Arrhythmogenic cardiomyopathy (AC) is a heritable, potentially lethal disease without a causal therapy. AC is characterized by focal cardiomyocyte death followed by inflammation and progressive formation of connective tissue. The pathomechanisms leading to structural disease onset and progression, however, are not fully elucidated. Recent studies revealed that dysregulation of autophagy and endoplasmic/sarcoplasmic reticulum (ER/SR) stress plays an important role in cardiac pathophysiology. We therefore examined the temporal and spatial expression patterns of autophagy and ER/SR stress indicators in murine AC models by qRT-PCR, immunohistochemistry, in situ hybridization and electron microscopy. Cardiomyocytes overexpressing the autophagy markers LC3 and SQSTM1/p62 and containing prominent autophagic vacuoles were detected next to regions of inflammation and fibrosis during onset and chronic disease progression. mRNAs of the ER stress markers Chop and sXbp1 were elevated in both ventricles at disease onset. During chronic disease progression Chop mRNA was upregulated in right ventricles. In addition, reduced Ryr2 mRNA expression together with often drastically enlarged ER/SR cisternae further indicated SR dysfunction during this disease phase. Our observations support the hypothesis that locally altered autophagy and enhanced ER/SR stress play a role in AC pathogenesis both at the onset and during chronic progression.

The early initiation of cardiopulmonary resuscitation (CPR) measures by non-professionals before the arrival of Emergency Medical Service (EMS) is known to be crucial for improving outcomes after out-of-hospital cardiac arrest (OHCA). We assessed the impact of deploying CPR-trained volunteers via a smartphone-based alerting system on the outcome of OHCA patients. In a retrospective nonrandomized cohort study, all OHCA cases in the city of Aachen over a six-year period were analysed. We compared patient data, CPR metrics, alerting system data as well as outcome data between the intervention and control groups. From June 2017 to May 2023, 101 out of 852 resuscitations were initiated by volunteers alerted via a smartphone-based alerting system in OHCA events. We found no overall rise in the return of spontaneous circulation (ROSC) rate. An age-dependent subgroup analysis indicated an increased incidence of initially shockable rhythms and an increased ROSC rate for patients younger than 60 years in the intervention group, while implying a lower ROSC rate in patients older than 80 years after mobile responder CPR. Although this study was underpowered to yield statistically significant results, our findings suggest the need for an age-sensitive approach when evaluating the effects of first-responder systems on OHCA cases.