Cardiac arrhythmias constitute a major health problem with a huge impact on mortality rates and health care costs. Despite ongoing research efforts, the understanding of the molecular mechanisms and processes responsible for arrhythmogenesis remains incomplete. Given the crucial role of Ca²⁺-handling in action potential generation and cardiac contraction, Ca²⁺ channels and Ca²⁺ handling proteins represent promising targets for suppression of ventricular arrhythmias. Accordingly, we report the different roles of Ca²⁺-handling in the development of congenital as well as acquired ventricular arrhythmia syndromes. We highlight the therapeutic potential of gene therapy as a novel and innovative approach for future arrhythmia therapy. Furthermore, we discuss various promising cellular and mitochondrial targets for therapeutic gene transfer currently under investigation.

Background: With the advent of implantable cardioverter-defibrillator (ICD) technology in recent decades, patients with inherited or congenital cardiomyopathy have a greater chance of survival into adulthood. Women with ICDs in this group are now more likely to reach reproductive age. However, pregnancy represents a challenge for clinicians, as no guidelines for the treatment of pregnant women with an ICD are currently available. Methods: To analyze this issue, we performed a systematic screening of the literature using the keywords: pregnancy with ICD, lead fracture in pregnancy, lead thrombi in pregnancy, ventricular tachycardia in pregnancy, inappropriate shocks in pregnancy, ICD discharge in pregnancy and ICD shock in pregnancy. Of 1101 publications found, 27 publications were eligible for further analysis (four retrospective trials and 23 case reports). Results: According to physiological changes in pregnancy, resulting in an increase in heart rate and cardiac output, a vulnerability for malignant arrhythmias and device-related complications in ICD carriers might be suspected. While the literature is limited on this issue, maternal complications including arrhythmia burden with following ICD therapies, thromboembolic events and lead complications as well as inappropriate shock therapy have been reported. According to the limited available studies, associated risk seems not to be more frequent than in the general population and depends on the underlying cardiac pathology. Furthermore, worsening of heart failure and related cardiovascular disease have been reported with associated risk of preterm delivery. These observations are exaggerated by restricted applications of diagnostics and treatment due to the risk of fetal harm in this population. Conclusions: Due to limited data on management of ICDs during pregnancy, further scientific investigations are required. Consequently, careful risk assessment with individual risk evaluation and close follow ups with interdisciplinary treatment are recommended in pregnant ICD carriers.

Background: Gender-specific differences in the outcome of COVID-19 patients requiring intensive care treatment have been reported. However, a potential association with ICU therapy remains elusive. Methods: A total of 224 consecutive patients (63 women) treated for severe COVID-19 disease requiring mechanical ventilation were screened for the study. After propensity score matching for gender, 40 men and 40 women were included in the study. Comparative analysis was conducted for laboratory parameters, ICU therapy and complications (pulmonary embolism, thrombosis, stroke, and ventricular arrhythmias), and outcome (mortality). Results: Male patients had significantly higher levels of CRP (p = 0.012), interleukin-6 (p = 0.020) and creatinine (p = 0.027), while pH levels (p = 0.014) were significantly lower compared to females. Male patients had longer intubation times (p = 0.017), longer ICU stays (p = 0.022) and higher rates of catecholamine dependence (p = 0.037). Outcome, complications and ICU therapy did not differ significantly between both groups. Conclusion: The present study represents the first matched comparison of male and female COVID-19 patients requiring intensive care treatment. After propensity matching, male patients still displayed a higher disease severity. This was reflected in higher rates of vasopressors, duration of ICU stay and duration of intubation. In contrast, no significant differences were observed in mortality rates, organ replacement therapy and complications during ICU stay.

In this retrospective single-center trial, we analyze 109 consecutive patients (female: 27.5%, median age: 69 years, median left ventricular ejection fraction: 20%) who survived sudden cardiac death (SCD) and needed hemodynamic support from an Impella assist device between 2008 and 2018. Rhythm monitoring is investigated in this population and associations with hospital survival are analyzed. Hospital mortality is high, at 83.5%. Diverse cardiac arrhythmias are frequently registered during Impella treatment. These include atrial fibrillation (AF, 21.1%) and ventricular tachycardia (VT, 18.3%), as well as AV block II°/III° (AVB, 7.3%), while intermittent asystole (ASY) is the most frequently observed arrhythmia (42.2%). Nevertheless, neither ventricular nor supraventricular tachycardias are associated with patients’ survival. In patients who experience intermittent asystole, a trend towards a fatal outcome is noted (p = 0.06). Conclusions: Mortality is high in these severely sick patients. While cardiac arrhythmias were frequent, they did not predict hospital mortality in this population. The hemodynamic support of the pump seems to counterbalance the adverse effects of these events.