Real-world assessment of multipolar and point-by-point mapping for premature ventricular contraction ablation.

AIMS: We aimed to assess the acute and midterm efficacy of premature ventricular contraction (PVC) ablation guided by multielectrode and point-by-point (PbP) mapping. METHODS AND RESULTS: This is a retrospective, international multicentre study of consecutive patients referred for PVC ablation in 10 hospital centres from January 2017 to December 2021. Based on the mapping approach, two cohorts were identified: the 'Multipolar group', where a dedicated high-density mapping catheter was employed, and the 'PbP group', where mapping was performed with the ablation catheter. Procedural endpoints, safety, and acute (procedural) and midterm efficacies were assessed. Of the 698 patients included in this study, 592 received activation mapping [46% males, median age of 55 (41-65) years]-248 patients in the Multipolar group and 344 patients in the PbP group. A higher number of activation points [432 (217-843) vs. 95 (42-185), P < 0.001], reduced mapping time (40 ± 38 vs. 61 ± 50 min, P < 0.001), and shorter procedure time (124 ± 60 vs. 143 ± 63 min, P < 0.001) were reported in the Multipolar group. Both groups had high acute success rates (84.7% with Multipolar mapping vs. 81.3% with PbP mapping, P = 0.63), as well as midterm efficacy (83.4% vs. 77.4%, P = 0.08), with no significant differences in the risk of adverse events (6.0% vs. 3.5%, P = 0.24). However, for left-sided PVC ablation specifically, there was a higher midterm efficacy in the Multipolar group (80.7% vs. 69.5%, P = 0.04), with multipolar mapping being an independent predictor of success [adjusted OR = 2.231 (95% CI, 1.476-5.108), P = 0.02]. CONCLUSION: The acute and midterm efficacies of PVC ablation are high with both multipolar and PbP mapping, although the former allows for quicker procedures and may potentially improve the outcomes of left-sided PVC ablation.

Effect of cattle and horse feces storage methods on Nematode egg viability and sensitivity for egg hatch test.

The aim of the present study was to validate methods of stool sample conservation for the egg hatch test (EHT). This study involved the use of a bovine naturally infected predominantly by Cooperia spp. and one equine naturally infected predominantly by cyathostomins characterized as susceptible to benzimidazoles in the EHT. Fecal samples were submitted to three treatments: aerobic methods (anaerobic storage in plastic bottles, anaerobic storage in vacuum-sealed bags or aerobic storage in plastic bags), under two temperature conditions (room temperature and refrigeration) analyzed at four different assessment times (48, 72, 96 and 120 h). As the standard test, an assay was also performed within 3 h. The tests were performed in triplicate for each drug concentration and with three experimental repetitions at one-week intervals. Two criteria were used for the storage methods: hatchability in the negative control group and sensitivity of the eggs to thiabendazole, comparing the EC50 and 95% confidence interval for each treatment to those of the standard test and the other repetitions. Bovine samples can be stored for up to 96 h and refrigerated vacuum storage can be used, ensuring hatchability of the negative control and sensitivity of the eggs to thiabendazole. For equine samples, no forms of storage were indicated due to the variation among the repetitions and the reduction in the sensitivity of the eggs to thiabendazole, which could result in a false positive detection of resistance.

Biomarkers of gastrointestinal nematodes in beef cattle raised in a tropical area.

Biomarkers are specific molecular, histological, or physiological characteristics of normal or pathogenic biological processes and are promising in the diagnosis of gastrointestinal nematodes (GINs). Although some biomarkers have been validated for infection by Ostertagia sp. in cattle raised in temperate regions, there is a lack of information for tropical regions. The aim of this project was to assess potential biomarkers and validate the most promising. In the first study, 36 bovines (Nelore breed) naturally infected by GINs were distributed into two groups: infected (not treated with anthelmintic) and treated (treated with fenbendazole on days 0, 7, 14, 21, 28, 42, and 56). The variables of interest were live weight, fecal egg count, hemogram, serum biochemical markers, phosphorus, gastrin, and pepsinogen. In the second step, pepsinogen was assessed in cattle of the Nelore breed distributed among three groups: infected (not treated with anthelmintic), MOX (treated with moxidectin), and IVM + BZD (treated with ivermectin + albendazole). In the first study, no difference between groups was found for weight, albumin, hematocrit (corpuscular volume [CV]), erythrocytes, or hemoglobin. Negative correlations were found between pepsinogen and both CV and albumin, and albumin was negatively correlated with the percentage of Haemonchus sp. in the fecal culture. Among the biomarkers, only pepsinogen differentiated treated and infected (beginning with the 28th day of the study). In the second study, a reduction in pepsinogen was found after anthelmintic treatment. Therefore, pepsinogen is a promising biomarker of worms in cattle naturally infected by the genera Haemonchus and Cooperia in tropical areas.

Mid-term outcomes after catheter ablation in patients with congenital heart disease.

INTRODUCTION: Cardiac arrhythmias are a major concern in patients with CHD. The purpose of this study was to evaluate the long-term outcomes in patients with CHD submitted to catheter ablation. MATERIALS AND METHODS: Observational retrospective study of patients with CHD referred for catheter ablation from January 2016 to December 2021 in a tertiary referral centre. Acute procedural endpoints and long-term outcomes were assessed. RESULTS: A total of 44 ablation procedures were performed in 36 CHD patients (55% male, mean age 43 ±3 years). Fifty-four arrhythmias were ablated: 23 cavotricuspid isthmus atrial flutters, 10 atrial re-entrant tachycardias, eight focal atrial tachycardias, eight atrial fibrillations, three atrioventricular re-entrant tachycardias, and two ventricular tachycardias. During a median follow-up time of 37 months (interquartile range 12-51), freedom from arrhythmia recurrence was achieved in 93%, with 1.2 procedures per patient (18% with anti-arrhythmic drugs). There were no adverse events related to catheter ablation. No predictors of recurrence were identified. CONCLUSION: In patients with CHD, catheter ablation presents a high mid-term efficacy while maintaining a safe profile.

Effects of pasture management and supplementation on the productive performance of recently lambed ewes.

The hypothesis was tested that the performance of lactating ewes is affected by the supplementation level and pasture management. Two supplementation levels (0.5 and 1.0% of body weight, BW) and two pasture managements (mowed and non-mowed) were tested. Forty adult ewes (2 years old) with an average weight at lambing of 62.97 ± 7.0 kg (day 0) and an average the body condition score of 2.5 points (day 0) were evaluated. Verminosis was monitored with periodic deworming. The number of eggs per gram of feces (EPG) of ewes at lambing was used as a covariate for performance assessments. Ewes lost an average of 7.5 kg over the 90 days post-partum (12% BW). The weaning rate was 53%. The body condition of the ewes was influenced by the post-partum period. The ewes mobilized their body reserves in the first 30 days of lactation. Mowing management negatively affected the nutritive value of the forage. Supplementation with 0.5% BW was sufficient for nutritional management post-partum. Pasture management (mowed vs. not mowed) cannot prevent post-partum weight loss. Supplementation levels and pasture management altered the morphological and chemical components of the pasture.

Ostial vs. wide area circumferential ablation guided by the Ablation Index in paroxysmal atrial fibrillation.

AIMS: Pulmonary vein isolation (PVI) guided by the Ablation Index (AI) has shown high acute and mid-term efficacy in the treatment of paroxysmal atrial fibrillation (AF). Previous data before the AI-era had suggested that wide-area circumferential ablation (WACA) was preferable to ostial ablation. However, with the use of AI, we hypothesize that ostial circumferential ablation is non-inferior to WACA and can improve outcomes in paroxysmal AF. METHODS AND RESULTS: Prospective, multicentre, non-randomized, non-inferiority study of consecutive patients were referred for paroxysmal AF ablation from January 2020 to September 2021. All procedures were performed using the AI software, and patients were separated into two different groups: WACA vs. ostial circumferential ablation. Acute reconnection, procedural data, and 1-year arrhythmia recurrence were assessed. During the enrolment period, 162 patients (64% males, mean age of 60 ± 11 years) fulfilled the study inclusion criteria-81 patients [304 pulmonary vein (PV)] in the WACA group and 81 patients (301 PV) in the ostial group. Acute PV reconnection was identified in 7.9% [95% confidence interval (CI), 4.9-11.1%] of PVs in the WACA group compared with 3.3% (95% CI, 1.8-6.1%) of PVs in the ostial group [P < 0.001 for non-inferiority; adjusted odds ratio 0.51 (95% CI, 0.23-0.83), P = 0.05]. Patients in the WACA group had longer ablation (35 vs. 29 min, P = 0.001) and procedure (121 vs. 102 min, P < 0.001) times. No significant difference in arrhythmia recurrence was seen at 1-year of follow-up [11.1% in WACA vs. 9.9% in ostial, hazard ratio 1.13 (95% CI, 0.44-1.94), P = 0.80 for superiority]. CONCLUSION: In paroxysmal AF patients treated with tailored AI-guided PVI, ostial circumferential ablation is not inferior to WACA with regard to acute PV reconnection, while allowing quicker procedures with less ablation time.

Reduced numbers of regulatory T cells in chronic heart failure seems not to be restored by cardiac resynchronization therapy.

BACKGROUND: T cells have been implicated in the development and progression of inflammatory processes in chronic heart failure (CHF). Cardiac resynchronization therapy (CRT) has beneficial effects on symptoms and cardiac remodeling in CHF. However, its impact on the inflammatory immune response remains controversial. We aimed to study the impact of CRT on T cells in heart failure (HF) patients. METHODS: Thirty-nine HF patients were evaluated before CRT (T0) and six months later (T6). Quantification of T cells, their subsets, and their functional characterization, after in vitro stimulation, were evaluated by flow cytometry. RESULTS: T regulatory (Treg) cells were decreased in CHF patients (healthy group (HG): 1.08 ± 0.50 versus (heart failure patients (HFP)-T0: 0.69 ± 0.40, P = 0.022) and remaining diminished after CRT (HFP-T6: 0.61 ± 0.29, P = 0.003). Responders (R) to CRT presented a higher frequency of T cytotoxic (Tc) cells producing IL-2 at T0 compared with non-responders (NR) (R: 36.52 ± 12.55 versus NR: 24.71 ± 11.66, P = 0.006). After CRT, HF patients presented a higher percentage of Tc cells expressing TNF-α and IFN-γ (HG: 44.50 ± 16.62 versus R: 61.47 ± 20.54, P = 0.014; and HG: 40.62 ± 15.36 versus R: 52.39 ± 18.66, P = 0.049, respectively). CONCLUSION: The dynamic of different functional T cell subpopulations is significantly altered in CHF, which results in an exacerbated pro-inflammatory response. Even after CRT, it seems that the inflammatory condition underlying CHF continues to evolve with the progression of the disease. This could be due, at least in part, to the inability to restore Treg cells levels. TRIAL REGISTRATION: Observational and prospective study with no trial registration.

"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.

Role of monocytes and dendritic cells in cardiac reverse remodelling after cardiac resynchronization therapy.

BACKGROUND AND AIMS: Monocytes and dendritic cells (DC) are both key inflammatory cells, with recognized effects on cardiac repair. However, there are distinct subsets of monocytes with potential for beneficial or detrimental effects on heart failure (HF) pathogenesis. The connection between reverse cardiac remodelling, the potential anti-inflammatory effect of cardiac resynchronization therapy (CRT) and monocytes and DC homeostasis in HF is far from being understood. We hypothesized that monocytes and DC play an important role in cardiac reverse remodelling and CRT response. Therefore, we aimed to assess the potential role of baseline peripheral levels of blood monocytes and DC subsets and their phenotypic and functional activity for CRT response, in HF patients. As a secondary objective, we aimed to evaluate the impact of CRT on peripheral blood monocytes and DC subsets, by comparing baseline and post CRT circulating levels and phenotypic and functional activity. METHODS: Forty-one patients with advanced HF scheduled for CRT were included in this study. The quantification and phenotypic determination of classical (cMo), intermediate (iMo) and non-classical monocytes (ncMo), as well as of myeloid (mDC) and plasmacytoid DC (pDC) were performed by flow cytometry in a FACSCanto™II (BD) flow cytometer. The functional characterization of total monocytes and mDC was performed by flow cytometry in a FACSCalibur flow cytometer, after in vitro stimulation with lipopolysaccharide from Escherichia coli plus interferon (IFN)-γ, in the presence of Brefeldina A. Comparisons between the control and the patient group, and between responders and non-responders to CRT were performed. RESULTS: Compared to the control group, HF population presented a significantly lower frequency of pDC at baseline and a higher proportion of monocytes and mDC producing IL-6 and IL-1ß, both before and 6-months after CRT (T6). There was a remarkable decrease of cMo and an increase of iMo after CRT, only in responders. The responder group also presented higher ncMo values at T6 compared to the non-responder group. Both responders and non-responders presented a decrease in the expression of CD86 in all monocyte and DC populations after CRT. Moreover, in non-responders, the increased frequency of IL-6-producing DC persisted after CRT. CONCLUSION: Our study provides new knowledge about the possible contribution of pDC and monocytes subsets to cardiac reverse remodelling and response to CRT. Additionally, CRT is associated with a reduction on CD86 expression by monocytes and DC subsets and in their potential to produce pro-inflammatory cytokines, contributing, at least in part, for the well described anti-inflammatory effects of CRT in HF patients.

VDD pacemaker: An effective and reliable physiological pacing modality in elderly patients.

BACKGROUND: In elderly patients, single chamber pacing may be considered. For sinus rhythm patients, VDD pacemaker (PM), by preserving atrial sensing, is a more physiological mode than VVI devices. This study aims to evaluate the long-term performance of VDD PM in elderly patients with atrioventricular block (AVB). METHODS: We conducted a retrospective, observational study of 200 elderly patients (≥75 years) with AVB and normal sinus rhythm who consecutively implanted VDD PM between 2016 and 2018. Baseline clinical characteristics were analyzed, complications related to pacemaker implantation were assessed and a 3-years follow-up (FUP) was made. RESULTS: Mean age was 84 ± 5 years. After 3-years FUP, 90.5% (n = 181) of the patients preserved their original VDD mode. Only 19 patients (9.5%) switched to VVIR mode, 5.5% (n = 11) due to P-wave undersensing and 4% (n = 8) due to permanent AF. Those patients had a less amplitude of sensed P wave at baseline [median value of 1.30 (IQR 0.99-2.0) versus 0.97 (IQR 0.38-1.68), p = 0.04]. One third of the patients died during the FUP, 89% (n = 58) from non-cardiovascular causes. All-cause, CV, and non-CV mortality did not relate with atrial sensing loss during FUP (p = 0.58, p = 0.38 and p = 0.80, respectively). However, atrial sensing loss during FUP was associated with de novo atrial fibrillation (12.7% vs. 31.6%, p = 0.038). CONCLUSION: VDD pacing is a reliable pacing modality in elderly patients even in long-term. The majority of VDD-paced elderly patients maintained their original VDD mode program, with good atrial sensing.

Synergism of macrocyclic lactones against Haemonchus contortus.

A possible synergistic effect of macrocyclic lactones' (MLs) combination has been previously described against resistant gastrointestinal nematodes of cattle. In addition to synergism, drug-drug interactions between MLs can also result in additive or antagonistic effect, considering the different MLs pharmacokinetics, pharmacodynamics, and interactions with molecular mechanisms of resistance. Therefore, the aim of the current work was evaluated the effect of different MLs combinations against Haemonchus contortus. Infecting larvae of two isolates (one susceptible and one resistant to ivermectin) were used in the larval migration inhibition test. After estimating the half maximal effective concentration of abamectin (ABA), eprinomectin, (EPR), ivermectin (IVM), and moxidectin (MOX) for both isolates, combinations were delineated by a simplex-centroid mixture experiment, and the mixture regression analysis was applied to the special cubic model. A synergistic effect was found for the EPR + MOX against the susceptible isolate as well as the EPR + MOX, IVM + MOX, and ABA + EPR + IVM against the resistant isolate. An antagonistic effect of ABA + IVM + MOX was found against the susceptible isolate. For the susceptible isolate, a higher inhibition was found with greater proportions of EPR and lower proportions of the other drugs compared to the reference mixture. For the resistant isolate, inhibition greater than that of the reference mixture was found with higher proportions of IVM as well as lower proportions of the other drugs. The synergistic and antagonistic effects were dependent on the following: (a) parasite drug resistance profile, (b) the composition of the combination, and (c) the proportions used, with EPR and IVM exerting a greater impact on these effects.

Assessment of the need of a waiting period after pulmonary vein isolation with the ablation index software.

PURPOSE: Since the widespread availability of contact-force sensing catheters, the need for a waiting period after pulmonary vein isolation (PVI) has not been reassessed. We aim to evaluate whether a waiting period is still necessary after PVI guided by the ablation Index (AI). METHODS: Prospective, multicenter, randomized study of consecutive patients referred for paroxysmal atrial fibrillation (AF) ablation from May 2019 to February 2020. Patients were randomized in a 1:1 ratio to PVI with versus without a waiting period of 20 min. Acute pulmonary vein (PV) reconnection after adenosine challenge was the primary endpoint. A per-protocol analysis was designed to determine whether a strategy of dismissing the waiting period after PVI was noninferior to waiting for 20 min for identifying acute PV reconnection. PVI was guided by tailored AI values and an interlesion distance ≤6 mm. RESULTS: During the enrollment period, 167 patients (56% males, mean age of 57 ± 14 years) fulfilled the study inclusion criteria - 84 patients (308 PV) in the waiting period group (Group A) and 83 patients (314 PV) in the group without a waiting period (Group B). Acute PV reconnection was identified in 3.8% (95% confidence interval [CI], 1.7%-5.9%) of PVs in the study group B compared to 2.9% (95% CI, 1.0%-4.8%) of PVs in the Group A (p = .002 for non-inferiority). At 1-year follow-up, there was no significant difference in arrhythmia recurrence between groups (9.5% in Group A vs. 9.6% in Group B, hazard ratio: 1.03 [95% CI, 0.39-2.73], p = .98). CONCLUSION: In paroxysmal AF patients submitted to ablation, a tailored PVI guided by the AI rendered a 20-min waiting period unnecessary.

Defining electrocardiographic criteria to differentiate non-type 1 Brugada ECG variants from normal incomplete RBBB patterns in the young SCD-SOS cohort.

INTRODUCTION: We assessed the prevalence of non-type 1 Brugada pattern (T1BrP) in children and young adults from the Sudden Cardiac Death-Screening Of risk factorS cohort and the diagnostic yield of nonexpert manual and automatic algorithm electrocardiogram (ECG) measurements. METHODS: Cross-sectional study. We reviewed 14 662 ECGs and identified 2226 with a rSr'-pattern in V1-V2. Among these, 115 were classified by experts in hereditary arrhythmic-syndromes as having or not non-T1BrP, and were compared with measurements of 5 ECG-derived parameters based on a triangle formed by r' -wave (d(A), d(B), d(B)/h, ß-angle) and ST-ascent, assessed both automatically and manually by nonexperts. We estimated intra- and interobserver concordance for each criterion, calculated diagnostic accuracy and defined the most appropriate cut-off values. RESULTS: A rSr'-pattern in V1-V2 was associated with higher PQ interval and QRS duration, male gender, and lower body mass index (BMI). The manual measurements of non-T1BrP criteria were moderately reproducible with high intraobserver and moderate interobserver concordance coefficients (ICC: 0.72-0.98, and 0.63-0.76). Criteria with higher discriminatory capacity were: distance d(B) (0.72; 95% confidence interval [CI]: 0.65-0.80) and ST-ascent (0.87; 95% CI: 0.82-0.92), which was superior to the 4 r'-wave criteria together (area under curve [AUC: 0.74]). We suggest new cut-offs with improved combination of sensitivity and specificity: d(B) ≥ 1.4 mm and ST-ascent ≥ 0.7 mm (sensitivity: 1%-82%; specificity: 71%-84%), that can be automatically measured to allow classification in four morphologies with increasing non-T1BrP probability. CONCLUSION: rSr'-pattern in precordial leads V1-V2 is a frequent finding and the detection of non-T1BrP by using the aforementioned five measurements is reproducible and accurate. In this study, we describe new cut-off values that may help untrained clinicians to identify young individuals who may require further work-up for a potential Brugada Syndrome diagnosis.

EHD1 Modulates Cx43 Gap Junction Remodeling Associated With Cardiac Diseases.

RATIONALE: Efficient communication between heart cells is vital to ensure the anisotropic propagation of electrical impulses, a function mainly accomplished by gap junctions (GJ) composed of Cx43 (connexin 43). Although the molecular mechanisms remain unclear, altered distribution and function of gap junctions have been associated with acute myocardial infarction and heart failure. OBJECTIVE: A recent proteomic study from our laboratory identified EHD1 (Eps15 [endocytic adaptor epidermal growth factor receptor substrate 15] homology domain-containing protein 1) as a novel interactor of Cx43 in the heart. METHODS AND RESULTS: In the present work, we demonstrate that knockdown of EHD1 impaired the internalization of Cx43, preserving gap junction-intercellular coupling in cardiomyocytes. Interaction of Cx43 with EHD1 was mediated by Eps15 and promoted by phosphorylation and ubiquitination of Cx43. Overexpression of wild-type EHD1 accelerated internalization of Cx43 and exacerbated ischemia-induced lateralization of Cx43 in isolated adult cardiomyocytes. In addition, we show that EHDs associate with Cx43 in human and murine failing hearts. CONCLUSIONS: Overall, we identified EHDs as novel regulators of endocytic trafficking of Cx43, participating in the pathological remodeling of gap junctions, paving the way to innovative therapeutic strategies aiming at preserving intercellular communication in the heart.

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.

Cardiac microcalcification burden: Global assessment in high cardiovascular risk subjects with Na[18F]F PET-CT.

BACKGROUND: Fluorine-18 sodium fluoride (Na[18F]F) atherosclerotic plaque uptake in positron emission tomography with computed tomography (PET-CT) identifies active microcalcification. We aim to evaluate global cardiac microcalcification activity with Na[18F]F, as a measure of unstable microcalcification burden, in high cardiovascular (CV) risk patients. METHODS AND RESULTS: Thirty-four high CV risk individuals without previous CV events were scanned with Na[18F]F PET-CT. Cardiac Na[18F]F uptake was assessed through the global molecular calcium score (GMCS), which was calculated by summing the product of the mean standardized uptake value times the area of the cardiac regions of interest times the slice thickness for all cardiac transaxial slices, divided by the total number of slices. Mean age is 63.5 ± 7.8 years and 62% male. Median GMCS is 320.9 (240.8-402.8). Individuals with more than five CV risk factors (50%) have increased GMCS [356.7 (321.0-409.6) vs. 261.1 (225.6-342.1), P = 0.01], which is positively correlated with predicted fatal CV risk by SCORE (rs = 0.32, P = 0.04). There is a positive correlation between GMCS and weight (rs = 0.61), body mass index (rs = 0.66), abdominal perimeter (rs = 0.74), thoracic fat volume (rs = 0.47), and epicardial adipose tissue (rs = 0.41), all with P ≤ 0.01. There is no correlation between GMCS and coronary calcium score nor coronary artery wall Na[18F]F uptake. CONCLUSIONS: In a high CV risk group, the global cardiac microcalcification burden is related to CV risk factors, metabolic syndrome variables and cardiac fat. Cardiac GMCS is a promising risk stratification tool, combining a straightforward and objective methodology with a comprehensive analysis of both coronary and valvular microcalcification.

A 45-year-old man with sudden cardiac death, cutaneous abnormalities and a rare desmoplakin mutation: a case report and literature review.

BACKGROUND: Arrhythmogenic cardiomyopathy (AC) is a rare, heritable myocardial disorder that is a leading cause of ventricular arrhythmia and sudden cardiac death (SCD) in young people. Desmoplakin (DSP) mutations account for 3-20% of AC cases. However, the number of patients with DSP mutations is extremely small in all published reports and genotype-phenotype correlations are scant and mostly non-gene-specific. CASE PRESENTATION: A 45-year-old man was admitted after an out-of-hospital cardiac arrest, with documented ventricular fibrillation. He had no previous history of heart disease or family history of SCD or cardiomyopathy. The cardiac magnetic resonance showed a mildly dilated left ventricle with an ejection fraction of 30% and a non-dilated right ventricle with mildly depressed systolic function, and extensive subepicardial late gadolinium enhancement. Genetic screening identified a heterozygote nonsense mutation in DSP (NM_004415.2: c.478 C > T; p.Arg160Ter). Cascade genetic screening of the relatives revealed a high prevalence of the genotype and cutaneous phenotype, but a very low penetrance of the cardiac phenotype. CONCLUSIONS: We report a case of SCD and an autosomal dominant mutation in DSP that causes arrhythmogenic dilated cardiomyopathy/AC. Like the recessive mutation in DSP known to cause Carvajal syndrome, Arg160Ter may be associated with cutaneous abnormalities.

High-risk features and predictors of unexplained syncope in the young SCD-SOS cohort.

INTRODUCTION: The Sudden Cardiac Death-Screening of Risk FactOrS survey included a 12-lead electrocardiogram (ECG) plus a digital-based questionnaire and aimed to screen for warning signs of diseases that may course with sudden cardiac death in children and young adults. We aimed to estimate the prevalence of unexplained syncope (US) and characterize its high-risk features and predictors in this cohort. METHODS AND RESULTS: We determined the most probable etiology of transient loss of consciousness (TLOC) episodes based on clinical criteria. US was an exclusion diagnosis and we analyzed its potential clinical and ECG predictors. Among 11 878 individuals, with a mean age of 21 ± 6 (range 6-40) years old, the cumulative incidence of TLOC was 26.5%, 76.2% corresponding to females. Reflex syncope was present in 66.4%, orthostatic hypotension in 8.2%, and 14.8% of the individuals had US. Unexplained syncope was independently associated with age < 18 years old (odds ratio [OR] 1.695; 95% confidence interval [CI] 1.26-2.29, p = .001), male gender (OR 1.642; 95% CI 1.22-2.22, p = .001), participation in competitive sports (OR 1.644; 95% CI 1.01-2.66, p = .043), syncope during exertion and/or palpitations preceding syncope (OR 2.556; 95% CI 1.92-3.40, p < .001), syncope after exertion (OR 2.662; 95% CI 1.73-4.10, p < .001), fever context (OR 9.606; 95% CI 4.13-22.34, p < .001), isolated previous syncopal episode (OR 2.780; 95% CI 0.2.06-3.75, p < .001), and history of palpitations requiring medical care (OR 1.945; 95% CI 1.14-3.31, p = .014). We found no ECG predictors of US in this population. CONCLUSIONS: The cumulative incidence of TLOC in children and young adults is high and remains unexplained in an important proportion of individuals. We identified eight clinical characteristics that may be useful for the risk stratification of individuals evaluated in a nonacute setting.

The efficacy and safety of direct oral anticoagulants plus aspirin in symptomatic lower extremity peripheral arterial disease: a systematic review and meta-analysis of randomized controlled trials.

Patients with lower extremity peripheral artery disease (PAD) are at increased risk of major adverse limb events (MALE). The efficacy and safety of direct oral anticoagulants (DOACs) in this context is evolving. To assess the efficacy and safety of DOAC combined with aspirin compared to the use of antiplatelet agents in patients with symptomatic lower extremity (LE) PAD. We systematically searched PubMed, Embase and Cochrane databases, in September 2020, for randomized controlled trials (RCTs) that were designed to investigate the effect of DOACs in the treatment of PAD. A random-effects meta-analysis was performed targeting ischemic and bleeding events. Three randomized clinical trials were included, providing a total of 9533 patients, and 744 pooled MALE events (316 in DOAC plus aspirin and 428 in control). Only data on rivaroxaban and edoxaban were available. The use of DOAC plus aspirin in PAD patients significantly decreased the rate of MALE (pooled OR 0.70 [0.61-0.83], P < 0.001; I2 = 0%). In terms of safety, there was a significantly higher rate of major bleeding events (pooled OR 1.46 [1.16-1.84], P = 0.001; I2 = 52%). In rivaroxaban-RCTs, the addition of low-dose rivaroxaban to aspirin was still associated with a lower MALE compared to aspirin alone (pooled OR 0.68 [0.53-0.88], P = 0.003; I2 = 28%), but also conferred higher major bleeding rate (pooled OR 1.48 [1.18-1.86], P < 0.001; I2 = 0%). In conclusion, our pooled data suggests that for patients with symptomatic LE-PAD, the use of DOAC combined with aspirin reduced the risk of major ischemic limb events at the expense of an increased risk of major bleeding.

Left atrial functional assessment and mortality in patients with severe aortic stenosis with sinus rhythm.

BACKGROUND: Aortic valve stenosis (AS) is the most common primary valvular heart disease leading to surgical or percutaneous aortic valve replacement (AVR) in Europe and its prevalence keeps growing. While other risk factors in severe AS are well documented, little is known about the prognostic value of left atrial (LA) function in AS. Our aim is to clarify the relationship between LA function measured at severe AS diagnosis (evaluated by means of volumetric assessment) and all-cause mortality during follow-up. METHODS: We retrospectively evaluated patients diagnosed with severe AS for the first time at our echocardiography laboratory. We evaluated LA reservoir, conduit and pump function by measuring LA volumes at different timings of cardiac cycle. Treatment strategy was decided according to heart team consensus and patient decision. We divided patients into groups according to terciles of LA reservoir, conduit and pump function. Primary outcome was defined by the occurrence of all-cause mortality during follow-up. RESULTS: A total of 408 patients were included in the analysis, with a median follow-up time of 45 months (interquartile range 54 months). 57.9% of patients underwent AVR and 44.9% of patients registered the primary outcome during follow-up. Left atrial emptying fraction (LAEF) was the best LA functional parameter and the best overall parameter in discriminating primary outcome (AUC 0.845, 95%CI 0.81-0.88, P < 0.001). After adjustment for clinical, demographic and echocardiographic variables, cumulative survival of patients with LAEF < 37% and LAEF 37 to 53% relative to patients with LAEF ≥54% remained significantly lower (HR 13.91, 95%CI 6.20-31.19, P < 0.001 and HR 3.40, 95%CI 1.57-7.37, P = 0.002, respectively). After adjustment for AVR, excess risk of LAEF < 37% and LAEF 37 to 53% relative to LAEF ≥54% remained significant (HR 11.71, 95%CI 5.20-26.40, P < 0.001 and HR 3.59, 95%CI 1.65-7.78, P = 0.001, respectively). CONCLUSIONS: In patients with a first diagnosis of severe AS, LA function, evaluated by means of volumetric assessment, is an independent predictor of all-cause mortality and a more potent predictor of death compared to classical severity parameters. These data can be useful to identify high-risk patients who might benefit of AVR.