Overlapping pandemics of lifestyle-related diseases pose a substantial threat to cardiovascular health. Apart from coronary artery disease, metabolic disturbances linked to obesity, insulin resistance and diabetes directly compromise myocardial structure and function through independent and shared mechanisms heavily involving inflammatory signals. Accumulating evidence indicates that metabolic dysregulation causes systemic inflammation, which in turn aggravates cardiovascular disease. Indeed, elevated systemic levels of pro-inflammatory cytokines and metabolic substrates induce an inflammatory state in different cardiac cells and lead to subcellular alterations thereby promoting maladaptive myocardial remodeling. At the cellular level, inflammation-induced oxidative stress, mitochondrial dysfunction, impaired calcium handling, and lipotoxicity contribute to cardiomyocyte hypertrophy and dysfunction, extracellular matrix accumulation and microvascular disease. In cardiometabolic patients, myocardial inflammation is maintained by innate immune cell activation mediated by pattern recognition receptors such as Toll-like receptor 4 (TLR4) and downstream activation of the NLRP3 inflammasome and NF-κB-dependent pathways. Chronic low-grade inflammation progressively alters metabolic processes in the heart, leading to a metabolic cardiomyopathy (MC) phenotype and eventually to heart failure with preserved ejection fraction (HFpEF). In accordance with preclinical data, observational studies consistently showed increased inflammatory markers and cardiometabolic features in patients with HFpEF. Future treatment approaches of MC may target inflammatory mediators as they are closely intertwined with cardiac nutrient metabolism. Here, we review current evidence on inflammatory processes involved in the development of MC and provide an overview of nutrient and cytokine-driven pro-inflammatory effects stratified by cell type.

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Aims The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and its shedding product [soluble LOX-1 (sLOX-1)] are implicated in atherosclerotic cardiovascular disease (ASCVD) pathogenesis. Herein, we examined the relationship of sLOX-1 with both fatal events and plaque progression in patients with acute coronary syndromes (ACS). Methods and results Plasma sLOX-1 was assessed at baseline in ACS and chronic coronary syndrome (CCS) patients prospectively recruited in the multicentre SPUM-ACS study, with sex- and age-matched healthy subjects serving as additional controls (n = 2924). Compared with both CCS and controls, ACS patients showed markedly elevated sLOX-1 levels (median, 2.00 and 2.00 vs. 35.08 pg/mL; P < 0.0001) which were independently associated with increased mortality risk over 30-day [tertile (T)3: adjusted hazard ratio (HR), 3.11; 95% confidence interval (CI), 1.44–10.61; P = 0.0055] and 1-year intervals (T3: adjusted HR, 2.04; 95% CI, 1.19–3.92; P = 0.0098). Results remained consistent after adjustment for GRACE 2.0 (T3: adjusted HR, 1.86; 95% CI, 1.04–3.74; P = 0.0391) and were primarily driven by the pronounced relationship of sLOX-1 with cardiovascular mortality at 30 days (T3: adjusted HR, 3.81; 95% CI, 1.62–19.62; P = 0.0036) and at 1 year (T3: adjusted HR, 2.29; 95% CI, 1.19–5.34; P = 0.0148). In ACS patients undergoing serial intracoronary imaging and statin therapy, sLOX-1 dropped significantly in those with coronary plaque regression at 1 year (ΔsLOX-1: −4.64 ± 1.80; P = 0.0057), and showed a good discrimination for predicting plaque progression (area under the curve = 0.74; 95% CI, 0.59–0.86; P = 0.0031). Conclusion Plasma sLOX-1 levels are increased during ACS and predict fatal events beyond traditional and emerging risk factors. Persistently high sLOX-1 associates with coronary plaque progression in patients with established ASCVD. Clinical Trial Registration NCT01000701.

Objective: Traumatic arteriovenous fistulas (AVFs) are rare. The vast majority occur secondary to penetrating injuries. High-output cardiac failure is a well-recognized serious complication of AVFs, associated with high morbidity and mortality. The objective of the present study was to identify predictors of heart failure (HF) in patients with traumatic AVF.Methods: Both PubMed/MEDLINE (Ovid) and CINAHL were searched (up to June 2019) for studies reporting individual patient data on the clinical and demographic characteristics of patients with AVF secondary to penetrating trauma. Exclusion criteria were age <18 years, no specification of symptoms, a cranial, spinal, or cardiac AVF location, and an iatrogenic mechanism of injury. The present study was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines.Results: A total of 274 AVF patients from 15 case series and 177 case reports were included. The median age at presentation was 32 years (interquartile range, 24-43 years), 90% were men. The most frequent mechanisms of injury were stab wounds (43%) and gunshot wounds (32%). The AVF location was the abdomen (n ¼ 86; 31%), lower limb (n ¼ 79; 29%), neck (n ¼ 61; 22%), thorax (n ¼ 38; 14%), and upper limb (n ¼ 10; 4%). Of the 274 patients, 35 (13%) had presented with HF and 239 (87%) with other symptoms. The risk of HF increased with an increased feeding artery diameter (P < .001). On univariate analysis, HF was significantly associated with a longer median time from injury to presentation with AVF (11.2 years vs 0.1 years; P < .001), older median age at presentation (43 years vs 31 years; P ¼ .002), involvement of a large feeding artery (ie, aorta, pulmonary artery, subclavian artery, external iliac artery; 40% vs 13%; P < .001), shrapnel injuries (11% vs 2%; P ¼ .011), and injuries to the trunk or lower limb (94% vs 71%; P ¼ .004). After adjusting for clinical and demographic patient characteristics, involvement of a large feeding artery (odds ratio, 3.25; 95% confidence interval, 1.26-8.42; P ¼ .015) and every 6 years of delay to presentation (odds ratio, 1.30; 95% confidence interval, 1.03-1.63; P ¼ .026) remained independent predictors for HF.Conclusions: HF occurs in a small but important fraction of traumatic AVF patients and develops after highly variable latency periods. Large feeding arteries and delayed presentation independently predicted HF in this cohort.