Innate Immune Receptors, Key Actors in Cardiovascular Diseases

Cardiovascular diseases (CVDs) are the leading cause of death in the industrialized world. Most CVDs are associated with increased inflammation that arises mainly from innate immune system activation related to cardiac damage. Sustained activation of the innate immune system frequently results in maladaptive inflam- matory responses that promote cardiovascular dysfunction and remodeling. Much research has focused on determining whether some mediators of the innate immune system are potential targets for CVD therapy. The innate immune system has specific receptors—termed pattern recognition receptors (PRRs)—that not only recognize pathogen-associated molecular patterns, but also sense danger-associated molecular signals. Acti- vation of PRRs triggers the inflammatory response in different physiological systems, including the cardio- vascular system. The classic PRRs, toll-like receptors (TLRs), and the more recently discovered nucleotide- binding oligomerization domain-like receptors (NLRs), have been recently proposed as key partners in the progression of several CVDs (e.g., atherosclerosis and heart failure). The present review discusses the key findings related to the involvement of TLRs and NLRs in the progression of several vascular and cardiac diseases, with a focus on whether some NLR subtypes (nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing receptor 3 and nucleotide-binding oligomerization domain-containing protein 1) can be candidates for the development of new therapeutic strategies for several CVDs

Organized Atrial Tachycardias after Atrial Fibrillation Ablation

The efficacy of catheter-based ablation techniques to treat atrial fibrillation is limited not only by recurrences of this arrhythmia but also, and not less importantly, by new-onset organized atrial tachycardias. The incidence of such tachycardias depends on the type and duration of the baseline atrial fibrillation and specially on the ablation technique which was used during the index procedure. It has been repeatedly reported that the more extensive the left atrial surface ablated, the higher the incidence of organized atrial tachycardias. The exact origin of the pathologic substrate of these trachycardias is not fully understood and may result from the interaction between preexistent regions with abnormal electrical properties and the new ones resultant from radiofrequency delivery. From a clinical point of view these atrial tachycardias tend to remit after a variable time but in some cases are responsible for significant symptoms. A precise knowledge of the most frequent types of these arrhythmias, of their mechanisms and components is necessary for a thorough electrophysiologic characterization if a new ablation procedure is required

Organized Atrial Tachycardias after Atrial Fibrillation Ablation

The efficacy of catheter-based ablation techniques to treat atrial fibrillation is limited not only by recurrences of this arrhythmia but also, and not less importantly, by new-onset organized atrial tachycardias. The incidence of such tachycardias depends on the type and duration of the baseline atrial fibrillation and specially on the ablation technique which was used during the index procedure. It has been repeatedly reported that the more extensive the left atrial surface ablated, the higher the incidence of organized atrial tachycardias. The exact origin of the pathologic substrate of these trachycardias is not fully understood and may result from the interaction between preexistent regions with abnormal electrical properties and the new ones resultant from radiofrequency delivery. From a clinical point of view these atrial tachycardias tend to remit after a variable time but in some cases are responsible for significant symptoms. A precise knowledge of the most frequent types of these arrhythmias, of their mechanisms and components is necessary for a thorough electrophysiologic characterization if a new ablation procedure is required

Effectiveness of sacubitril–valsartan in cancer patients with heart failure

Aims Current guidelines recommend sacubitril/valsartan for patients with heart failure and reduced left ventricular ejection fraction (LVEF), but there is lack of evidence of its efficacy and safety in cancer therapy-related cardiac dysfunction (CTRCD). Our aim was to analyse the potential benefit of sacubitril/valsartan in patients with CTRCD. Methods and results We performed a retrospective multicentre registry (HF-COH) in six Spanish hospitals with cardiooncology clinics including all patients treated with sacubitril/valsartan. Demographic and clinical characteristics and laboratory and echocardiographic data were collected. Median follow-up was 4.6 [1; 11] months. Sixty-seven patients were included (median age was 63 ± 14 years; 64% were female, 87% had at least one cardiovascular risk factor). Median time from anti-cancer therapy to CTRD was 41 [10; 141] months. Breast cancer (45%) and lymphoma (39%) were the most frequent neoplasm, 31% had metastatic disease, and all patients were treated with combination antitumor therapy (70% with anthracyclines). Thirtynine per cent of patients had received thoracic radiotherapy. Baseline median LVEF was 33 [27; 37], and 21% had atrial fibrillation. Eighty-five per cent were on beta-blocker therapy and 76% on mineralocorticoid receptor antagonists; 90% of the patients were symptomatic NYHA functional class ≥II. Maximal sacubitril/valsartan titration dose was achieved in 8% of patients (50 mg b.i.d.: 60%; 100 mg b.i.d.: 32%). Sacubitril/valsartan was discontinued in four patients (6%). Baseline Nterminal pro-B-type natriuretic peptide levels (1552 pg/mL [692; 3624] vs. 776 [339; 1458]), functional class (2.2 ± 0.6 vs. 1.6 ± 0.6), and LVEF (33% [27; 37] vs. 42 [35; 50]) improved at the end of follow-up (all P values ≤0.01). No significant statistical differences were found in creatinine (0.9 mg/dL [0.7; 1.1] vs. 0.9 [0.7; 1.1]; P = 0.055) or potassium serum levels (4.5 mg/dL [4.1; 4.8] vs. 4.5 [4.2; 4.8]; P = 0.5). Clinical, echocardiographic, and biochemical improvements were found regardless of the achieved sacubitril–valsartan dose (low or medium/high doses). Conclusions Our experience suggests that sacubitril/valsartan is well tolerated and improves echocardiographic functional and structural parameters, N-terminal pro-B-type natriuretic peptide levels, and symptomatic status in patients with CTRCD.This study was funded by the Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades, Spain, and the EU—European Regional Development Fund, by means of a competitive call for excellence in research projects (PIE14/00066) as well as by the Spanish Cardiovascular Network (CIBERCV)

Identification of Volatile and Semi-Volatile Compounds in Polymeric Coatings Used in Metal Cans by GC-MS and SPME

Polymeric coatings are used as a protective layer to preserve food or beverage quality and protect it from corrosion and avoid a metallic taste. These types of materials can contain some chemicals that are susceptible to migrate to food and constitute a risk for consumers’ health. This study is focused on the identification of volatile and semi-volatile low molecular weight compounds present in polymeric coatings used for metal food and beverage cans. A method based on solid–liquid extraction followed by gas chromatography–mass spectrometry (GC-MS) was optimized for the semi-volatile compounds. Different solvents were tried with the aim of extracting compounds with different polarities. Furthermore, a method based on solid-phase microextraction (SPME) in headspace (HS) mode and gas chromatography coupled with mass spectrometry (HSSPME-GC-MS) was developed for the identification of potential volatile migrants in polymeric coatings. Some parameters such as extraction time, equilibrium temperature, or the type of fiber were optimized. Different compounds, including aldehydes such as octanal or nonanal, alcohols such as α-terpineol or 2-butoxyethanol, ethers, alkenes, or phthalic compounds, among others, were identified and confirmed with analytical standards both via SPME analysis as well after solvent extractionThis research was funded by the Ministerio de Ciencia, Innovación y Universidades, by the Fondo Europeo de Desarrollo Regional (FEDER), and by the Agencia Estatal de Investigación Ref. No. PGC2018-094518-B-I00 “MIGRACOATING” (MICIU/FEDER, UE). The authors are grateful to the Ministerio de Ciencia, Innovación y Universidades for the predoctoral fellowship (ref. PRE2019-088195) awarded to P.V.-L.; A.L.-C. is grateful for her grant Programa de axudas á etapa predoutoral da Xunta de Galicia (Consellería de Cultura, Educación e Ordenación Universitaria)S

Innate immune receptors, key actors in cardiovascular diseases

Cardiovascular diseases (CVDs) are the leading cause of death in the industrialized world. Most CVDs are associated with increased inflammation that arises mainly from innate immune system activation related to cardiac damage. Sustained activation of the innate immune system frequently results in maladaptive inflammatory responses that promote cardiovascular dysfunction and remodeling. Much research has focused on determining whether some mediators of the innate immune system are potential targets for CVD therapy. The innate immune system has specific receptors—termed pattern recognition receptors (PRRs)—that not only recognize pathogen-associated molecular patterns, but also sense danger-associated molecular signals. Activation of PRRs triggers the inflammatory response in different physiological systems, including the cardiovascular system. The classic PRRs, toll-like receptors (TLRs), and the more recently discovered nucleotide-binding oligomerization domain-like receptors (NLRs), have been recently proposed as key partners in the progression of several CVDs (e.g., atherosclerosis and heart failure). The present review discusses the key findings related to the involvement of TLRs and NLRs in the progression of several vascular and cardiac diseases, with a focus on whether some NLR subtypes (nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing receptor 3 and nucleotide-binding oligomerization domain-containing protein 1) can be candidates for the development of new therapeutic strategies for several CVDs

Growth Differentiation Factor 15 at 1 Month After an Acute Coronary Syndrome Is Associated With Increased Risk of Major Bleeding.

BACKGROUND: Growth differentiation factor-15 (GDF-15) is related to major bleeding when measured at initial presentation in patients with acute coronary syndromes (ACSs) treated with dual antiplatelet therapy. It is unknown whether follow-up measurements provide additional information. The objective of this study was to investigate whether GDF-15 measured 1 month after an ACS provides additional information beyond the baseline levels with regard to the risk of major bleeding. METHODS AND RESULTS: GDF-15 was measured at baseline and at 1 month after an ACS in 4049 patients included in the PLATelet inhibition and patient Outcomes (PLATO) trial. The association between 1-month GDF-15 level and non-coronary artery bypass grafting surgery-related major bleeding was assessed by a multivariable Cox model, adjusting for baseline GDF-15, age, anemia, impaired renal function, history of gastrointestinal bleeding, and sex. Elevated GDF-15 (>1800 ng/L) at 1 month was associated with an increased risk of non-coronary artery bypass grafting-related major bleeding (3.9% versus 1.2%; hazard ratio, 3.38; 95% CI, 1.89-6.06), independent of baseline GDF-15. Patients who had elevated GDF-15 levels at baseline and subsequent nonelevated GDF-15 at 1 month had a similar risk as patients who had nonelevated levels at both measurements. CONCLUSIONS: GDF-15 at 1 month after an ACS is related to the risk of bleeding during DAPT and provides additional information on the bleeding risk beyond baseline GDF-15 levels. GDF-15 levels may therefore be useful as part of decision support concerning long-term antithrombotic treatment in patients post-ACS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872