Infections, atherosclerosis, and coronary heart disease.

Atherosclerosis is a chronic inflammatory disease. Pathophysiological similarities between chronic infections and atherosclerosis triggered interest in a clinical association between these conditions. Various infectious microbes have been linked to atherosclerotic vascular disease in epidemiological studies. However, this association failed to satisfy the Koch's postulates of causation with multiple clinical trials demonstrating inefficacy of anti-infective therapies in mitigating atherosclerotic cardiovascular events. Identification of underlying pathophysiological mechanisms and experience with vaccination against various infectious agents has ushered a new avenue of efforts in the development of an anti-atherosclerotic vaccine. Studies in animal models have identified various innate and adaptive immune pathways in atherosclerosis. In this review, we discuss the patho-biological link between chronic infections and atherosclerosis, evaluate existing evidence of animal and human trials on the association between infections and cardiovascular disease and introduce the concept of an anti-atherosclerotic vaccine

PCSK9 and inflammation: Role of shear stress, pro-inflammatory cytokines and LOX-1 4

PCSK9 degrades LDL receptors and subsequently increases serum LDL-cholesterol. Clinical trials show that inhibition of PCSK9 efficiently lowers LDL-cholesterol levels and reduces cardiovascular events. PCSK9 inhibitors also reduce the extent of atherosclerosis. Recent studies show that PCSK9 is secreted by vascular endothelial cells, smooth muscle cells and macrophages. PCSK9 induces secretion of pro-inflammatory cytokines in macrophages, liver cells, and in a variety of tissues. PCSK9 regulates TLR4 expression and NF-κB activation as well as development of apoptosis and autophagy. PCSK9 also interacts with oxidized-LDL receptor-1 (LOX-1) in a mutually facilitative fashion. These observations suggest that PCSK9 is inter-twined with inflammation with implications in atherosclerosis and its major consequence - myocardial ischemia. This relationship provides a basis for the use of PCSK9 inhibitors in prevention of atherosclerosis and related clinical events

In-hospital complications associated with pulmonary vein isolation with adjunctive lesions: the NCDR AFib Ablation Registry

AimsNo prior study has been adequately powered to evaluate real-world safety outcomes in those receiving adjunctive ablation lesions beyond pulmonary vein isolation (PVI). We sought to evaluate characteristics and in-hospital complications among patients undergoing PVI with and without adjunctive lesions.Methods and resultsPatients in the National Cardiovascular Data Registry AFib Ablation Registry undergoing first-time atrial fibrillation (AF) ablation between 2016 and 2020 were identified and stratified into paroxysmal (PAF) and persistent AF, and separated into PVI only, PVI + cavotricuspid isthmus (CTI) ablation, and PVI + adjunctive (superior vena cava isolation, coronary sinus, vein of Marshall, atypical atrial flutter lines, other). Adjusted odds of adverse events were calculated using multivariable logistic regression. A total of 50 937 patients [PAF: 30 551 (60%), persistent AF: 20 386 (40%)] were included. Among those with PAF, there were no differences in the adjusted odds of complications between PVI + CTI or PVI + adjunctive when compared with PVI only. Among persistent AF, PVI + adjunctive was associated with a higher risk of any complication [3.0 vs. 4.5%, odds ratio (OR) 1.30, 95% confidence interval (CI) 1.07-1.58] and major complication (0.8 vs. 1.4%, OR 1.56, 95% CI 1.10-2.21), while no differences were observed in PVI + CTI compared with PVI only. Overall, there was high heterogeneity in adjunctive lesion type, and those receiving adjunctive lesions had a higher comorbidity burden.ConclusionAdditional CTI ablation was common without an increased risk of complications. Adjunctive lesions other than CTI are commonly performed in those with more comorbidities and were associated with an increased risk of complications in persistent AF, although the current analysis is limited by high heterogeneity in adjunctive lesion set type

Amiodarone use and all-cause mortality in patients with a continuous-flow left ventricular assist device

Background Atrial and ventricular arrhythmias are commonly encountered in patients with advanced heart failure, with amiodarone being the most commonly used antiarrhythmic drug in continuous-flow left ventricular assist device (CF-LVAD) recipients. The purpose of this study was to assess the impact of amiodarone use on long-term all-cause mortality in ptients with a CF-LVAD. Methods and Results A retrospective multicenter study of CF-LVAD was conducted at 5 centers including all CF-LVAD implants from 2007 to 2015. Patients were stratified based on pre-CF-LVAD implant amiodarone use. Additional use of amiodarone after CF-LVAD implantation was also evaluated. Primary outcome was all-cause mortality during long-term follow-up. Kaplan-Meier curves were used to assess survival outcomes. Multivariable Cox regression was used to identify predictors of outcomes. Propensity matching was done to address baseline differences. A total of 480 patients with a CF-LVAD (aged 58±13 years, 81% men) were included. Of these, 170 (35.4%) were on chronic amiodarone therapy at the time of CF-LVAD implant, and 310 (64.6%) were not on amiodarone. Rate of all-cause mortality over the follow-up period was 32.9% in the amiodarone group compared with 29.6% in those not on amiodarone (=0.008). Similar results were noted in the propensity-matched group (log-rank, =0.04). On multivariable Cox regression analysis, amiodarone use at baseline was independently associated with all-cause mortality (hazard ratio, 1.68 [95% CI, 1.1-2.5]; =0.01). Conclusions Amiodarone use was associated with significantly increased rates of all-cause mortality in CF-LVAD recipients. Earlier interventions for arrhythmias to avoid long-term amiodarone exposure may improve long-term outcomes in CF-LVAD recipients and needs further study