115 Prognostic significance of iron deficiency status in chronic inflammatory cardiomyopathy

Aims Iron deficiency (ID) and associated anaemia (IDA) represent major comorbidities in chronic diseases. However, their prevalence and prognostic significance have never been investigated in chronic inflammatory cardiomyopathy (CIC). Methods and results This is a single-centre, prospective study, on consecutive adult patients with CIC (symptom onset > 3 months, endomyocardial biopsy-proven chronic myocarditis) undergoing iron status assessment (enrollment: January 2014–January 2019). ID was defined as either serum ferritin < 100 µg/l or transferrin saturation < 20%. IDA was defined as haemoglobin < 12 g/dl in women, < 13 g/dl in men. The primary endpoint was the occurrence of heart failure events (HFE) and/or arrhythmic events (AE). The study cohort is composed by 219 CIC patients (mean age 46 ± 15 y, 71% males, mean LVEF 50 ± 14%). Diagnosis was furtherly supported by cardiac magnetic resonance in 194 cases (89%). Baseline characteristics of patients with IDA (n = 48), ID (n = 70), and non-ID controls (n = 101) were largely comparable. We found that median in-hospital stay length was 13 days (IQR: 6–20) in IDA patients vs. 8 (IQR: 5–11) in the remaining groups (P = 0.002), and was inversely correlated with haemoglobin values on admission. By 3.9 ± 1.8 year prospective follow-up, events occurred in 86 patients (39%). For the composite endpoint, the only factors associated with events were ID status (HR: 6.3, 95% CI: 2.1–19.5, P = 0.001) and male gender (HR: 5.4, 95% CI: 1.2–24.9, P = 0.030). In detail, HFE occurred in 48 patients (40/118 IDA or ID vs. 8/101 controls, P < 0.001), and AE in 51 (34/118 IDA or ID vs. 17/101 controls, P = 0.039). All cardiac deaths (n = 7) occurred in ID or IDA patients (P = 0.016; n = 1 and 6, respectively). Conclusions ID and IDA are common among CIC patients, and may bare a negative prognostic value. Our findings suggest a careful evaluation of haemoglobin levels and iron status, and call for further investigation on both pathophysiological and prognostic implications of ID and IDA among CIC patients.

Therapeutic role of Prostaglandin E2 receptor 4 stimulation in inflammatory cardiomyopathy

Background Prostaglandin E2 receptor 4 (EP4) plays a crucial role in inflammatory diseases. Inflammatory cardiomyopathy often leads to refractory heart failure. Purpose We aimed to evaluate the role of EP4 in the development of inflammatory cardiomyopathy. Methods Experimental autoimmune myocarditis (EAM) was induced by immunization with cardiac myosin in balb/c mice. EP4 selective antagonist (CJ-42794, Cayman Chemical: 30 mg/kg/day), EP4 selective agonist (20 mg/kg/day), both, or vehicle alone was daily administrated after the immunization. Cardiac function and dimensions were assessed by echocardiography. Blood pressure and heart rate were assessed with tail-cuff method. Cardiac inflammation and fibrosis were immunohistologically examined. Molecular examination was performed by RT-PCR and immunoblotting. Results Cardiac dysfunction and dilatation were worsened on day 21 in EP4 antagonist-treated group compared with in the vehicle-treated group, accompanied by an increase in cellular infiltration area (21.7±1.9 vs. 11.0±2.7%, P=0.0367, respectively). Conversely, cardiac dysfunction and dilatation were improved in EP4 agonist-treated group compared with in the vehicle-treated group (Left ventricular fractional shortening: 69±3% vs. 40±4%, P<0.0001; Left ventricular systolic dimension: 0.7±0.1mm vs. 1.9±0.3mm, P=0.0007; respectively). These parameters did not show significant differences between both-treated group and the vehicle-treated group. The protective effect of EP4 stimulation in EAM was also kept on day 56. Moreover, cardiac fibrosis area as well as mRNA expressions of Type III collagen and brain natriuretic peptide in the bulk hearts was significantly reduced on day 56 in EP4 agonist-treated group compared with in the vehicle-treated group (12.3±2.4% vs. 24.7±3.0%, P=0.0278, respectively). Cardiac expression of phosphorylated smad 2/3 protein as well as TGF-β1 mRNA did not show significant differences between the 2 groups, while cardiac expression of RORgammat protein, the master regulator of Th17 immunity was increased in the EP4 antagonist-treated group. Conclusions EP4 activation negatively regulated the induction of cardiac autoimmunity, which alleviated cardiac dysfunction, dilatation, and fibrosis. EP4 may be a therapeutic target for preventing the development of inflammatory cardiomyopathy. FUNDunding Acknowledgement Type of funding sources: None.

Myocarditis and Inflammatory Cardiomyopathy

Activation of the inflammatory system occurs in most patients with advanced heart failure, regardless of etiology, and contributes to the pathophysiological milieu and the progression of the disease. The term inflammatory cardiomyopathy (ICM) refers to a group of disorders for which an acute or chronic myocardial inflammation is the central cause of abnormal cardiac structure or impaired cardiac function. The most common cause of inflammatory cardiomyopathy is lymphocytic myocarditis, which is most usually triggered by a viral infection, and occasionally by other infectious agents. Rare causes of specific inflammatory cardiomyopathies include cardiac sarcoidosis, giant cell myocarditis and eosinophilic myocarditis. Inflammatory cardiomyopathy can also occur in connection with autoimmune inflammatory diseases. Typical manifestations of inflammatory cardiomyopathy include chest pain, heart failure, and arrhythmias, but these symptoms and signs are unspecific. Although non-invasive diagnostic methods are emerging, the gold standard of diagnosis is the histological examination of an endomyocardial biopsy. Owing to the invasive nature of this technique and a modest diagnostic sensitivity, its use is limited. Therefore, the identification of inflammatory cardiomyopathy is elusive and the true incidence of the condition remains unknown. In most cases of lymphocytic myocarditis, recovery occurs within a few weeks following supportive treatment. In patients with cardiac sarcoidosis, giant cell myocarditis or eosinophilic myocarditis the use of immunosuppressive treatment is recommended, as is the case in myocarditis associated with autoimmune disorders. Such interventions may also have beneficial effects in chronic viral myocarditis once the virus has been cleared. In severe cases, treatment with mechanical circulatory support and/or heart transplantation may be required. Randomized intervention trials including antiviral, immunomodulating, or immunosuppressive agents are lacking. Similarly, new molecular-based methods and therapies tailored to specific pathogeneses have a potential to improve diagnosis and outcomes in patients with inflammatory cardiomyopathy. Still, such techniques and interventions are to be evaluated in adequate randomized controlled studies.

Fatal Outcomes from COVID-19 in Diabetes Patients and its Management: Impact of Diabetes and Other Comorbidities on COVID-19

: Many studies have approved that COVID-19 disease was caused by Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), severe acute respiratory syndrome coronavirus-1(SARS-CoV-1), and has spread as an epidemic from across the world today. Initially, it affects the upper respiratory tract, induces viral infection in the lungs, and causes severe pneumonia in the COVID-19 infected patients. After the infection in the body, changes appear in other biomarkers in the body therby imbalancing the body response studied by the virus's pathophysiology. However, this infection starts comorbidity directly and indirectly in COVID-19 infected patients. During this period of infection, the immune system is also suppressed by the virus and initiates other diseases. The authors focus on the cardiovascular comorbidity study of COVID-19 in the current work. In the comorbidity study of COVID-19, the virus mainly affects hypertension patients. The risk factor of comorbidity of hypertension and cardiovascular disorder is 30.7%, and 11.9% with diabetes mellitus. In this study, we reveal the pathophysiology, treatment, and management of cardiovascular diseases, their risk factor, and medicine results on the COVID-19 infected patients. SARS-CoV-2 primarily targets ACE-2 receptors because this virus receives this receptor as a host for the cellular entry of the virus in the body, these shows down regulations in the maintenance of BP, and the body suffers from multi-organ failure. The other diseases related to CVS are Inflammatory cardiomyopathy, congestive heart failure, irregular heartbeat, embolism events, and Coronary infarction that also affect its pathophysiology.