Sinus Node Dysfunction

Sathnur, Neeraj; Ebin, Emanuel; Benditt, David G.

doi:10.1016/j.ccl.2023.03.013

Cited by 5 publications

(3 citation statements)

References 96 publications

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“…The most common reasons for discontinuation of beta-blockers after discharge in our study population were hypotension and bradycardia. However, there might be a variety of additional reasons including such as worsening of chronic obstructive pulmonary disease and sick sinus syndrome [ 14 ]. A promising finding is that the percentage of patients with SGLT-2 inhibitors increased from 5.4% to 47.2%, which indicates a relatively fast adoption of new medications after inclusion into GDMT.…”

Section: Discussionmentioning

confidence: 99%

Medication and Outcome in Older Heart Failure Patients: Results from a Prospective Cohort Study

Garay,

Saner,

Herzberg

et al. 2024

Pharmaceuticals

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Purpose: Acute heart failure (AHF) is associated with high morbidity and mortality, and the prognosis is particularly poor in older patients. Although the application of guideline-directed medical therapy (GDMT) has shown a positive impact on prognosis, the effects are less clear in older age groups. The aim of this study was to analyze real-world data regarding GDMT and outcomes in older HF patients. Methods: This is a prospective cohort study from a secondary care hospital in central Switzerland. A total of 97 consecutive patients aged ≥60 years were enrolled between January 2019 and 2022. The main outcome parameters were prescribed GDMT at discharge, and in case of rehospitalization, GDMT at readmission, and survival in terms of all-cause mortality and HF-related hospitalizations during a 3-year follow-up period. Results: Follow-up data were available for 93/97 patients. The mean age was 77.8 ± 9.8 years, 46% being female. The mean left ventricular ejection fraction (LVEF) was 35.3 ± 13.9%, with a mean BNP level of 2204.3 ± 239 ng/L. Upon discharge, 86% received beta-blockers and 76.3% received renin–angiotensin system (RAS) inhibitors. At rehospitalization for AHF, beta-blockers use was significantly lower and decreased to 52.8% (p = 0.003), whereas RAS inhibitor use increased slightly to 88.9% (p = 0.07), and SGLT-2 inhibitors showed a significant increase from 5.4% vs. 47.2% (p = 0.04). GDMT prescription was not dependent on LVEF. Overall, 73.1% of patients received two-stage or three-stage GDMT at discharge, whereas this percentage decreased to 61% at rehospitalization (p = 0.01). Kaplan–Meier analysis for the combined outcome rehospitalization and death stratified by LV function showed significant differences between LVEF groups (aHR: 0.6 [95% CI: 0.44 to 0.8]; p = 0.0023). Conclusions: Our results indicate that first, the majority of older AHF patients from a secondary care hospital in Switzerland were not on optimal GDMT at discharge and even fewer at readmission, and second, that prognosis of the population is still poor, with almost half of the patients having been rehospitalized or died during a 3-year follow-up period under real-world conditions, without significant difference between women and men. Our findings underline the need for further improvements in the medical treatment of AHF, in particular in older patients, to improve prognosis and to reduce the burden of disease.

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Section: Discussionmentioning

confidence: 99%

Medication and Outcome in Older Heart Failure Patients: Results from a Prospective Cohort Study

Garay,

Saner,

Herzberg

et al. 2024

Pharmaceuticals

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“…ДСУ чаще всего связана с возрастным прогрессирующим дегенеративным фиброзом ткани синусового узла (СУ) и окружающего предсердного миокарда [3][4][5]. Это может привести к патологии формирования и распространения импульса и может быть связано с различными синдромами брадикардии или паузами.…”

Section: ключевые моменты Key Messagesunclassified

Obstructive sleep apnea in bradyarrhythmias

Bulavina,

Vaisman,

Baimukanov

et al. 2024

Russ J Cardiol

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In recent decades, there has been increased interest in obstructive sleep apnea (OSA), especially in patients with a combination of OSA and sleep bradyarrhythmias. Worldwide, the diagnosis of OSA is steadily increasing. Increasingly, clinicians have begun to use CPAP therapy to treat sleep-related bradyarrhythmias. But in world practice there are no unambiguous guidelines for the management of this group of patients.

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“…Patients with SND show a broad range of clinical symptoms, e.g., dizziness, syncope, fall [3], and it may increase the risk of cardiac arrhythmias [4]. SND may be due to extrinsic or intrinsic factors and both exhibit variable manifestations, as recently reviewed by Sathnur and colleagues [5]. It was increasingly recognized that ion channel dysfunction and inherited forms of so-called channelopathies are an important cause for intrinsic and familial SND resulting in an upcoming list of ion-channel genes being involved in SND (for reviews, see [4,[6][7][8]).…”

Section: Introductionmentioning

confidence: 99%

The W101C KCNJ5 Mutation Induces Slower Pacing by Constitutively Active GIRK Channels in hiPSC-Derived Cardiomyocytes

Kayser,

Dittmann,

Šarić

et al. 2023

IJMS

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Mutations in the KCNJ5 gene, encoding one of the major subunits of cardiac G-protein-gated inwardly rectifying K+ (GIRK) channels, have been recently linked to inherited forms of sinus node dysfunction. Here, the pathogenic mechanism of the W101C KCNJ5 mutation underlying sinus bradycardia in a patient-derived cellular disease model of sinus node dysfunction (SND) was investigated. A human-induced pluripotent stem cell (hiPSCs) line of a mutation carrier was generated, and CRISPR/Cas9-based gene targeting was used to correct the familial mutation as a control line. Both cell lines were further differentiated into cardiomyocytes (hiPSC-CMs) that robustly expressed GIRK channels which underly the acetylcholine-regulated K+ current (IK,ACh). hiPSC-CMs with the W101C KCNJ5 mutation (hiPSCW101C-CM) had a constitutively active IK,ACh under baseline conditions; the application of carbachol was able to increase IK,ACh, further indicating that not all available cardiac GIRK channels were open at baseline. Additionally, hiPSCW101C-CM had a more negative maximal diastolic potential (MDP) and a slower pacing frequency confirming the bradycardic phenotype. Of note, the blockade of the constitutively active GIRK channel with XAF-1407 rescued the phenotype. These results provide further mechanistic insights and may pave the way for the treatment of SND patients with GIRK channel dysfunction.

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Sinus Node Dysfunction

Cited by 5 publications

References 96 publications

Medication and Outcome in Older Heart Failure Patients: Results from a Prospective Cohort Study

Medication and Outcome in Older Heart Failure Patients: Results from a Prospective Cohort Study

Obstructive sleep apnea in bradyarrhythmias

The W101C KCNJ5 Mutation Induces Slower Pacing by Constitutively Active GIRK Channels in hiPSC-Derived Cardiomyocytes

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