"Real-world" analysis of battery longevity of implantable cardioverter-defibrillators: an in-depth analysis of a prospective defibrillator database.

BACKGROUND: There is a lack of evidence regarding contemporary implantable cardioverter-defibrillator (ICD) battery longevity. Our aim was to assess battery longevity in ICDs in a real-world setting. METHODS: Retrospective cross-sectional single center study of a prospectively collected database of consecutive patients who underwent ICD implantation from January 2010 to December 2015. Clinical data and battery longevity of all manufacturers were collected. RESULTS: A total of 351 patients (84.6% males, mean age of 61 ± 12 years) were included in the study (292 VVI; 6 VDD; 53 DDD). All manufacturers (Abbott, Biotronik, Boston, Medtronic and Microport) were equally represented in the study (p = 0.110). Median battery longevity was 10.8 years (11 years for VVI and 8.5 for DDD). After a follow-up time of 5 years, 98% of VVI and DDD were still in service (vs. industry-projected longevity of 98%). During this time, 89 patients (25.4%) underwent device replacement - 69 patients (77.5%) due to battery depletion, 6 patients due to infection, 3 patients due to dysfunction and 13 patients due to upgrade to CRT-D. Patients with Medtronic or Biotronik ICDs had a greater probability of being replaced earlier due to battery depletion (Biotronik HR 6.87, 95% CI 2.54-18.58, p < 0.001; Medtronic HR 6.08, 95% CI 2.45-15.06 p < 0.001). CONCLUSIONS: VVI and DDD ICD battery longevity matched industry-projected longevity after 5 years of follow-up. Medtronic and Biotronik ICDs appeared to have an earlier battery depletion. Further randomized studies are required to ensure optimal care.

Digoxin in Patients With Advanced Heart Failure and Sinus Rhythm Submitted to Cardiac Resynchronization Therapy-Is There Any Benefit?

ABSTRACT: Digoxin (DG) use in patients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm remains controversial. We aimed to assess the prognostic effect of DG in patients in sinus rhythm submitted to cardiac resynchronization therapy (CRT). Retrospective study including 297 consecutive patients in sinus rhythm, with advanced HFrEF submitted to CRT. Patients were divided into 2 groups: with DG and without DG (NDG). During a mean follow-up of 4.9 ± 3.4 years, we evaluated the effect of DG on the composite end point defined as cardiovascular hospitalization, progression to heart transplantation, and all-cause mortality. Previous to CRT, 104 patients (35%) chronically underwent DG and 193 patients (65%) underwent NDG treatment. The 2 groups did not differ significantly regarding HF functional class, HF etiology, QRS, and baseline left ventricular ejection fraction. The proportion of responders to CRT was similar in both groups (54% in DG vs. 56% in NDG; P = 0.78). During the long-term follow-up period, the primary end point occurred in a higher proportion in DG patients (67 vs. 48%; P = 0.002). After adjustment for potential confounders, DG use remained as an independent predictor of the composite end point of CV hospitalization, heart transplantation, and all-cause mortality [hazards ratio = 1.58; confidence interval, 95 (1.01-2.46); P = 0.045]. In conclusion, in patients in sinus rhythm with HFrEF submitted to CRT, DG use was associated with CV hospitalization, progression to heart transplant, and all-cause mortality.

Dietary Arthrospira platensis improves systemic antioxidant potential and changes plasma lipids without affecting related hepatic metabolic pathways in post-weaned piglets.

BACKGROUND: The ability of a high level of dietary Arthrospira platensis, individually or in combination with two exogenous carbohydrate-degrading enzymes (lysozyme and Rovabio®), to improve systemic antioxidant potential and hepatic lipid metabolism was tested in piglets. Forty male post-weaned piglets, sons of Large White × Landrace sows crossed with Pietrain boars, were allocated into 4 groups (n = 10) and fed during 28 days one of the following diets: 1) a control basal diet (cereal and soybean meal); 2) a basal diet with 10% of A. platensis (AP); 3) the AP diet supplemented with 0.005% of Rovabio® (AP + R); 4) the AP diet supplemented with 0.01% of lysozyme (AP + L). RESULTS: Arthrospira platensis decreased BW gain of piglets, regardless the addition of feed enzymes. The majority of plasma metabolites were affected by diets. A. platensis increased total lipids, total cholesterol and LDL-cholesterol, without changing hepatic fatty acid content or modulating, in an expressive manner, the transcriptional profile of lipid sensitive mediators. The antioxidant potential in general, and total carotenoids in particular, were improved by the microalga, regardless lysozyme or Rovabio®. CONCLUSIONS: Summing up, A. platensis, individually and combined with feed enzymes, impacts negatively on piglets' growth but improves the systemic antioxidant potential and changes plasma lipids with a minor modulation on related hepatic metabolic pathways.

Effect of dietary inclusion of Spirulina on production performance, nutrient digestibility and meat quality traits in post-weaning piglets.

The effect of Spirulina (Arthrospira platensis), individually or in combination with two commercial carbohydrases, in piglet diets was assessed on growth performance, nutrient digestibility and meat quality traits. Forty post-weaned male piglets from Large White × Landrace sows crossed with Pietrain boars with an initial live weight of 12.0 ± 0.89 kg were used. Piglets were assigned to one of four dietary treatments (n = 10): cereal and soya bean meal base diet (control), base diet with 10% Spirulina (SP), SP diet supplemented with 0.005% Rovabio® Excel AP (SP + R) and SP diet supplemented with 0.01% lysozyme (SP + L). Animals were slaughtered after a 4-week experimental period. Growth performance was negatively affected by the incorporation of Spirulina in the diets, with an average decrease of 9.1% on final weight, in comparison with control animals. Total tract apparent digestibility (TTAD) of crude protein was higher (p < .05) in the control group than in other groups. In addition, lysozyme increased TTAD of crude fat and acid detergent fibre, relative to the SP and control groups, respectively. In addition, the incorporation of Spirulina, individually and supplemented with enzymes, did not impair meat quality traits. Surprisingly, no protective effect against lipid oxidation was observed with the inclusion of Spirulina in pork after 7 days of storage. This study indicates that growth performance of post-weaning piglets was impaired by the incorporation of 10% Spirulina in the diets, which is mediated by an increase in digesta viscosity and a lower protein digestibility, as a consequence of the resistance of microalga proteins to the action of endogenous peptidases. In addition, it also indicates that lysozyme, in contrast to Rovabio® Excel AP, is efficient in the degradation of Spirulina cell wall in piglet's intestine. However, the digestion of proteins liberated by Spirulina cell wall disruption is still a challenge.

A two-enzyme constituted mixture to improve the degradation of Arthrospira platensis microalga cell wall for monogastric diets.

The main goal of this study was to test a rational combination of pre-selected carbohydrate-active enzymes (CAZymes) and sulphatases, individually or in combination, in order to evaluate its capacity to disrupt Arthrospira platensis cell wall, allowing the release of its valuable nutritional bioactive compounds. By the end, a two-enzyme constituted mixture (Mix), composed by a lysozyme and a α-amylase, was incubated with A. platensis suspension. The microalga cell wall disruption was evaluated through the amount of reducing sugars released from the cell wall complemented with the oligosaccharide profile by HPLC. An increase of the amount of reducing sugars up to 2.42 g/L in microalgae treated with the Mix relative to no treatment (p < .05), as well as a 7-fold increase of oligosaccharides amount (p < .001), were obtained. With resort of fluorescence microscopy, a 36% reduction of fluorescence intensity (p < .001) was observed using Calcofluor White staining. In the supernatant, the Mix caused a 1.34-fold increase in protein content (p = .018) relative to the control. Similarly, n-6 polyunsaturated fatty acids (PUFA) (p = .007), in particular 18:2n-6 (p = .016), monounsaturated fatty acids (MUFA) (p = .049) and chlorophyll a (p = .025) contents were higher in the supernatant of microalgae treated with the enzyme mixture in relation to the control. Taken together, these results point towards the disclosure of a novel two-enzyme mixture able to partial degrade A. platensis cell wall, improving its nutrients bioavailability for monogastric diets with the cost-effective advantage use of microalgae in animal feed industry.

Amino acid profiles of muscle and liver tissues of Australian Merino, Damara and Dorper lambs under restricted feeding.

Seasonal weight loss (SWL) is a major constraint in extensive animal production systems in the tropics and Mediterranean. The objective of this study was to characterize the amino acid profile of muscle and hepatic tissues of Australian Merino, Damara and Dorper lambs under restricted feeding to evaluate the impact of SWL at the metabolic and physiological levels. SWL induced generalized muscle protein breakdown among restricted groups of all breeds, with varying intensity. Dorper breed mobilized less muscle amino acids when under these conditions, with the Damara having frequent significant differences, namely by having lower amino acid concentrations in the muscle of restricted lambs. Damara lambs showed greater ability to catabolize branched-chain amino acids in the muscle tissue, which indicates yet another mechanism that provides the Damara with the necessary tools to endure harsh conditions. Overall, the Damara breed mobilized more muscle amino acids than the other breeds, with a better capacity to catabolize branched-chain amino acids in the muscle, while maintaining muscle structural integrity.

Modulation of aquaporin gene expression by n-3 long-chain PUFA lipid structures in white and brown adipose tissue from hamsters.

EPA (20 : 5n-3) and DHA (22 : 6n-3) fatty acids have weight-reducing properties with physiological activity depending on their molecular structure - that is, as TAG or ethyl esters (EE). Aquaporins (AQP) are membrane protein channels recognised as important players in fat metabolism, but their differential expression in white adipose tissue (WAT) and brown adipose tissue (BAT), as well as their modulation by dietary n-3 long-chain PUFA (LCPUFA) such as EPA and DHA, has never been investigated. In this study, the transcriptional profiles of AQP3, AQP5, AQP7 and selected lipid markers of WAT (subcutaneous and visceral) and BAT (interscapular) from hamsters fed diets containing n-3 LCPUFA in different lipid structures such as fish oil (FO, rich in EPA and DHA in the TAG form) and FO-EE (rich in EPA and DHA in the EE form) were used and compared with linseed oil (LSO) as the reference group. A clear effect of fat depot was observed for AQP3 and leptin (LEP), with the lowest values of mRNA found in BAT relative to WAT. The opposite occurred for PPARα. AQP7 was affected by diet, with FO-fed hamsters having higher mRNA levels compared with LSO-fed hamsters. The relative gene expression of AQP5, adiponectin (ADIPO), GLUT4 and PPARγ was influenced by both fat tissue and diet. Taken together, our results revealed a differential expression profile of AQP and some markers of lipid metabolism in both WAT and BAT in response to feeding n-3 LCPUFA in two different structural formats: TAG v. EE.

Unsafe Drug Use and Arrhythmic Events in Brugada Patients with ICD: Results of a Long-Term Follow-Up.

PURPOSE: Brugada syndrome is a hereditary disease linked with an increased risk of sudden death that may require an implantable cardioverter-defibrillator (ICD) in order to halt the arrhythmic events. The aim of this study was to identify possible triggers for appropriate ICD therapies in patients with Brugada syndrome, focusing on their past and current therapeutic profiles. METHODS: Thirty patients with high-risk Brugada syndrome, with ICD implanted at the Coimbra Hospital and University Center, were enrolled. Patients were questioned about their Brugada syndrome history, previous cardiac events, comorbidities, present and past medications, and physical activity. Patients were followed up during 5.8 ± 5.3 years. The ICD was interrogated, and arrhythmic events and device therapies were recorded. The cohort who received appropriate ICD therapies was compared with the remaining patients to determine the potential link between clinical variables and potentially fatal arrhythmic events. RESULTS: More than half of the patients (53.3%) took at least one non-recommended drug, and 16.7% received appropriate ICD therapies, with a long-term rate of 4.0%/year. There was a tendency for more appropriate ICD therapies in patients who took unsafe drugs (85.7 versus 45.5%, p = 0.062), and the mean time between unsafe drug intake and appropriate ICD therapies was 3.8 ± 7.5 days. CONCLUSIONS: This study revealed that the medical community is still unaware of the pharmacological restrictions imposed by Brugada syndrome. Patients who took non-recommended drugs seem to have a higher risk of ventricular arrhythmic events.

Docosahexaenoic acid (DHA) at the sn-2 position of triacylglycerols increases DHA incorporation in brown, but not in white adipose tissue, of hamsters.

We hypothesised that the incorporation of docosahexaenoic acid (DHA) across adipose tissues will be higher when it is ingested as triacylglycerols (TAG) structured at the sn-2 position. Ten-week old male hamsters were allocated to 4 dietary treatments (n = 10): linseed oil (LSO-control group), fish oil (FO), fish oil ethyl esters (FO-EE) and structured DHA at the sn-2 position of TAG (DHA-SL) during 12 weeks. In opposition to the large variations found for fatty acid composition in retroperitoneal white adipose tissue (WAT), brown adipose tissue (BAT) was less responsive to diets. DHA was not found in subcutaneous and retroperitoneal WAT depots but it was successfully incorporated in BAT reaching the highest percentage in DHA-SL. The PCA on plasma hormones (insulin, leptin, adiponectin) and fatty acids discriminated BAT from WATs pointing towards an individual signature on fatty acid deposition, but did not allow for full discrimination of dietary treatments within each adipose tissue.

Betaine and arginine supplementation of low protein diets improves plasma lipids but does not affect hepatic fatty acid composition and related gene expression profiling in pigs.

BACKGROUND: The individual and combined effects of betaine and arginine supplemented to reduced protein diets were investigated on plasma metabolites, hepatic fatty acid composition and mRNA levels of lipid-sensitive factors in commercial pigs. Betaine has previously been shown to reduce carcass fat deposition and arginine improves meat quality of finishing pigs. Forty male crossbred pigs were randomly assigned to one of five diets (n = 8): 160 g kg-1 of crude protein (NPD), 130 g kg-1 of crude protein (RPD), RPD with 3.3 g kg-1 of betaine, RPD with 15 g kg-1 of arginine, and RPD with 3.3 g kg-1 of betaine and 15 g kg-1 of arginine. RESULTS: The restriction of dietary protein increased total lipids (P < 0.001), total cholesterol (P < 0.001), high-density lipoprotein-cholesterol (P < 0.001) and low-density lipoprotein cholesterol (P < 0.001). Betaine and arginine, individually or combined, reduced the majority of plasma lipids (P < 0.05) without affecting total fatty acids in the liver and the overall gene expression pattern. CONCLUSION: These findings suggest a positive effect of betaine and arginine, singly or combined, by reversing plasma lipids increase promoted by dietary protein restriction. © 2017 Society of Chemical Industry.

Who still remains at risk of arrhythmic death at time of implantable cardioverter-defibrillator generator replacement?

BACKGROUND: Implantable cardioverter-defibrillator (ICD) is associated with reduction in arrhythmic mortality. However, at the time of generator replacement (GR) some patients had not experienced therapies and had a different clinical profile. Therefore, the risk-benefit ratio of ICD may have changed. Our aim was to determine the proportion of patients with ICD implanted in primary prevention that maintain guideline-derived indications at the time of GR and assess predictors of therapies in the postreplacement period. We evaluate the long-term benefit of ICD after GR in nonischemic cardiomyopathy (NICM) versus ischemic cardiomyopathy (ICM). METHODS: We included 141 patients undergoing GR from 11/2009 to 7/2015. Patients were divided into: G1 - guideline congruent indication for ICD at the time of GR (left ventricular ejection fraction [LVEF] ≤ 35% or appropriate therapies) and G2 - guideline incongruent indication (patients without appropriate therapies and LVEF >35%). We also compared ICD benefit between ICM and NICM patients. RESULTS: Maintenance of guideline-driven indications for ICD (G1) was present in 68% of patients and 32% had recovery of LVEF and no ICD therapies at the time of GR (G2). After GR, G2 patients showed a lower rate of appropriate therapies (3% vs 33%, P < 0.01). LVEF ≤ 35% was the only independent predictor of appropriate therapies (OR 12.0, P < 0.01). In multivariate analysis, etiology of heart failure did not predict the arrhythmic risk. CONCLUSION: At the time of GR, a significant proportion of patients no longer met guideline indications for ICD and their need for therapies is reduced. The etiology of heart failure did not predict freedom from therapies.

Arginine supplementation modulates pig plasma lipids, but not hepatic fatty acids, depending on dietary protein level with or without leucine.

BACKGROUND: In the present study, the effect of arginine and leucine supplementation, and dietary protein level, were investigated in commercial crossbred pigs to clarify their individual or combined impact on plasma metabolites, hepatic fatty acid composition and mRNA levels of lipid sensitive factors. The experiment was conducted on fifty-four entire male pigs (Duroc × Pietrain × Large White × Landrace crossbred) from 59 to 92 kg of live weight. Each pig was randomly assigned to one of six experimental treatments (n = 9). The treatments followed a 2 × 3 factorial arrangement, providing two levels of arginine supplementation (0 vs. 1%) and three levels of basal diet (normal protein diet, NPD; reduced protein diet, RPD; reduced protein diet with 2% of leucine, RPDL). RESULTS: Significant interactions between arginine supplementation and protein level were observed across plasma lipids. While dietary arginine increased total lipids, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol and triacylglycerols in NPD, the inverse effect was observed in RPD. Overall, dietary treatments had a minor impact on hepatic fatty acid composition. RPD increased 18:1c9 fatty acid while the combination of leucine and RPD reduced 18:0 fatty acid. Arginine supplementation increased the gene expression of FABP1, which contributes for triacylglycerols synthesis without affecting hepatic fatty acids content. RPD, with or without leucine addition, upregulated the lipogenic gene CEBPA but downregulated the fat oxidation gene LPIN1. CONCLUSIONS: Arginine supplementation was responsible for a modulated effect on plasma lipids, which is dependent on dietary protein level. It consistently increased lipaemia in NPD, while reducing the correspondent metabolites in RPD. In contrast, arginine had no major impact, neither on hepatic fatty acids content nor on fatty acid composition. Likewise, leucine supplementation of RPD, regardless the presence of arginine, promoted no changes on total fatty acids in the liver. Ultimately, arginine, leucine and dietary protein reduction seem to be unrelated with fatty liver development.

Restriction of dietary protein does not promote hepatic lipogenesis in lean or fatty pigs.

The influence of genotype (lean v. fatty) and dietary protein level (normal v. reduced) on plasma metabolites, hepatic fatty acid composition and mRNA levels of lipid-sensitive factors is reported for the first time, using the pig as an experimental model. The experiment was conducted on forty entire male pigs (twenty lean pigs of Large White×Landrace×Pietrain cross-breed and twenty fatty pigs of Alentejana purebreed) from 60 to 93 kg of live weight. Each pig genotype was divided into two subgroups, which were fed the following diets: a normal protein diet (NPD) equilibrated for lysine (17·5 % crude protein and 0·7 % lysine) and a reduced protein diet (RPD) not equilibrated for lysine (13·1 % crude protein and 0·4 % lysine). The majority of plasma metabolites were affected by genotype, with lean pigs having higher contents of lipids, whereas fatty pigs presented higher insulin, leptin and urea levels. RPD increased plasma TAG, free fatty acids and VLDL-cholesterol compared with NPD. Hepatic total lipids were higher in fatty pigs than in the lean genotype. RPD affected hepatic fatty acid composition but had a slight influence on gene expression levels in the liver. Sterol regulatory element-binding factor 1 was down-regulated by RPD, and fatty acid desaturase 1 (FADS1) and fatty acid binding protein 4 (FABP4) were affected by the interaction between genotype and diet. In pigs fed RPD, FADS1 was up-regulated in the lean genotype, whereas FABP4 increased in the fatty genotype. Although there is a genotype-specific effect of dietary protein restriction on hepatic lipid metabolism, lipogenesis is not promoted in the liver of lean or fatty pigs.

Influence of betaine and arginine supplementation of reduced protein diets on fatty acid composition and gene expression in the muscle and subcutaneous adipose tissue of cross-bred pigs.

The isolated or combined effects of betaine and arginine supplementation of reduced protein diets (RPD) on fat content, fatty acid composition and mRNA levels of genes controlling lipid metabolism in pig m. longissimus lumborum and subcutaneous adipose tissue (SAT) were assessed. The experiment was performed on forty intact male pigs (Duroc×Large White×Landrace cross-breed) with initial and final live weights of 60 and 93 kg, respectively. Pigs were randomly assigned to one of the following five diets (n 8): 16·0 % of crude protein (control), 13·0 % of crude protein (RPD), RPD supplemented with 0·33 % of betaine, RPD supplemented with 1·5 % of arginine and RPD supplemented with 0·33 % of betaine and 1·5 % of arginine. Data confirmed that RPD increase intramuscular fat (IMF) content and total fat content in SAT. The increased total fat content in SAT was accompanied by higher GLUT type 4, lipoprotein lipase and stearoyl-CoA desaturase mRNA expression levels. In addition, the supplementation of RPD with betaine and/or arginine did not affect either IMF or total fat in SAT. However, dietary betaine supplementation slightly affected fatty acid composition in both muscle and SAT. This effect was associated with an increase of carnitine O-acetyltransferase mRNA levels in SAT but not in muscle, which suggests that betaine might be involved in the differential regulation of some key genes of lipid metabolism in pig muscle and SAT. Although the arginine-supplemented diet decreased the mRNA expression level of PPARG in muscle and SAT, it did not influence fat content or fatty acid composition in any of these pig tissues.

Two-dimensional speckle tracking cardiac mechanics and constrictive pericarditis: systematic review.

Transthoracic echocardiography has a pivotal role in the diagnosis of constrictive pericarditis (CP). In addition to the classic M-mode, two-dimensional and Doppler indices, newer methodologies designed to evaluate myocardial mechanics, such as two-dimensional speckle tracking echocardiography (2DSTE), provide additional diagnostic and clinical information in the context of CP. Research has demonstrated that cardiac mechanics can improve echocardiographic diagnostic accuracy of CP and aid in differentiating between constrictive and restrictive ventricular physiology. 2DSTE can also be used to assess the success of pericardiectomy and its impact on atrial and ventricular mechanics. In the course of this review, we describe cardiac mechanics in patients with CP and summarize the influence of pericardiectomy on atrial and ventricular mechanics assessed using 2DSTE.

Combined effects of dietary arginine, leucine and protein levels on fatty acid composition and gene expression in the muscle and subcutaneous adipose tissue of crossbred pigs.

The cumulative effects of dietary arginine, leucine and protein levels on fat content, fatty acid composition and mRNA levels of genes controlling lipid metabolism in pig longissimus lumborum muscle and subcutaneous adipose tissue (SAT) were investigated. The experiment was performed on fifty-four intact male pigs (Duroc × Pietrain × Large White × Landrace crossbred), with a live weight ranging from 59 to 92 kg. The pigs were randomly assigned to one of six experimental treatments (n 9). The treatments followed a 2 × 3 factorial arrangement, with two levels of arginine supplementation (0 v. 1 %) and three levels of a basal diet (normal protein diet, NPD; reduced protein diet, RPD; reduced protein diet to achieve 2 % of leucine, RPDL). The results showed that dietary arginine supplementation did not affect the intramuscular fat (IMF) content and back fat thickness, but increased the total fat in SAT. This effect was associated with an increase in fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD) mRNA levels in SAT, which suggests that arginine might be involved in the differential regulation of some key lipogenic genes in pig muscle and SAT. The increase in IMF content under the RPD, with or without leucine supplementation, was accompanied by increased FASN and SCD mRNA levels. Arginine supplementation did not influence the percentage of main fatty acids, while the RPD had a significant effect on fatty acid composition in both tissues. Leucine supplementation of RPD did not change IMF, total fat of SAT and back fat thickness, but increased 16 : 0 and 18 : 1cis-9 and decreased 18 : 2n-6 in muscle.

Long-term prognosis of idiopathic ventricular fibrillation: An eighteen-year experience from a tertiary center.

INTRODUCTION AND OBJECTIVES: Idiopathic ventricular fibrillation (IVF) is diagnosed in patients who survive sudden cardiac arrest (SCA), preferably with documented ventricular fibrillation (VF), without any identifiable structural or electrical abnormality. Current evidence provides limited guidance on the diagnosis and follow-up of these patients. Our aim was to assess the clinical outcomes of survivors of an aborted SCA attributed to IVF. METHODS: We retrospectively collected clinical data from all patients who survived SCA and implanted a cardiac defibrillator (ICD) between 2005 and 2023. RESULTS: A total of 38 patients, 36.8% female, with a mean age of 44±14 years old were included. Median follow-up time was 8.7 years (interquartile range (IQR) 4.7-14.7 years). All patients underwent a comprehensive diagnostic evaluation that excluded structural and coronary disease. During follow-up, underlying diagnoses were established in 34.2% of the whole cohort. Genetic testing, performed in 37.2%, revealed underlying diagnoses in 57.1% of those tested, compared to only 26.3% of patients who did not undergo genetic testing [p=0.035, OR=5.1 (95% confidence interval (CI) 1.2-21.5)]. Mortality was 10.5% (due to non-arrhythmic causes) and 36.8% patients received appropriate therapies with a median time to first ICD therapy of 39 [5.4-47.3] months. CONCLUSION(S): Etiological diagnosis and recurrence prediction in patients with IVF remains challenging, even with extensive diagnostic evaluation and long-term follow-up. In our study, genetic testing enhanced diagnostic yield. Consistent with previous findings, our cohort experienced a notable arrhythmic recurrence, with no cardiac deaths, underlining the pivotal role of ICD implantation in these patients.

Severe Periprocedural Complications After Ablation for Atrial Fibrillation: An International Collaborative Individual Patient Data Registry.

BACKGROUND: Catheter ablation for atrial fibrillation (AF) including pulmonary vein isolation and possibly further substrate ablation is the most common electrophysiological procedure. Severe complications are uncommon, but their detailed assessment in a large worldwide cohort is lacking. OBJECTIVES: The aim of this study was to determine the incidence of periprocedural severe complications and to provide a detailed characterization of the diagnostic evaluation and management of these complications in patients undergoing AF ablation. METHODS: Individual patient data were collected from 23 centers worldwide. Limited data were collected for all patients who underwent catheter ablation, and an expanded series of data points were collected for patients who experienced severe complications during periprocedural follow-up. Incidence, predictors, patient characteristics, management details, and overall outcomes of patients who experienced ablation-related complications were investigated. RESULTS: Data were collected from 23 participating centers at which 33,879 procedures were performed (median age 63 years, 30% women, 71% radiofrequency ablations). The incidence of severe complications (n = 271) was low (tamponade 6.8‰, stroke 0.97‰, cardiac arrest 0.41‰, esophageal fistula 0.21‰, and death 0.21‰). Age, female sex, a dilated left atrium, procedure duration, and the use of radiofrequency energy were independently associated with the composite endpoint of all severe complications. Among patients experiencing tamponade, 13% required cardiac surgery. Ninety-three percent of patients with complications were discharged directly home after a median length of stay of 5 days (Q1-Q3: 3-7 days). CONCLUSIONS: This large worldwide collaborative study highlighted that tamponade, stroke, cardiac arrest, esophageal fistula, and death are rare after AF ablation. Older age, female sex, procedure duration, a dilated left atrium, and the use of radiofrequency energy were associated with severe complications in this multinational cohort. One in 8 patients with tamponade required cardiac surgery.

Differential effects of reduced protein diets on fatty acid composition and gene expression in muscle and subcutaneous adipose tissue of Alentejana purebred and Large White × Landrace × Pietrain crossbred pigs.

The present study assessed the effect of pig genotype (fatty v. lean) and dietary protein and lysine (Lys) levels (normal v. reduced) on intramuscular fat (IMF) content, subcutaneous adipose tissue (SAT) deposition, fatty acid composition and mRNA levels of genes controlling lipid metabolism. The experiment was conducted on sixty intact male pigs (thirty Alentejana purebred and thirty Large White × Landrace × Pietrain crossbred), from 60 to 93 kg of live weight. Animals were divided into three groups fed with the following diets: control diet equilibrated for Lys (17·5 % crude protein (CP) and 0·7 % Lys), reduced protein diet (RPD) equilibrated for Lys (13·2 % CP and 0·6 % Lys) and RPD not equilibrated for Lys (13·1 % CP and 0·4 % Lys). It was shown that the RPD increased fat deposition in the longissimus lumborum muscle in the lean but not in the fatty pig genotype. It is strongly suggested that the effect of RPD on the longissimus lumborum muscle of crossbred pigs is mediated via Lys restriction. The increase in IMF content under the RPD was accompanied by increased stearoyl-CoA desaturase (SCD) and PPARG mRNA levels. RPD did not alter backfat thickness, but increased the total fatty acid content in both lean and fatty pig genotype. The higher amount of SAT in fatty pigs, when compared with the lean ones, was associated with the higher expression levels of ACACA, CEBPA, FASN and SCD genes. Taken together, the data indicate that the mechanisms regulating fat deposition in pigs are genotype and tissue specific, and are associated with the expression regulation of the key lipogenic genes.

Differences in lipid deposition and adipose membrane biophysical properties from lean and obese pigs under dietary protein restriction.

Obesity consists in fat accumulation leading to increase in adipose cells number and size. Adipocyte membrane biophysical properties are critical to maintain cellular viability in metabolically healthy obesity. This study investigated the effect of the genetic background and dietary protein restriction on fat tissue lipid composition, adipocyte membrane fluidity and water permeability using the pig as experimental model. Twenty-four male pigs from distinct genotypes, lean and obese, were fed on normal and reduced protein diets within a 2 × 2 factorial arrangement (two genotypes and two diets). Backfat thickness was twofold higher in obese than in lean pigs but unrelated to dietary protein level. In contrast, total fatty acids in the subcutaneous adipose tissue were dependent on both breed and diet, with increased lipid content promoted by the fatty genotype and by the restriction of dietary protein. Adipose membranes isolated from obese pig's subcutaneous fat tissue showed higher permeability to water, in line with an increased fluidity. Moreover, the reduced content of dietary protein influenced positively the fluidity of adipose membranes. Neither genotype nor diet affected total cholesterol concentration in the adipose membranes. Membrane-saturated fatty acids' content was influenced by genotype, while membrane-polyunsaturated fatty acids, particularly from the n-6 family, was influenced by diet. The ratio of oleic (18:1c9)/linoleic (18:2n-6) acids was positively correlated with membrane fluidity. All together, these findings reinforce the genetic background as a determinant player on adipose membrane biophysical properties and point to the dietary protein level as an important factor for subcutaneous lipid deposition as well as for regulation of membrane function, factors that may have impact on human obesity and metabolic syndrome.