Heart transplantation is an uncommon treatment for unresectable and non-metastatic primary cardiac sarcomas, and the role of it is unclear. This study aims to offer a survival analysis of it. This study consists of 6 patients from our institution and 40 patients identified in a literature search who underwent heart transplantation for non-metastatic primary cardiac sarcomas. Seven patients with unresectable cardiac angiosarcoma who received palliative therapies at our institution were included for comparison. All the clinicopathologic data were collected, retrospectively reviewed and statistically analyzed. Among the 46 patients receiving heart transplantation for primary cardiac sarcomas, the overall median survival was 16 months (2–112 months). The most common histologic type receiving heart transplantation was angiosarcoma. Its median survival time after heart transplantation (n = 14) was much less than that of other histologic types (n = 31) (9 vs 36 months; P = 0.002), which means it was not different from the median survival of 8 months for patients (n = 7) receiving palliative therapies (P = 0.768). The patients with grade 2 cardiac sarcomas (n = 5) survived much longer after heart transplantations than patients with grade 3 tumors (n = 15) (mean survival: 85 vs 18 months; P = 0.006). Neoadjuvant or adjuvant chemotherapy didn’t provide survival benefits after heart transplantation. Cardiac angiosarcoma seems to be not the proper indication of heart transplantation. The role of heart transplantation in other histologic subtypes still remains undefined. Lower grade and less aggressive histologic subtypes benefit more from heart transplantation.

Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are the two primary etiologies of end-stage heart failure. However, there remains a dearth of comprehensive understanding the global perspective and the dynamics of the proteome and phosphoproteome in ICM and DCM, which hinders the profound comprehension of pivotal biological characteristics as well as differences in signal transduction activation mechanisms between these two major types of heart failure. We conducted high-throughput quantification proteomics and phosphoproteomics analysis of clinical heart tissues with ICM or DCM, which provided us the system-wide molecular insights into pathogenesis of clinical heart failure in both ICM and DCM. Both protein and phosphorylation expression levels exhibit distinct separation between heart failure and normal control heart tissues, highlighting the prominent characteristics of ICM and DCM. By integrating with omics results, Western blots, phosphosite-specific mutation, chemical intervention, and immunofluorescence validation, we found a significant activation of the PRKACA-GSK3β signaling pathway in ICM. This signaling pathway influenced remolding of the microtubule network and regulated the critical actin filaments in cardiac construction. Additionally, DCM exhibited significantly elevated mitochondria energy supply injury compared to ICM, which induced the ROCK1-vimentin signaling pathway activation and promoted mitophagy. Our study not only delineated the major distinguishing features between ICM and DCM but also revealed the crucial discrepancy in the mechanisms between ICM and DCM. This study facilitates a more profound comprehension of pathophysiologic heterogeneity between ICM and DCM and provides a novel perspective to assist in the discovery of potential therapeutic targets for different types of heart failure.

A rapid pacing-induced heart failure model is commonly used in developing dilated cardiomyopathy (DCM). Traditionally, the right ventricular lead was connected with a single chamber pacemaker specific for animals that had a high frequency. However, the pacemaker used in this model is commercially unavailable. We developed a "pacing bigeminal" method using a commercially available dual-chamber (DDD) pacemaker to achieve high-frequency pacing. Twenty beagles were assigned to group A (n = 10) (pacing bigeminal method) and group B (n = 10) (traditional method). Echocardiographic measurements and electrocardiograms were obtained at baseline, at two weeks of pacing, and at 4 weeks of end pacing. LV anterior wall cardiac samples were obtained at 2 weeks of pacing and 4 weeks of end pacing for myocardial microscopic evaluation. Clinical manifestation and exposure time were also observed. After pacing for 10.5 ± 2.3 (714) days, the beagles in group B experienced heart failure, whereas in group A, only 7.9 ± 2.5 (5-12) days (P < 0.05) were needed to reach heart failure. Both methods could induce wide QRS duration, heart rate elevation, and myocardial microscopic changes (P > 0.05). In conclusion, this pacing bigeminal-induced heart failure method is feasible and can induce heart failure faster than the traditional method, which makes it a promising alternative method.