Case Report: Hypertrophic cardiomyopathy with recurrent episodes of ventricular fibrillation and concurrent sinus arrest

BackgroundHypertrophic cardiomyopathy (HCM) is a serious hereditary cardiomyopathy. It is characterized morphologically by an increased left ventricular wall thickness and mass and functionally by enhanced global chamber function and myocellular contractility, diastolic dysfunction, and myocardial fibrosis development. Typically, patients with HCM experience atrial fibrillation (AF), syncope, and ventricular fibrillation (VF), causing severe symptoms and cardiac arrest. In contrast, sinoatrial node (SAN) arrest in the setting of HCM is uncommon. In particular, during VF, it has not been described so far.Case summaryIn this study, we report an 18-year-old woman patient with sudden cardiac arrest due to VF and successful cardiopulmonary resuscitation as the first clinical manifestation of non-obstructive HCM. Subsequently, a subcutaneous implantable cardioverter-defibrillator (ICD) was implanted for secondary VF prophylaxis. However, additional episodes of VF occurred. During these, device interrogation revealed a combined occurrence of VF, bradycardia, and SAN arrest, requiring a device exchange into a dual-chamber ICD. A heterozygous, pathogenic variant of the MYH7 gene (c.2155C>T; p.Arg719Trp) was identified as causative for HCM.DiscussionFirst published in 1994, the particular MYH7 variant (p.Arg719Trp) was described in HCM patients with a high incidence of premature cardiac death and a reduced life expectancy. Electrophysiological studies on HCM patients are mainly performed to treat AF and ventricular tachycardia. Further extraordinary arrhythmic phenotypes were reported only in a few HCM patients. Taken together, the present case with documented co-existing VF and SAN arrest is rare and also emphasizes addressing the presence of SAN arrest (in particular, during VF episodes) in HCM patients when a distinct ICD device is considered for implantation

Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells

Höving AL, Schmidt KE, Merten M, et al. Blood Serum Stimulates p38-Mediated Proliferation and Changes in Global Gene Expression of Adult Human Cardiac Stem Cells. Cells. 2020;9(6): 1472.During aging, senescent cells accumulate in various tissues accompanied by decreased regenerative capacities of quiescent stem cells, resulting in deteriorated organ function and overall degeneration. In this regard, the adult human heart with a generally low regenerative potential is of extreme interest as a target for rejuvenating strategies with blood borne factors that might be able to activate endogenous stem cell populations. Here, we investigated for the first time the effects of human blood plasma and serum on adult human cardiac stem cells (hCSCs) and showed significantly increased proliferation capacities and metabolism accompanied by a significant decrease of senescent cells, demonstrating a beneficial serum-mediated effect that seemed to be independent of age and sex. However, RNA-seq analysis of serum-treated hCSCs revealed profound effects on gene expression depending on the age and sex of the plasma donor. We further successfully identified key pathways that are affected by serum treatment with p38-MAPK playing a regulatory role in protection from senescence and in the promotion of proliferation in a serum-dependent manner. Inhibition of p38-MAPK resulted in a decline of these serum-mediated beneficial effects on hCSCs in terms of decreased proliferation and accelerated senescence. In summary, we provide new insights in the regulatory networks behind serum-mediated protective effects on adult human cardiac stem cells

Blood serum stimulates p38-mediated proliferation and changes in global gene expression of adult human cardiac stem cells

During aging, senescent cells accumulate in various tissues accompanied by decreased regenerative capacities of quiescent stem cells, resulting in deteriorated organ function and overall degeneration. In this regard, the adult human heart with a generally low regenerative potential is of extreme interest as a target for rejuvenating strategies with blood borne factors that might be able to activate endogenous stem cell populations. Here, we investigated for the first time the effects of human blood plasma and serum on adult human cardiac stem cells (hCSCs) and showed significantly increased proliferation capacities and metabolism accompanied by a significant decrease of senescent cells, demonstrating a beneficial serum-mediated effect that seemed to be independent of age and sex. However, RNA-seq analysis of serum-treated hCSCs revealed profound effects on gene expression depending on the age and sex of the plasma donor. We further successfully identified key pathways that are affected by serum treatment with p38-MAPK playing a regulatory role in protection from senescence and in the promotion of proliferation in a serum-dependent manner. Inhibition of p38-MAPK resulted in a decline of these serum-mediated beneficial effects on hCSCs in terms of decreased proliferation and accelerated senescence. In summary, we provide new insights in the regulatory networks behind serum-mediated protective effects on adult human cardiac stem cells