation myocardial infarction (STEMI) in routine clinical practice. METHODS: Of the 433 STEMI patients who underwent primary PCI at Vanderbilt University Medical Center from October 2003 to August 2007, 85 (19.6%) met criteria and were enrolled into two groups: those with > or = 3 versus with < or = 2 balloon inflations. Peak CK, ST-segment resolution, myocardial blush grade (MBG) and left ventricular (LV) function were compared between the two groups. Correlations of peak CK, MBG and LV ejection fraction (LVEF) with the number, average duration and the first delay interval of balloon inflations were analyzed. A stepwise multiple regression analysis was used to identify the possible determinants of echocardiographic LVEF. RESULTS: The LV end-systolic volume (LVESV) index in the group with > or = 3 inflations was significantly lower than that with < or = 2 inflations (33.1 +/- 7.9 ml/m square vs. 37.5 +/- 11.2 ml/m square p = 0.036), while LVEF was significantly higher (50.4 +/- 6.3% versus 46.1 +/- 8.5%; p = 0.009). Post hoc analysis showed peak CK in patients with 4 inflations was significantly lower than that with < or = 2 inflations (1,698 +/- 1,266 IU/L vs. 2,603 +/- 1,532 IU/L; p < 0.05). There was a positive correlation between LVEF and the number of balloon inflations (r = 0.222, p = 0.041). CONCLUSIONS: Repetitive balloon inflations during primary PCI appear to confer cardioprotection. The data suggest that postconditioning may exist in real-world practice and contribute to myocardial protection.

Stem cell therapy for cardiac repair: benefits and barriers.

Cardiovascular disease remains the leading cause of death worldwide. Acute ischaemic injury and chronic cardiomyopathies lead to permanent loss of cardiac tissue and ultimately heart failure. Current therapies aim largely to attenuate the pathological remodelling that occurs after injury and to reduce risk factors for cardiovascular disease. Studies in animal models indicate that transplantation of mesenchymal stem cells, bone-marrow-derived haematopoietic stem cells, skeletal myoblasts, or embryonic stem cells has the potential to improve the function of ventricular muscle after ischaemic injury. Clinical trials using primarily bone-marrow-derived cells and skeletal myoblasts have also produced some encouraging results. However, the current experimental evidence suggests that the benefits of cell therapy are modest, the generation of new cardiac tissue is low, and the predominant mechanisms of action of transplanted stem cells involve favourable paracrine effects on injured myocardium. Recent studies show that the adult heart possesses various pools of putative resident stem cells, raising the hope that these cells can be isolated for therapy or manipulated in vivo to improve the healing of cardiac muscle after injury. This article reviews the properties and potential of the various stem cell populations for cardiac repair and regeneration as well as the barriers that might lie ahead.