ErbB2 interacting protein (Erbin) is a widely expressed protein and participates in inhibition of several intracellular signaling pathways. Its mRNA has been found to be present in relatively high levels in the heart. However, its physiological role in the heart has not been explored. In the present work, we elucidated the role of Erbin in cardiac hypertrophy. Cardiac hypertrophy was induced in mice either by isoproterenol administration or by aortic constriction. The level of Erbin was significantly decreased in both models. Erbin^−/− mice rapidly develop decompensated cardiac hypertrophy, and following severe pressure overload all Erbin^−/− mice died from heart failure. Down-regulation of Erbin expression was also observed in biopsies derived from human failing hearts. It is known that Erbin inhibits Ras-mediated activation of the extracellular signal-regulated kinase (ERK) by binding to Soc-2 suppressor of clear homolog (Shoc2). Our data clearly show that ERK phosphorylation is enhanced in the heart tissues of Erbin^−/− mice. Furthermore, we clearly demonstrate here that Erbin associates with Shoc2 in both whole hearts and in cardiomyocytes, and that in the absence of Erbin, Raf is phosphorylated and binds Shoc2, resulting in ERK phosphorylation. In conclusion, Erbin is an inhibitor of pathological cardiac hypertrophy, and this inhibition is mediated, at least in part, by modulating ERK signaling.

BACKGROUND: Over the past 25 years, diagnosis and therapy for acute aortic dissection (AAD) have evolved. We aimed to study the effects of these iterative changes in care. METHODS: Patients with nontraumatic AAD enrolled in the International Registry of Acute Aortic Dissection (61 centers; 15 countries) were divided into time-based tertiles (groups) from 1996 to 2022. The impact of changes in diagnostics, therapeutic care, and in-hospital and 3-year mortality was assessed. Cochran-Armitage trend and Jonckheere-Terpstra tests were conducted to test for any temporal trend. RESULTS: Each group consisted of 3785 patients (mean age, ≈62 years old; ≈65.5% males); nearly two-thirds had type A AAD. Over time, the rates of hypertension increased from 77.8% to 80.4% ( P =0.002), while smoking (34.1% to 30.6%, P =0.033) and atherosclerosis decreased (25.6%–16.6%; P <0.001). Across groups, the percentage of surgical repair of type A AAD increased from 89.1% to 92.5% ( P <0.001) and was associated with decreased hospital mortality (from 24.1% in group 1 to 16.7% in group 3; P <0.001). There was no difference in 3-year survival ( P =0.296). For type B AAD, stent graft therapy (thoracic endovascular aortic repair) was used more frequently (22.3%–35.9%; P <0.001), with a corresponding decrease in open surgery. Endovascular in-hospital mortality decreased from 9.9% to 6.2% ( P =0.003). As seen with the type A AAD cohort, overall 3-year mortality for patients with type B AAD was consistent over time ( P =0.084). CONCLUSIONS: Over 25 years, substantial improvements in-hospital survival were associated with a more aggressive surgical approach for patients with type A AAD. Open surgery has been partially supplanted by thoracic endovascular aortic repair for complicated type B AAD, and in-hospital mortality has decreased over the time period studied. Postdischarge survival for up to 3 years was similar over time.

With the improvement in survival rate, cardiotoxicity has emerged as a significant adverse effect of cancer therapy. Early diagnosis of subclinical cardiac injury may allow the initiation of cardioprotective therapy and preventing the interruption of optimal cancer therapy and the development of irreversible cardiac dysfunction. In this article, we review the role of two-dimensional speckle tracking echocardiography (2D-STE), beyond the common left ventricle global longitudinal strain in the diagnosis of early subclinical cardiac injury in patients treated with cancer therapies.

Recent years have brought major advancements in the use of immune therapy and specifically immune checkpoint inhibitors (ICIs) in cancer patients, with expanding indications for various malignancies resulting in the treatment of a large and increasing number of patients. While this therapy significantly improves outcomes in a variety of hematologic and solid tumors, the use of ICIs is associated with a substantial risk of immune-related adverse events. Cardiovascular toxicity, while not the most common side effect of ICIs, is associated with significant morbidity and mortality. It is therefore crucial for oncologists and cardiologists, as well as internists and emergency room physicians, to have a good understanding of this increasingly common clinical problem. In the present review, we discuss the cardiac aspects of ICI therapy with special emphasis on the clinical manifestations of their cardiovascular toxicity, diagnostic approaches, treatment and suggested surveillance.