The limited ability of mammalian adult cardiomyocytes to proliferate following an injury to the heart, such as myocardial infarction, is a major factor that results in adverse fibrotic and myocardial remodeling that ultimately leads to heart failure. The continued high degree of heart failure-associated morbidity and lethality requires the special attention of researchers worldwide to develop efficient therapeutics for cardiac repair. Recently, various strategies and approaches have been developed and tested to extrinsically induce regeneration and restoration of the myocardium after cardiac injury have yielded encouraging results. Nevertheless, these interventions still lack adequate success to be used for clinical interventions. This review highlights and discusses both cell-based and cell-free therapeutic approaches as well as current advancements, major limitations, and future perspectives towards developing an efficient therapeutic method for cardiac repair.

Two prevalent harvesting techniques are routinely utilized in coronary artery bypass grafting (CABG): endoscopic vein harvesting (EVH) and open vein harvesting (OVH). Our purpose is to compare mid-term and long-term outcomes between these two techniques for CABG. After the acquisition of evidence, available studies assessing both harvesting techniques with follow-up precondition (a minimum of one year) were identified. The primary outcome was all-cause mortality. Secondary outcomes of interest included the number of intra-operative graft injuries, leg-wound complications, in-hospital mortality, major adverse cardiac events (MACE) and graft patency. Twenty-two studies including 27911 patients were identified. The incidences of all-cause mortality, in-hospital death, and MACE were similar between EVH and OVH. EVH was associated with more graft injuries (weighted mean difference (WMD) 0.73; 95% confidence interval (CI) 0.18-1.28; P = 0.009), lower mid-term graft patency (odds ratio (OR) 0.80; 95% CI 0.70-0.91; P = 0.0005), and decreased long-term graft patency (OR 0.15, 95% CI 0.04-0.61; P = 0.008) as compared with OVH. Fewer leg-wound complications were observed in endoscopic harvesting as compared to conventional technique (OR 0.19, 95% CI 0.12-0.30; P < 0.001). Data from subgroup analysis suggested study period as a key factor affecting the outcomes for graft patency. The risks for all-cause mortality, in-hospital death, and MACE are similar between EVH and OVH. EVH increases conduit injuries and lowers mid-long term graft patency rates, however, study period, with growing surgical expertise, may be associated with better outcomes.

BACKGROUND: Cardiac transverse tubules (T-tubules) are anchored to sarcomeric Z-discs by costameres to establish a regular spaced pattern. One of the major components of costameres is the dystrophin-glycoprotein complex (DGC). Nevertheless, how the assembly of the DGC coordinates with the formation and maintenance of T-tubules under physiological and pathological conditions remains unclear. METHODS: Given the known role of Ptpn23 (protein tyrosine phosphatase, nonreceptor type 23) in regulating membrane deformation, its expression in patients with dilated cardiomyopathy was determined. Taking advantage of Cre/Loxp, CRISPR/Cas9, and adeno-associated virus 9 (AAV9)–mediated in vivo gene editing, we generated cardiomyocyte-specific Ptpn23 and Actn2 (α-actinin-2, a major component of Z-discs) knockout mice. We also perturbed the DGC by using dystrophin global knockout mice ( Dmd ^E4* ). MM 4-64 and Di-8-ANEPPS staining, Cav3 immunofluorescence, and transmission electron microscopy were performed to determine T-tubule structure in isolated cells and intact hearts. In addition, the assembly of the DGC with Ptpn23 and dystrophin loss of function was determined by glycerol-gradient fractionation and SDS-PAGE analysis. RESULTS: The expression level of Ptpn23 was reduced in failing hearts from dilated cardiomyopathy patients and mice. Genetic deletion of Ptpn23 resulted in disorganized T-tubules with enlarged diameters and progressive dilated cardiomyopathy without affecting sarcomere organization. AAV9-mediated mosaic somatic mutagenesis further indicated a cell-autonomous role of Ptpn23 in regulating T-tubule formation. Genetic and biochemical analyses showed that Ptpn23 was essential for the integrity of costameres, which anchor the T-tubule membrane to Z-discs, through interactions with α-actinin and dystrophin. Deletion of α-actinin altered the subcellular localization of Ptpn23 and DGCs. In addition, genetic inactivation of dystrophin caused similar T-tubule defects to Ptpn23 loss-of-function without affecting Ptpn23 localization at Z-discs. Last, inducible Ptpn23 knockout at 1 month of age showed Ptpn23 is also required for the maintenance of T-tubules in adult cardiomyocytes. CONCLUSIONS: Ptpn23 is essential for cardiac T-tubule formation and maintenance along Z-discs. During postnatal heart development, Ptpn23 interacts with sarcomeric α-actinin and coordinates the assembly of the DGC at costameres to sculpt T-tubule spatial patterning and morphology.

A meta-analysis was performed to compare the differences in outcomes between sutureless technique and conventional surgery for primary repair of Total Anomalous Pulmonary Venous Connection(TAPVC). Electronic databases, including PubMed, EMbase, Medline, CNKI, Wanfang Data and Weipu Data were searched systematically for the literature aimed mainly at comparing the therapeutic effects for primary repair of TAPVC administered by sutureless technique and conventional surgery. Corresponding data sets were extracted and two reviewers independently assessed the methodological quality. Seven studies meeting the inclusion criteria were included, involving a total of 1293 subjects. It was observed that sutureless technique entailed a lower occurrence rate of post-operative Pulmonary Veins Obstruction (PVO) (OR, 0.52 95%CI, 0.32–0.86; P = 0.01) and re-operation due to PVO (OR, 0.28;95%CI, 0.09–0.87; P = 0.03). However, meta-analyses of hospitalization time (WMD, 5.92; 95%CI, − 7.97-19.80; P = 0.40) and post-operative mortality (OR, 0.65; 95%CI, 0.41–1.04; P = 0.07) showed no significant differences between sutureless technique and conventional surgery. Meta-analysis of Cardiopulmonary Bypass (CPB) time and aortic cross-clamp time also showed no significant differences between the two surgical approaches (WMD, 5.07; 95%CI, − 9.29-19.42; P = 0.49); (WMD, 5.73; 95%CI, − 7.76-19.23; P = 0.40), but the result remained inconclusive due to pooling result changes after sensitivity analysis. Compared with conventional surgery, a lower occurrence rate of post-operative PVO and re-operation due to PVO were associated with sutureless technique. Meanwhile, hospitalization time and post-operative mortality were not statistically different between the two surgical approaches. Pooling result of CPB and aortic cross-clamp time between the two groups remained inconclusive.

A complete and prompt cardiac arrest using a cold cardioplegic solution is routinely used in heart transplantation to protect the graft function. However, warm ischemic time is still inevitable during the procedure to isolate donor hearts in the clinical setting. Our knowledge of the mechanism changes prevented by cold storage, and how warm ischemia damages donor hearts, is extremely poor. The potential consequences of this inevitable warm ischemic time to grafts, and the underlying potential protective mechanism of prompt graft cooling, have been studied in order to explore an advanced graft protection strategy. To this end, a surgical procedure, including 10–15 min warm ischemic time during procurement, was performed in mouse models to mimic the clinical situation (Group I), and compared to a group of mice that had the procurement performed with prompt cooling procedures (Group II). The myocardial morphologic changes (including ultrastructure) were then assessed by electron and optical microscopy after 6 h of cold preservation. Furthermore, syngeneic heart transplantation was performed after 6 h of cold preservation to measure the graft heart function. An electron microscopy showed extensive damage, including hypercontracted myofibers with contraction bands, and damaged mitochondria that released mitochondrial contents in Group I mice, while similar patterns of damage were not observed in the mice from Group II. The results from both the electron microscopy and immunoblotting verified that cardiac mitophagy (protective mitochondrial autophagy) was present in the mice from Group II, but was absent in the mice from Group I. Moreover, the mice from Group II demonstrated faster rebeating times and higher beating scores, as compared to the mice from Group I. The pressure catheter system results indicated that the graft heart function was significantly more improved in the mice from Group II than in those from Group I, as demonstrated by the left ventricle systolic pressure (31.96 ± 6.54 vs. 26.12 ± 8.87 mmHg), the +dp/dt (815.6 ± 215.4 vs. 693.9 ± 153.8 mmHg/s), and the -dp/dt: (492.4 ± 92.98 vs. 418.5 ± 118.9 mmHg/s). In conclusion, the warm ischemic time during the procedure impaired the graft function and destroyed the activation of mitophagy. Thus, appropriate mitophagy activation has emerged as a promising therapeutic target that may be essential for graft protection and functional improvement during heart transplantation.