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.

C ongenital coronary artery anomalies (CCAs) are important causes of sudden cardiac arrest (SCA).1-3 We report the case of a patient in whom the mode and pathophysiology of SCA were documented to a thorough degree. The details of this case add to our knowledge of CCAs and the mechanisms of SCA in young athletes who have these rare conditions. Case ReportA 26-year-old woman, a well-trained and accomplished runner (body mass index, 16.7 kg/m 2 ), collapsed 200 meters from the finish line of a 26.2-mile marathon after running for 3 hours 27 minutes. She was rushed to a nearby medical tent and was found to be pulseless. A rhythm strip revealed ventricular fibrillation. After undergoing brief chest compressions, she was given 1 mg of intravenous epinephrine followed by 2 direct-current cardioversions. Sinus rhythm was restored, and a pulse was palpable.The patient was intubated and transported to a nearby hospital, where a 12-lead electrocardiogram showed sinus tachycardia with inferolateral ST-segment depression. She was rushed to our tertiary center. A peak troponin I level of 1.88 ng/mL and a creatine kinase level of 6,426 U/L were noted. Thirty-six hours after the SCA and after hypothermia was discontinued, she made a full neurologic recovery. She was soon weaned from mechanical ventilation.On day 6 after the SCA, echocardiograms showed normal left ventricular (LV) wall thickness and motion. Cardiac magnetic resonance images revealed that the left main coronary artery (LMCA) originated ectopically from the right coronary sinus (Fig. 1) and that the proximal left main (LM) trunk probably had an intramural course, inside the aortic wall. The LMCA ran between the aorta and pulmonary artery (pursuing an interarterial or "preaortic" course) before branching into the left anterior descending coronary artery (LAD) and left circumflex coronary artery. A viability study showed only small focal areas of intramural hyperenhancement, suggesting a small scar, at the mid-anteroseptal LV wall. On day 9, coronary angiograms revealed an anoma-

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.