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ANP is mainly synthesized by the atria, and upon excretion, it serves two primary purposes: vasodilation and increasing the renal excretion of sodium and water. The understanding of ANP’s role in cardiac systems has improved considerably in recent decades. This review focuses on several studies demonstrating the importance of analyzing the regulations between the endocrine and mechanical function of the heart and emphasizes the effect of ANP, as the primary hormone of the atria, on atrial fibrillation (AF) and related diseases. The review first discusses the available data on the diagnostic and therapeutic applications of ANP and then explains effect of ANP on heart failure (HF) and atrial fibrillation (AF) and vice versa, where tracking ANP levels could lead to understanding the pathophysiological mechanisms operating in these diseases. Second, it focuses on conventional treatments for AF, such as cardioversion and catheter ablation, and their effects on cardiac endocrine and mechanical function. Finally, it provides a point of view about the delayed recovery of cardiac mechanical and endocrine function after cardioversion, which can contribute to the occurrence of acute heart failure, and the potential impact of restoration of the sinus rhythm by extensive ablation or surgery in losing ANP-producing sites. Overall, ANP plays a key role in heart failure through its effects on vasodilation and natriuresis, leading to a decrease in the activity of the renin-angiotensin-aldosterone system, but it is crucial to understand the intimate role of ANP in HF and AF to improve their diagnosis and personalizing the patients’ treatment.

Background Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multisystemic, life-threatening disease resulting from the deposition of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in various tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal, observational study of patients with ATTR amyloidosis, including both hereditary and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This analysis describes the baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2022), providing a consolidated overview of 15-year data from the THAOS registry. Results This analysis included 4428 symptomatic patients and 1707 asymptomatic gene carriers. The majority of symptomatic patients were male (70.8%) with a mean (standard deviation [SD]) age at symptom onset of 56.6 (17.9) years. Compared with the 14-year analysis, V30M remained the most prevalent genotype in Europe (62.2%), South America (78.6%), and Japan (74.2%) and ATTRwt remained most common in North America (56.2%). Relative to the 14-year analysis, there was an increase of mixed phenotype (from 16.6 to 24.5%) and a reduction of predominantly cardiac phenotype (from 40.7 to 31.9%). The proportion of patients with predominantly neurologic phenotype remained stable (from 40.1 to 38.7%). Asymptomatic gene carriers were 58.5% female with a mean age at enrollment of 41.9 years (SD 15.5). Conclusions This overview of > 6000 patients enrolled over 15 years in THAOS represents the largest registry analysis of ATTR amyloidosis to date and continues to emphasize the genotypic and phenotypic heterogeneity of the disease. Nearly a quarter of the symptomatic population within THAOS was mixed phenotype, underscoring the need for multidisciplinary management of ATTR amyloidosis. Trial registration ClinicalTrials.gov Identifier : NCT00628745.

Purpose18F-FDG PET/CT is an emerging technique for diagnosis of cardiac implantable electronic devices infection (CIEDI). Despite the improvements in transvenous lead extraction (TLE), long-term survival in patients with CIEDI is poor. The aim of the present study was to evaluate whether the extension of CIEDI at 18F-FDG PET/CT can improve prediction of survival after TLE.MethodsProspective, monocentric observational study enrolling consecutive candidates to TLE for a diagnosis of CIEDI. 18F-FDG PET/CT was performed in all patients prior TLE.ResultsThere were 105 consecutive patients with confirmed CIEDI enrolled. An increased 18F-FDG uptake was limited to cardiac implantable electrical device (CIED) pocket in 56 patients, 40 patients had a systemic involvement. We had nine negative PET in patients undergoing prolonged antimicrobial therapy (22.5 ± 14.0 days vs. 8.6 ± 13.0 days; p = 0.005). Implementation of 18F-FDG PET/CT in modified Duke Criteria lead to reclassification of 23.8% of the patients. After a mean follow-up of 25.0 ± 9.0 months, 31 patients died (29.5%). Patients with CIED pocket involvement at 18F-FDG PET/CT presented a better survival independently of presence/absence of systemic involvement (HR 0.493, 95%CI 0.240–0.984; p = 0.048). After integration of 18F-FDG PET/CT data, absence of overt/hidden pocket involvement in CIEDI and a (glomerular filtration rate) GFR < 60 ml/min were the only independent predictors of mortality at long term.ConclusionsPatient with CIEDI and a Cold Closed Pocket (i.e., a CIED pocket without skin erosion/perforation nor increased capitation at 18F-FDG PET/CT) present worse long-term survival. Patient management can benefit by systematic adoption of pre-TLE 18F-FDG PET/CT through improved identification of CIED related endocarditis (CIEDIE) and hidden involvement of CIED pocket.

There are conflicting findings from observational studies of the arrhythrogenic potential of azithromycin. Our aim was to quantify the association between azithromycin use and the risk of ventricular arrhythmia. We conducted a nested case–control study within a cohort of new antibiotic users identified from a network of 7 population-based health care databases in Denmark, Germany, Italy, the Netherlands and the United Kingdom for the period 1997–2010. Up to 100 controls per case were selected and matched by age, sex and database. Recency of antibiotic use and type of drug (azithromycin was the exposure of interest) at the index date (occurrence of ventricular arrhythmia) were identified. We estimated the odds of ventricular arrhythmia associated with current azithromycin use relative to current amoxicillin use or nonuse of antibiotics (≥ 365 d without antibiotic exposure) using conditional logistic regression, adjusting for confounders. We identified 14 040 688 new antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed in 12 874, of whom 30 were current azithromycin users. The mean age of the cases and controls was 63 years, and two-thirds were male. In the pooled data analyses across databases, azithromycin use was associated with an increased risk of ventricular arrhythmia relative to nonuse of antibiotics (adjusted odds ratio [OR] 1.97, 95% confidence interval [CI] 1.35–2.86). This increased risk disappeared when current amoxicillin use was the comparator (adjusted OR 0.90, 95% CI 0.48–1.71). Database-specific estimates and meta-analysis confirmed results from the pooled data analysis. Current azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication.

•Polypharmacy and drug-drug interactions (DDIs) increased after direct oral anticoagulant (DOAC) initiation in real-world patients with atrial fibrillation.•Over half of the patients increased the number of interacting drugs after DOAC initiation.•Higher number of DDIs was independently associated with major bleeding.•Dabigatran use and low-dose DOACs were linked to increased bleeding risk.•Findings support the need for personalized DDI risk assessment in DOAC users. Despite their promising safety profile, use of direct oral anticoagulants (DOACs) presents challenges, particularly concerning polypharmacy and potential drug-drug interactions (DDIs). This study aimed to investigate real-world effects of polypharmacy and DDIs among DOAC users, focusing on patients with atrial fibrillation (AF). A retrospective cohort analysis was conducted using administrative health care data from the Caserta Local Health Unit (2012–2020). Incident DOAC users were categorized by type of anticoagulant (apixaban, dabigatran, rivaroxaban, and edoxaban). Polypharmacy and DDIs were analyzed before and after index date (ID), stratifying results by DOAC and therapeutic indication. The impact of DDIs on safety outcomes, particularly bleeding risk, was assessed. Bleeding outcomes were evaluated within 1 year after ID by multivariate regression models. Among 16,367 incident DOAC users, 68.9% were treated for AF. The number of interacting drugs increased in 55.2% of patients, with a higher prevalence of 3+ interacting drugs in low-dose users (35% vs 29.2% in high-dose users; P < 0.05). Before ID, 35.6% of the overall cohort had 0 interacting drugs compared with 15.2% after ID. Dabigatran users had the highest increase in interacting drugs (61.8%) compared with anti-Xa agents (56%). Patients with 6+ interacting drugs exhibited a 2.5% incidence of major bleeding after ID. Dabigatran use and low-dose DOAC regimens were independently associated with increased bleeding risks. Polypharmacy and DDIs are prevalent among real-world DOAC users, particularly in patients with AF. The observed association between DDIs and bleeding risk underscores the importance of personalized medication management strategies and routine DDI evaluations to optimize DOAC safety. [Display omitted]

Cardiac implantable electronic devices infections (CIEDI) are associated with poor survival despite the improvement in transvenous lead extraction (TLE). Aetiology and systemic involvement are driving factors of clinical outcomes. The aim of this study was to explore their contribute on overall mortality. A prospective study was performed between 2011 and 2021, including all TLE candidates at our regional referral University hospital for CIEDI with microbiological confirmed aetiology. Considering significant predictors of mortality at multivariate Cox regression analyses, a 5-point BOP 2 D score was developed, and it was validated with a prospective cohort from the Padua University. 157 patients were enrolled (mean age 71.3 ± 12.3 years, 81.5% male). S. aureus was isolated in 32.5% of patients, and it was more associated with valvular heart disease, systemic infection, and chronic kidney disease. CIEDI pattern was associated with 1-year mortality, with a significantly worse outcome in patients with “cold closed pocket” (CCP). The developed BOP 2 D score presented a 0.807 AUC (95%CI 0.703–0.910, p  < 0.001) and a good predictive value (OR 2.355, 95%CI 1.754–3.162; p  < 0.001), and was associated with a progressive increase in mortality with a score > 2. The score validation with the registry from the Padua University (135 patients) retrieved a C-statistic of 0.746 (95%CI 0.613–0.879; p  = 0.002). Both CCP and S. aureus were confirmed as risk factors for mortality in CIEDI patients. This study supports the hypothesis that the infectious process may occur through different mechanisms associated with different infection patterns, and high-risk patients should be considered for specific and aggressive approaches.

Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multi-systemic disease with wild-type (ATTRwt) and hereditary (ATTRv) forms. Over 130 variants associated with ATTRv amyloidosis have been identified, although little is known about the majority of these genotypes. This analysis examined phenotypic characteristics of symptomatic patients with ATTRv amyloidosis enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS) with four less frequently reported pathogenic genotypes: F64L (c.250T>C, p.F84L), I68L (c.262A>T, p.I88L), I107V (c.379A>G; p.I127V), and S77Y (c.290C>A; p.S97Y). THAOS is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both ATTRwt and ATTRv amyloidosis. This analysis describes the baseline demographic and clinical characteristics of untreated symptomatic patients with the F64L, I68L, I107V, or S77Y genotypes at enrollment in THAOS (data cutoff date: January 4, 2022). There were 141 symptomatic patients with F64L (n = 46), I68L (n = 45), I107V (n = 21), or S77Y (n = 29) variants at the data cutoff. Most patients were male and median age at enrollment was in the sixth decade for S77Y patients and the seventh decade for the others. A predominantly neurologic phenotype was associated with F64L, I107V, and S77Y genotypes, whereas patients with the I68L genotype presented with more pronounced cardiac involvement. However, a mixed phenotype was also reported in a considerable proportion of patients in each variant subgroup. This analysis from THAOS represents the largest study of ATTRv symptomatic patients with the F64L, I68L, I107V, and S77Y genotypes. These data add to the limited knowledge on the clinical profile of patients with specific ATTRv variants and emphasize the importance of comprehensive assessment of all patients. Trial registration ClinicalTrials.gov: NCT00628745 .

Previous RCTs and meta-analyses observed an increased occurrence of atrial fibrillation (AF) associated with ivabradine use. Nonetheless, these studies were not focused on AF diagnosis, and it remains unclear whether this observed increase is due to a direct effect of ivabradine or just an augmented AF detection. The latter mechanism could arise from a greater heart-rate differential between sinus rhythm and AF under ivabradine, potentially intensifying symptoms and prompting earlier clinical evaluation. If this hypothesis is true, an earlier diagnosis of AF, and subsequent earlier prophylaxis with anticoagulants, may result in a reduced incidence of ischemic cerebrovascular events. We conducted a meta-analysis of the existing literature (calculating the ratio between ischemic cerebrovascular events and AF) combined with a disproportionality analysis of individual case safety reports of suspected adverse drug reactions. In the disproportionality analysis, we also included beta-blockers as a comparator group, given their dromotropic effect. From 555 studies screened in the meta-analysis, only three were considered eligible. The ratio between ischemic cerebrovascular events and AF with ivabradine was lower than with placebo (RR 0.74, 95% CI 0.62-0.89; p < 0.001). In the FAERS, AF was disproportionally reported with both ivabradine and beta-blockers (Information Component 0.84, 95% CI 0.43-1.14 and Information Component 0.53, 95% CI 0.44-0.60), while ischemic cerebrovascular events only with beta-blockers (Information Component 0.25, 95% CI 0.18-0.31). Our findings raise the hypothesis that ivabradine facilitates an increased diagnosis rather than playing a direct role in causing AF. Prospective studies with continuous ECG monitoring and standardized endpoints are needed to clarify the temporal and mechanistic relationship between ivabradine, AF recognition, and cerebrovascular risk.

: Cardiac resynchronization therapy with defibrillator (CRT-D) is a well-established therapy for patients with heart failure (HF) and intraventricular conduction delays, but a non-negligible risk of infection and of lead functionality loss overtime is related to intravascular hardware. The novel DX system enables atrial sensing through a floating dipole integrated into the ICD lead, reducing the intravascular burden. In this prospective non-randomized study, we aimed to evaluate the safety and efficacy of a two-lead DX-based CRT system compared to a conventional three-lead (3L) CRT-D system. : A total of 210 patients meeting CRT indications and no signs of sick sinus syndrome (SSS) (baseline HR ≥ 45 bpm, or at least 85 bpm at 6 min walking test) were enrolled. Patients were assigned to either the CRT-DX or conventional 3L CRT-D group. The primary endpoint was a composite clinical response, defined as the freedom from cardiovascular death, HF hospitalization, or new-onset atrial fibrillation (AF). : After a mean follow-up of 46.5 ± 1.9 months, both groups had comparable clinical and instrumental outcomes. CRT-DX patients exhibited higher atrial sensing amplitudes and no significant differences in loss of lead function. In conclusion, the CRT-DX system provides equivalent clinical and echocardiographic benefits compared to conventional CRT-D in patients without an indication for atrial pacing. This supports the use of the DX system as a safe and effective alternative in the majority of CRT recipients.