scholarly journals RyR2 QQ2958 Genotype and Risk of Malignant Ventricular Arrhythmias

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Francesca Galati ◽  
Antonio Galati ◽  
Serafina Massari
Keyword(s):  
Ryanodine Receptor ◽  
Calcium Binding ◽  
Ventricular Arrhythmias ◽  
Receptor Gene ◽  
Developed Countries ◽  
Clinical Variable ◽  
Increased Risk ◽  
Common Causes ◽  
Life Threatening

Ventricular arrhythmias are one of the most common causes of death in developed countries. The use of implantable cardiac defibrillators is the most effective treatment to prevent sudden cardiac death. To date, the ejection fraction is the only approved clinical variable used to determine suitability for defibrillator placement in subjects with heart failure. The purpose of this study was to assess whether genetic polymorphisms found in the ryanodine receptor type 2 (Q2958R) and histidine-rich calcium-binding protein (S96A) might serve as markers for arrhythmias. Genotyping was performed in 235 patients treated with defibrillator for primary and secondary prevention of arrhythmias. No significant association was found between the S96A polymorphism and arrhythmia onset, whereas the QQ2958 genotype in the ryanodine receptor gene was correlated with an increased risk of life-threatening arrhythmias. Concurrent stressor conditions, such as hypertension, seem to increase this effect. Our findings might help to better identify patients who could benefit from defibrillator implantation.

scholarly journals Molecular basis for allosteric regulation of the type 2 ryanodine receptor channel gating by key modulators

2019 ◽  
Author(s):  
Ximin Chi ◽  
Deshun Gong ◽  
Kang Ren ◽  
Gewei Zhou ◽  
Gaoxingyu Huang ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ryanodine Receptor ◽  
Molecular Basis ◽  
Central Domain ◽  
Mechanistic Insight ◽  
Life Threatening ◽  
Cardiac Disorders ◽  
Insight Into ◽  
Receptor Channel

AbstractThe type-2 ryanodine receptor (RyR2) is responsible for releasing Ca2+ from the sarcoplasmic reticulum of cardiomyocytes, subsequently leading to muscle contraction. Here, we report four cryo-EM structures of porcine RyR2 bound to distinct modulators that collectively provide mechanistic insight into RyR2 regulation. Ca2+ alone induces a contraction of the Central domain that facilitates the dilation of S6 bundle, but is insufficient to open the pore. The small molecule agonist PCB95 helps Ca2+ to overcome the barrier for opening. FKBP12.6 induces a relaxation of the Central domain that decouples it from the S6 bundle, stabilizing RyR2 in a closed state. Caffeine locks the Central domain in a constitutively contracted state, while further addition of ATP opens the channel by strengthening the coupling between the U-motif and S6. Our study marks an important step towards mechanistic understanding of the complicated regulation of this key channel whose aberrant activity engenders life-threatening cardiac disorders.

scholarly journals Inhalatory and intravenous colistin in treating ventilator-associated pneumonia due to acinetobacter species: Should we combine them?

2020 ◽  
Vol 77 (8) ◽  
pp. 832-838
Author(s):  
Jovan Matijasevic ◽  
Srdjan Gavrilovic ◽  
Ilija Andrijevic ◽  
Ana Andrijevic ◽  
Svetislava Milic ◽  
...  
Keyword(s):  
Nosocomial Infections ◽  
Demographic Data ◽  
Multidrug Resistant ◽  
Acinetobacter Species ◽  
Risk Of Death ◽  
Increased Risk ◽  
Inhaled Antibiotics ◽  
Common Causes ◽  
Life Threatening ◽  
Severity Of The Disease

Background/Aim. Acinetobacter is one of the most common causes of nosocomial infections, especially ventilatorassociated pneumonia (VAP). Considering the increased presence of multidrug-resistant microorganisms and the lack of novel antibiotics, colistin merged as the last-resort antibiotic for life threatening nosocomial infections. Intravenous use of antibiotics is accepted as a gold standard for the treatment of pneumonia, but additional administration of inhaled antibiotics in the treatment of VAP has shown to be advantageous in some clinical trials. The aim of this study was to investigate the effect of inhalatory colistin as an adjunct to intravenous colistin on the survival of patients with VAP caused by Acinetobacter species. Methods. We conducted a retrospective study to evaluate the efficacy of combination of inhalatory and intravenous colistin vs. intravenous colistin alone in 69 patients in the Intensive Care Units (ICU) with VAP caused by Acinetobacter baumannii. The patients were treated in the ICU at the Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica (Serbia) in the period from January, 2013 to March, 2018. Baseline demographic data, severity of the disease, comorbidities, colistin regimen and length of the treatment were collected. The primary outcome was 28-day mortality. Results. Twenty seven of total 69 (39.1%) patients received combined intravenous and inhalatory colistin. Forty two (60.9%) patients received only intravenous colistin. Compared to the combined use of the drug (intravenous and inhalatory colistin), patients receiving intravenous colistin alone had a significantly increased risk of death during 28 days [25.9% vs. 61.9%, respectively; odds ratio (OR) 4.464, 95% confidence interval (CI) 1.539?2.925; p = 0.006]. Length of colistin use (> 7 days) was also associated with reduced survival (OR 0.22; 95% CI 0.080?0.606; p = 0.003). After adjusting for baseline severity of the illness (APACHE score) and length of colistin treatment, patients receiving only intravenous colistin had greater 28-day mortality rate compared to patients receiving both intravenous and inhalatory colistin (OR 6.305; 95% CI 1.795?22.153; p = 0.004). Conclusion. Our results suggest that adding inhalatory to intravenous colistin might be beneficial in the treatment of VAP caused by Acinetobacter species.

Abstract 14117: Clinical Characteristics and Cardiovascular Outcomes in Childhood-Onset Hypertrophic Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nicholas A Marston ◽  
Larry Han ◽  
iacopo olivotto ◽  
Sharlene Day ◽  
Euan A Ashley ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Ventricular Arrhythmias ◽  
Composite Endpoint ◽  
Adult Onset ◽  
Childhood Onset ◽  
Ventricular Assist ◽  
Disease Biology ◽  
Increased Risk ◽  
Age Of Diagnosis ◽  
Life Threatening

Introduction: The prevalence of childhood-onset hypertrophic cardiomyopathy (HCM) is lower than adult-onset disease, thus natural history is not well characterized. We aim to describe the characteristics and outcomes of childhood-onset HCM. Methods: We performed an observational cohort study of 6345 HCM patients from the Sarcomeric Human Cardiomyopathy Registry (SHaRe) and Toronto's SickKids hospital. HCM patients were stratified by age at diagnosis (<1 year (infancy), 1-18 years (childhood), >18 years (adulthood)) and assessed for composite endpoints reflecting heart failure (HF), life-threatening ventricular arrhythmias, atrial fibrillation (AF), and an overall composite that also included stroke and death. Results: Based on defined age of diagnosis stratification, 173 (3%) patients were diagnosed in infancy, 909 (14%) in childhood, and 5263 (83%) in adulthood. Childhood-onset HCM patients had a 2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the 1st decade following diagnosis, and HF and AF more common by the end of the 2nd decade ( Fig, a ). Sarcomeric HCM was more common in childhood-onset HCM (62%) and carried a worse prognosis than non-sarcomeric disease, including a >2-fold increased risk of HF (HR adj 2.39 [1.36-4.20], p=0.003) and 67% increased risk of overall composite events (HR adj 1.67 [1.16-2.41], p=0.006). When compared to adult-onset HCM, childhood-onset was 36% more likely to develop life-threatening ventricular arrhythmias (HR adj 1.36 [1.03-1.80]) and twice as likely to require transplant or ventricular assist device (HR adj 1.99 [1.23-3.23]) ( Fig, b ). Conclusion: Patients with childhood-onset HCM are more likely to have sarcomeric disease, carry higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. These findings provide insight into disease biology and can help improve the precision of risk prediction.

Complex atrial arrhythmias as first manifestation of catecholaminergic polymorphic ventricular tachycardia: an unusual course in a patient with a new mutation in ryanodine receptor type 2 gene

2013 ◽  
Vol 24 (4) ◽  
pp. 741-744 ◽  
Author(s):  
Wolfgang Lawrenz ◽  
Otto N. Krogmann ◽  
Marcus Wieczorek
Keyword(s):  
Ventricular Tachycardia ◽  
Ryanodine Receptor ◽  
Sinus Node ◽  
Catecholaminergic Polymorphic Ventricular Tachycardia ◽  
Receptor Type ◽  
Polymorphic Ventricular Tachycardia ◽  
Atrial Arrhythmias ◽  
Initial Manifestation ◽  
Life Threatening

AbstractCatecholaminergic polymorphic ventricular tachycardia is a rare life-threatening arrhythmogenic disorder. An association with paroxysmal atrial fibrillation and other atrial arrhythmias has been described, but in all published cases the initial manifestation of the disease was ventricular arrhythmia. This is the first report about a patient who presented with complex atrial tachycardia and sinus node dysfunction about 1 year before the typical ventricular arrhythmias were observed, leading to the diagnosis of catecholaminergic polymorphic ventricular tachycardia. In this girl, a mutation of the ryanodine receptor type 2 gene, which has not been described so far, was discovered.

A novel ryanodine receptor expressed in pancreatic islets by alternative splicing from type 2 ryanodine receptor gene

2010 ◽  
Vol 397 (2) ◽  
pp. 140-145 ◽  
Author(s):  
Shin Takasawa ◽  
Michio Kuroki ◽  
Koji Nata ◽  
Naoya Noguchi ◽  
Takayuki Ikeda ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Pancreatic Islets ◽  
Ryanodine Receptor ◽  
Receptor Gene

scholarly journals Follow-Up with Exercise Test of Effort-Induced Ventricular Arrhythmias Linked to Ryanodine Receptor Type 2 Gene Mutations

2012 ◽  
Vol 109 (7) ◽  
pp. 1015-1019 ◽  
Author(s):  
Alexandros Klavdios Steriotis ◽  
Andrea Nava ◽  
Alessandra Rampazzo ◽  
Cristina Basso ◽  
Gaetano Thiene ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Exercise Test ◽  
Ventricular Arrhythmias ◽  
Gene Mutations ◽  
Receptor Type

scholarly journals Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy

2021 ◽  
Author(s):  
Nicholas A Marston ◽  
Larry Han ◽  
Iacopo Olivotto ◽  
Sharlene M Day ◽  
Euan A Ashley ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Natural History ◽  
Ventricular Arrhythmias ◽  
Composite Endpoint ◽  
Adult Onset ◽  
Childhood Onset ◽  
Ventricular Assist ◽  
Increased Risk ◽  
Age Of Diagnosis ◽  
Life Threatening

Abstract Aims Childhood-onset hypertrophic cardiomyopathy (HCM) is far less common than adult-onset disease, thus natural history is not well characterized. We aim to describe the characteristics and outcomes of childhood-onset HCM. Methods and results We performed an observational cohort study of 7677 HCM patients from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Hypertrophic cardiomyopathy patients were stratified by age at diagnosis [&lt;1 year (infancy), 1–18 years (childhood), &gt;18 years (adulthood)] and assessed for composite endpoints reflecting heart failure (HF), life-threatening ventricular arrhythmias, atrial fibrillation (AF), and an overall composite that also included stroke and death. Stratifying by age of diagnosis, 184 (2.4%) patients were diagnosed in infancy; 1128 (14.7%) in childhood; and 6365 (82.9%) in adulthood. Childhood-onset HCM patients had an ∼2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the 1st decade following baseline visit, but HF and AF becoming more common by the end of the 2nd decade. Sarcomeric variants were more common in childhood-onset HCM (63%) and carried a worse prognosis than non-sarcomeric disease, including a greater than two-fold increased risk of HF [HRadj 2.39 (1.36–4.20), P = 0.003] and 67% increased risk of the overall composite outcome [HRadj 1.67 (1.16–2.41), P = 0.006]. When compared with adult-onset HCM, childhood-onset was 36% more likely to develop life-threatening ventricular arrhythmias [HRadj 1.36 (1.03–1.80)] and twice as likely to require transplant or ventricular assist device [HRadj 1.99 (1.23–3.23)]. Conclusion Patients with childhood-onset HCM are more likely to have sarcomeric disease, carry a higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. These findings provide insight into the natural history of disease and can help inform clinical risk stratification.

scholarly journals Metformin Is Associated with a Lower Risk of Atrial Fibrillation and Ventricular Arrhythmias Compared to Sulfonylureas: An Observational Study

2021 ◽  
Author(s):  
Anna Ostropolets ◽  
Pierre A. Elias ◽  
Michael V. Reyes ◽  
Elaine Y. Wan ◽  
Utpal B. Pajvani ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ventricular Arrhythmias ◽  
Diabetic Patients ◽  
Atrial Arrhythmias ◽  
Metformin Monotherapy ◽  
Increased Risk ◽  
Chronic Disorders ◽  
Reduced Risk

Background - Type 2 diabetes (DM2) is one of the most common chronic disorders worldwide and is an important cause of cardiovascular disease. Studies investigating the risk of atrial and ventricular arrhythmias in diabetic patients taking different oral diabetes medications are sparse. Methods - We used IBM MarketScan® Medicare Supplemental Database to examine the risk of arrhythmias for patients on different oral diabetes medications by propensity score matching. Results - We found that patients on metformin monotherapy had significantly reduced risk of atrial arrhythmias, including atrial fibrillation, compared to monotherapy with DPP4 or TZD medications. Patients on metformin monotherapy had significantly reduced risk of atrial arrhythmias, ventricular arrhythmias, and bradycardia compared to monotherapy with sulfonylureas. Combination therapy with sulfonylureas and metformin had an increased risk of atrial arrhythmias compared to some other combinations. Conclusions - Different oral diabetes medications have significantly different long-term risk of arrhythmia. Specifically, metformin is associated with reduced risk of atrial fibrillation and ventricular arrhythmias compared to sulfonylureas.

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