Background: Acute fulminant myocarditis (AFM) is a serious disease that progresses rapidly, and leads to failing respiratory and circulatory systems. When medications fail to reverse the patient’s clinical course, extracorporeal membrane oxygenation (ECMO) is considered the most effective, supportive and adjunct strategy. In this paper we analyzed our experience in managing AFM with ECMO support. Methods: During October 2003 and February 2017, a total of 35 patients (≥18 years) were enrolled in the study. Twenty patients survived, and another 15 patients expired. General demographics, the hemodynamic condition, timing of ECMO intervention, and laboratory data were compared for the survival and non-survival groups. Univariate and multivariate Cox regression analyses were performed to identify the associations with in-hospital mortality following ECMO use in this situation. Results: The survival rate was 57.1% during the in-hospital period. The average age, gender, severity of the hemodynamic condition, and cardiac rhythm were similar between the survival and non-survival groups. Higher serum lactic acid (initial and 24 h later), higher peak cardiac biomarkers, higher incidence of acute kidney injury and the need for hemodialysis were noted in the non-survival group. Higher 24-h lactic acid levels and higher peak troponin-I levels were associated with in-hospital mortality. Conclusions: When ECMO was used for AFM, related cardiogenic shock and decompensated heart failure, higher peak serum troponin-I levels and 24-h serum lactic acid levels following ECMO use were independently associated with in-hospital mortality.

Objectives: To examine the impact of revascularization and associated clinical outcomes of chronic kidney disease (CKD) chronic total occlusion (CTO) and non-CKD CTO groups. Background: The influence of CKD on clinical outcomes after percutaneous coronary intervention (PCI) for CTO lesions is unknown, and there is no systemic review of this topic to date. Methods: We searched the PubMed, Embase, ProQuest, ScienceDirect, Cochrane Library, ClinicalKey, Web of Science, and ClinicalTrials Databases for articles published between 1 January 2010 and 31 March 2020. CKD was defined as estimated glomerular filtration rate of <60 mL/min/1.73 m² according to the Modification of Diet in Renal Disease formula. Data included demographics, lesion distributions, incidence of contrast-induced nephropathy (CIN), acute kidney injury (AKI), procedural success rate, mortality, and target lesion revascularization (TLR)/target vessel revascularization (TVR). Results: Six studies were ultimately included in this systematic review. A high prevalence (25.5%; range, 19.6–37.9%) of CKD was noted in the CTO population. In the non-CKD group, outcomes were better: less incidence of CIN or AKI (odds ratio (OR), 2.860; 95% confidence interval (CI), 1.775–4.608), higher procedural success rate (OR, 1.382; 95% CI, 1.036–1.843), and lower long-term mortality (OR, 4.502; 95% CI, 3.561–5.693). The incidence of TLR/TVR (OR, 1.118; 95% CI, 0.888–1.407) did not differ between groups. Conclusions: In the CKD CTO PCI population, a lower procedural success rate, a higher incidence of CIN or AKI, and higher in-hospital and long-term mortality rate were noted due to more complex lesions and more comorbidities. However, the incidence of TLR/TVR did not differ between groups.

Background: Impaired renal function is frequently observed in patients with heart failure and reduced ejection fraction (HFrEF). The differential effect of sacubitril/valsartan and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEIs/ARBs) on the clinical and renal outcomes in patients with HFrEF and chronic kidney disease (CKD) remains unknown. Aims: This study aimed to explore the differential effect of sacubitril/valsartan and ACEI/ARB on the clinical and renal outcomes as well as renal function over a 12-month follow-up period in HFrEF patients with and without CKD. Methods: Patients with HfrEF (LVEF ≤35%) and NYHA class ≥II were enrolled from the Chang Gung Research Database between 2017 and 2020. Baseline characteristics were compared between patients prescribed sacubitril/valsartan and ACEI/ARB. After propensity score matching, the following clinical and renal outcomes were compared between the two groups in patients with and without CKD over a 12-month follow-up period: acute kidney injury (AKI), emergent dialysis/renal death, HF hospitalization, cardiovascular mortality, and all-cause mortality. Results: This study enrolled 3735 HFrEF patients with a mean left ventricular EF of 27.56 ± 5.86%, who had been prescribed sacubitril/valsartan (N = 1708) or ACEI/ARB (N = 2027). After propensity score matching, the clinical and renal outcomes did not differ between the sacubitril/valsartan and ACEI/ARB groups in patients without CKD. In patients with CKD, the ACEI/ARB group had a significantly higher incidence of all-cause mortality than the sacubitril/valsartan group (14.89% vs. 10.50%; hazard ratio 1.46; 95% confidence interval 1.06–2.00; p = 0.02), and the incidence of AKI, HF hospitalization, and CV mortality did not differ between the two groups. Conclusions: Sacubitril/valsartan had a lower all-cause mortality compared to ACEI/ARB in symptomatic HFrEF patients with CKD. Further prospective randomized studies are warranted to confirm our findings.

A prominent circadian variation is present in atrial fibrillation (AF) attacks that may be related to the expression of circadian clock genes. Little is known about the expression of circadian clock genes in AF. We prospectively enrolled 73 patients who had received pacemaker implantation, in order to define the burden of atrial high-rate episodes (AHREs) accurately. AF was diagnosed clinically in 43 (59%) patients (15 with persistent AF and 28 with paroxysmal AF). The expression levels of circadian clock genes of peripheral blood leukocytes were checked. There were more males and patients with a larger left atrial (LA) size and lower expression levels of BMAL1, CRY2, NR1D1, NR1D2, PER2, RORA, RORC, and TIM genes in persistent AF group than in other groups. There was a significant correlation between higher AHRE burden and larger LA size and between higher AHRE burden and decreased expression of circadian clock genes in patients with AF. LA volume and the expression of CRY1, NR1D1, and RORA are significantly associated with AHRE burden. However, the underlying mechanism needs to be elucidated in further studies.

Background. Type 2 diabetes was associated with a higher risk for permanent pacemaker (PPM) treatment. The difference in cardiovascular outcomes between patients with and without diabetes receiving PPM treatment remains unexplored. Method. Between January 2003 and December 2017, 1742 patients receiving naïve PPM treatment comprised this retrospective cohort study and were categorized into two groups by the diagnosis of diabetes: group with diabetes ( $n=632$ , 36.3%) and group without diabetes ( $n=1110$ , 63.7%). The primary outcome was cardiovascular events including heart failure (HF) hospitalization and acute myocardial infarction (AMI). The secondary outcomes of this study included pacemaker infection, pacing-induced cardiomyopathy, cerebrovascular accident, cardiovascular mortality, and all-cause mortality. Propensity score matching (PSM) was applied to reduce selection bias between the study groups. Result. During a mean follow-up period of $7.8\pm 4.8$ years, 264 patients had a cardiovascular event. Before PSM, the incidence of cardiovascular events was higher in patients with diabetes compared to patients without diabetes (19.8% vs. 12.5%, $P<0.001$ ), and the incidences of pacing-induced cardiomyopathy, cardiovascular mortality, and all-cause mortality were all higher in patients with diabetes compared to patients without diabetes. After PSM, the incidence of cardiovascular events was higher in patients with diabetes compared to patients without diabetes (18.8% vs. 12.3%, $P=0.015$ ). The incidence of HF hospitalization was higher in patients with diabetes compared to patients without diabetes (15.3% vs. 10.2%, $P=0.037$ ), whereas the incidence of AMI did not differ between the two groups. Moreover, after PSM, patients with diabetes had higher cumulative incidences of pacing-induced cardiomyopathy and all-cause mortality compared to patients without diabetes. Conclusions. The prevalence of diabetes was over one-third of naïve PPM recipients of this cohort, and diabetes increased the risk of cardiovascular events in PPM recipients, especially for HF hospitalization.

The molecular and genetic mechanisms underlying left atrial (LA) enlargement and atrial fibrosis following right ventricular (RV) dependent pacing remain unclear. Our objective was to investigate genetic expressions in the LA of pigs subjected to RV pacing for atrioventricular block (AVB), as well as to identify the differential gene expressions affected by biventricular (BiV) pacing. We established an AVB pig model and divided the subjects into three groups: a sham control group, an RV pacing group, and a BiV pacing group. Differential expression genes (DEGs) analyses conducted through next-generation sequencing (NGS) and enrichment analyses were employed to identify genes with altered expression in the LA myocardium. The RV pacing group showed a significant increase in extracellular fibrosis in the LA myocardium compared to the control group. NGS analysis revealed suppressed expression of the sirtuin signaling pathway in the RV pacing group. Among the DEGs within this pathway, GADD45G was found to be downregulated in the RV pacing group and upregulated in the BiV pacing group. Remarkably, the BiV pacing group exhibited elevated levels of GADD45G protein. In our study, we observed significant downregulation of SIRT1 and GADD45G genes, which are associated with the sirtuin signaling pathway, in the LA myocardium of the RV pacing group when compared to the control group. Moreover, these genes, which were downregulated in the RV pacing group, displayed a noteworthy upregulation in the BiV pacing group when compared to the RV pacing group.