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Physiological Reports Jul 2024The central role of natriuretic peptides (NPs) in the complex cardio-renal integrated physiology and organ failure has been revealed over the last four decades. Atrial... (Review)
Review
The central role of natriuretic peptides (NPs) in the complex cardio-renal integrated physiology and organ failure has been revealed over the last four decades. Atrial natriuretic peptide (ANP), the oldest representative of the NPs family, is produced through conversion of proANP to the mature peptide by corin, a trans-membrane protease localized to the cardiac myocyte membrane. Similarly, brain natriuretic peptide (BNP) is generated by furin, which cleaves proBNP to BNP in myocytes. Though the components of NPs system, their synthesis and target organs are well established, understanding their role in the interplay between the heart and the kidney is steadily evolving. In this context, Feldman et al. (New England Journal of Medicine, 389, 1685) recently described patients with hypertension, cardiomyopathy, atrial arrhythmia and left atrial fibrosis, associated with a homozygous loss-of-function variant of the gene encoding corin (Cor). Notably, reduced baseline urinary electrolyte and creatinine excretion have been observed in one of the studied patients. This renal excretory functional impairment could be attributed to the lack of cardiac-derived ANP in these patients, as implied by Feldman et al. Yet, in this mini-review we suggest that this aberrant renal manifestation may principally stem from lack of local ANP production at renal tissue, as corin is normally expressed in proximal tubules, Henle's loop and collecting ducts, with locally produced ANP provoking Na and water exertion. Collectively, it seems that beside the classic well-established cardio-renal axis, the renal NPs system functions as local endocrine machinery in the regulation of sodium excretion.
Topics: Humans; Animals; Kidney; Serine Endopeptidases; Atrial Natriuretic Factor; Heart
PubMed: 38942727
DOI: 10.14814/phy2.16105 -
Heart Rhythm Jun 2024The complexity of cardiac electrophysiology procedures has increased significantly over the past three decades. Anesthesia requirements of these procedures can be... (Review)
Review
The complexity of cardiac electrophysiology procedures has increased significantly over the past three decades. Anesthesia requirements of these procedures can be different based on patient- and procedure-specific factors. This manuscript outlines various anesthesia strategies for cardiac implantable electronic devices and electrophysiology procedures including pre-procedural, procedural and post-procedural management. A team-based approach with collaboration between cardiac electrophysiologists and anesthesiologists is required with careful pre-procedural and intra-procedural planning. Given the recent advances in electrophysiology, there is a need for specialized cardiac electrophysiology anesthesia care to improve the efficacy and safety of the procedures.
PubMed: 38942104
DOI: 10.1016/j.hrthm.2024.06.048 -
Journal of Molecular and Cellular... Jun 2024Cardiac arrhythmia treatment is a clinical challenge necessitating safer and more effective therapies. Recent studies have highlighted the role of the perinexus, an...
Cardiac arrhythmia treatment is a clinical challenge necessitating safer and more effective therapies. Recent studies have highlighted the role of the perinexus, an intercalated disc nanodomain enriched in voltage-gated sodium channels including both Na1.5 and β1 subunits, adjacent to gap junctions. These findings offer insights into action potential conduction in the heart. A 19-amino acid SCN1B (β1/β1B) mimetic peptide, βadp1, disrupts VGSC beta subunit-mediated adhesion in cardiac perinexii, inducing arrhythmogenic changes. We aimed to explore βadp1's mechanism and develop novel SCN1B mimetic peptides affecting β1-mediated adhesion. Using patch clamp assays in neonatal rat cardiomyocytes and electric cell substrate impedance sensing (ECIS) in β1-expressing cells, we observed βadp1 maintained inhibitory effects for up to 5 h. A shorter peptide (LQLEED) based on the carboxyl-terminus of βadp1 mimicked this inhibitory effect, while dimeric peptides containing repeated LQLEED sequences paradoxically promoted intercellular adhesion over longer time courses. Moreover, we found a link between these peptides and β1-regulated intramembrane proteolysis (RIP) - a signaling pathway effecting gene transcription including that of VGSC subunits. βadp1 increased RIP continuously over 48 h, while dimeric agonists acutely boosted RIP for up to 6 h. In the presence of DAPT, an RIP inhibitor, βadp1's effects on ECIS-measured intercellular adhesion was reduced, suggesting a relationship between RIP and the peptide's inhibitory action. In conclusion, novel SCN1B (β1/β1B) mimetic peptides are reported with the potential to modulate intercellular VGSC β1-mediated adhesion, potentially through β1 RIP. These findings suggest a path towards the development of anti-arrhythmic drugs targeting the perinexus.
PubMed: 38942073
DOI: 10.1016/j.yjmcc.2024.06.008 -
European Heart Journal Jun 2024
Topics: Humans; Atrial Fibrillation; Climate Change; Obesity
PubMed: 38941334
DOI: 10.1093/eurheartj/ehae380 -
Journal of Addiction Medicine Jun 2024To prospectively assess rates of QT prolongation, arrhythmia, syncope, and sudden cardiac death (SCD) in a cohort of people with heroin dependence.
OBJECTIVES
To prospectively assess rates of QT prolongation, arrhythmia, syncope, and sudden cardiac death (SCD) in a cohort of people with heroin dependence.
METHODS
To estimate rates of QT prolongation, arrhythmia, and syncope, a subcohort (n = 130) from the Australian Treatment Outcomes Study, a prospective longitudinal cohort study of 615 people with heroin dependence, underwent medical history, venepuncture, and ECG at the 18- to 20-year follow-up.To estimate rates of SCD, probabilistic matching for the entire cohort was undertaken with the Australian Institute of Health and Welfare National Death Index. Deaths were classified into suicide, accidental overdose, trauma, unknown, and disease, which were then further subclassified by probability of SCD. SCD rate was the number of possible or probable SCDs divided by total patient years from the cohort.
RESULTS
From the subcohort, 4 participants (3%) met the criteria for QT prolongation; 3 were prescribed methadone. Seven participants (5%) reported history of arrhythmia, including 2 transferred from methadone to buprenorphine. Thirty participants (23%) reported a previous syncopal event-14 diagnosed as nonarrhythmic syncope and 13 not investigated. In the previous 12 months, 66 participants (51%) reported heroin use; 55 participants (42%) were prescribed methadone. No participant had QTc greater than 500 milliseconds.There were 3 possible SCDs, translating to an estimated SCD rate of 0.29 (CI: 0.05, 0.8) events per 1000 patient years. More cohort members died of overdose (n = 50), suicide (n = 11), and hepatitis C (n = 4).
CONCLUSIONS
Low rates of QT prolongation, arrhythmia, syncope, and SCD in the cohort despite high rates of heroin use and methadone treatment.
PubMed: 38941157
DOI: 10.1097/ADM.0000000000001317 -
Journal of the European Academy of... Jun 2024
PubMed: 38940515
DOI: 10.1111/jdv.20184 -
Europace : European Pacing,... Jun 2024To describe the rationale, design, delivery and baseline characteristics of STEEER-AF (Stroke prevention and rhythm control Treatment: Evaluation of an Educational...
Design and deployment of the STEEER-AF trial to evaluate and improve guideline adherence: A cluster-randomised trial by the European Society of Cardiology and European Heart Rhythm Association.
AIMS
To describe the rationale, design, delivery and baseline characteristics of STEEER-AF (Stroke prevention and rhythm control Treatment: Evaluation of an Educational programme of the European Society of Cardiology [ESC] in a cluster-Randomised trial in patients with Atrial Fibrillation).
METHODS & RESULTS
STEEER-AF is a pragmatic trial designed to objectively and robustly determine whether guidelines are adhered to in routine practice, and evaluate a targeted educational programme for healthcare professionals. Seventy centres were randomised in 6 countries (France, Germany, Italy, Poland, Spain and United Kingdom; 2022-2023). STEEER-AF centres recruited 1732 patients with a diagnosis of atrial fibrillation (AF), with mean age 68.9 years (SD 11.7), CHA2DS2-VASc score 3.2 (SD 1.8) and 647 (37%) women. 843 patients (49%) were in AF and 760 (44%) in sinus rhythm at enrolment. Oral anticoagulant therapy was prescribed in 1,543 patients (89%), with the majority receiving direct oral anticoagulants (1,378; 89%). Previous cardioversion, antiarrhythmic drug therapy or ablation was recorded in 836 patients (48.3%). 551 patients (31.8%) were currently receiving an antiarrhythmic drug, and 446 (25.8%) were scheduled to receive a future cardioversion or ablation. The educational programme engaged 195 healthcare professionals across centres randomised to the intervention group, consisting of bespoke interactive online learning and reinforcement activities, supported by national expert trainers.
CONCLUSION
The STEEER-AF trial was successfully deployed across six European countries to investigate guideline adherence in real-world practice, and evaluate if a structured educational programme for healthcare professionals can improve patient-level care.
REGISTRATION
Clinicaltrials.gov NCT04396418.
PubMed: 38940494
DOI: 10.1093/europace/euae178 -
Journal of Extracellular Vesicles Jul 2024Cardiac fibrosis is a common pathological feature of cardiovascular diseases that arises from the hyperactivation of fibroblasts and excessive extracellular matrix (ECM)...
Cardiac fibrosis is a common pathological feature of cardiovascular diseases that arises from the hyperactivation of fibroblasts and excessive extracellular matrix (ECM) deposition, leading to impaired cardiac function and potentially heart failure or arrhythmia. Extracellular vesicles (EVs) released by cardiomyocytes (CMs) regulate various physiological functions essential for myocardial homeostasis, which are disrupted in cardiac disease. Therefore, healthy CM-derived EVs represent a promising cell-free therapy for the treatment of cardiac fibrosis. To this end, we optimized the culture conditions of human adult CMs to obtain a large yield of EVs without compromising cellular integrity by using a defined combination of small molecules. EVs were isolated by ultracentrifugation, and their characteristics were analysed. Finally, their effect on fibrosis was tested. Treatment of TGFβ-activated human cardiac fibroblasts with EVs derived from CMs using our culture system resulted in a decrease in fibroblast activation markers and ECM accumulation. The rescued phenotype was associated with specific EV cargo, including multiple myocyte-specific and antifibrotic microRNAs, although their effect individually was not as effective as the EV treatment. Notably, pathway analysis showed that EV treatment reverted the transcription of activated fibroblasts and decreased several signalling pathways, including MAPK, mTOR, JAK/STAT, TGFβ, and PI3K/Akt, all of which are involved in fibrosis development. Intracardiac injection of CM-derived EVs in an animal model of cardiac fibrosis reduced fibrotic area and increased angiogenesis, which correlated with improved cardiac function. These findings suggest that EVs derived from human adult CMs may offer a targeted and effective treatment for cardiac fibrosis, owing to their antifibrotic properties and the specificity of cargo.
Topics: Myocytes, Cardiac; Humans; Extracellular Vesicles; Fibrosis; Fibroblasts; Animals; MicroRNAs; Extracellular Matrix; Signal Transduction; Transforming Growth Factor beta; Cells, Cultured; Mice; Adult
PubMed: 38940266
DOI: 10.1002/jev2.12461 -
Journal of Cardiovascular... Jun 2024
PubMed: 38940237
DOI: 10.1111/jce.16351 -
Circulation Jun 2024Current estimates of atrial fibrillation (AF)-associated mortality rely on claims- or clinical-derived diagnoses of AF, limit AF to a binary entity, or are confounded by...
BACKGROUND
Current estimates of atrial fibrillation (AF)-associated mortality rely on claims- or clinical-derived diagnoses of AF, limit AF to a binary entity, or are confounded by comorbidities. The objective of the present study is to assess the association between device-recognized AF and mortality among patients with cardiac implantable electronic devices capable of sensitive and continuous atrial arrhythmia detection. Secondary outcomes include relative mortality among cohorts with no AF, paroxysmal AF, persistent AF, and permanent AF.
METHODS
Using the deidentified Optum Clinformatics US claims database (2015 to 2020) linked to the Medtronic CareLink database, we identified individuals with a cardiac implantable electronic device who transmitted data ≥6 months after implantation. AF burden was assessed during the first 6 months after implantation (baseline period). Subsequent mortality, assessed from claims data, was compared between patients with and those without AF, with adjustment for age, geographic region, insurance type, Charlson Comorbidity Index, and implantation year.
RESULTS
Of 21 391 patients (age, 72.9±10.9 years; 56.3% male) analyzed, 7798 (36.5%) had device-recognized AF. During a mean of 22.4±12.9 months (median, 20.1 [12.8-29.7] months) of follow-up, the overall incidence of mortality was 13.5%. Patients with AF had higher adjusted all-cause mortality than patients without AF (hazard ratio, 1.29 [95% CI, 1.20-1.39]; <0.001). Among those with AF, patients with nonparoxysmal AF had the greatest risk of mortality (persistent AF versus paroxysmal AF: hazard ratio, 1.36 [95% CI, 1.18-1.58]; <.001; permanent AF versus paroxysmal AF: hazard ratio, 1.23 [95% CI, 1.14-1.34]; <.001).
CONCLUSIONS
After adjustment for potential confounding factors, presence of AF was associated with higher mortality than no AF in our cohort of patients with cardiac implantable electronic devices. Among those with AF, nonparoxysmal AF was associated with the greatest risk of mortality.
PubMed: 38940005
DOI: 10.1161/CIRCULATIONAHA.124.069757