Is sodium current present in human sinoatrial node cells?

Pacemaker activity of the sinoatrial node has been studied extensively in various animal species, but is virtually unexplored in man. As such, it is unknown whether the fast sodium current (INa) plays a role in the pacemaker activity of the human sinoatrial node. Recently, we had the unique opportunity to perform patch-clamp experiments on single pacemaker cells isolated from a human sinoatrial node. In 2 out of the 3 cells measured, we observed large inward currents with characteristics of INa. Although we were unable to analyze the current in detail, our findings provide strong evidence that INa is present in human sinoatrial node pacemaker cells, and that this INa is functionally available at potentials negative to -60 mV

Risk of out-of-hospital cardiac arrest in patients with epilepsy and users of antiepileptic drugs

Aims: A few studies suggested that epilepsy and antiepileptic drugs with sodium channel-blocking properties were independently associated with out-of-hospital cardiac arrest (OHCA). However, these findings have not yet been replicated. Methods: Using Danish registries, we conducted a nested case–control study in a cohort of individuals between 1 June 2001 and 31 December 2015. Cases were defined as OHCA from presumed cardiac causes, and were matched with non-OHCA-controls based on sex, and age on the date of OHCA. Exposure of interest was epilepsy or antiepileptic drug use. To study the association between individual antiepileptic drug use and the rate of OHCA, we compared each antiepileptic drug with valproic acid. Cox regression with time-dependent covariates was conducted to calculate hazard ratio (HR) and 95% confidence interval (CI). Results: We identified 35 195 OHCA-cases and 351 950 matched non-OHCA controls. Epilepsy (cases: 3.58%, controls: 1.60%) was associated with increased rate of OHCA compared with the general population (HR: 1.76, 95%CI: 1.64–1.88) when common OHCA risk factors were taken into account. When we studied antiepileptic drug use, we found that 2 antiepileptic drugs without sodium channel blockage, clonazepam (HR: 1.88, 95%CI: 1.45–2.44) and pregabalin (HR: 1.33, 95%CI: 1.05–1.69), were associated with OHCA, whereas none of the antiepileptic drugs with sodium channel blockage were associated with OHCA. Conclusion: Epilepsy is associated with increased rate of OHCA. Our findings do not support a possible association between antiepileptic drugs with sodium channel-blocking properties and OHCA

Low rate of cardiac events in first-degree relatives of diagnosis-negative young sudden unexplained death syndrome victims during follow-up

BACKGROUND: Sudden unexplained death syndrome (SUDS) in young individuals often results from inherited cardiac disease. Accordingly, comprehensive examination in surviving first-degree relatives unmasks such disease in approximately 35% of the families. It is unknown whether individuals from diagnosis-negative families are at risk of developing manifest disease or cardiac events during follow-up.OBJECTIVE: This study aimed to study the prognosis of first-degree relatives of young SUDS victims, in whom the initial cardiologic and genetic examination did not lead to a diagnosis.METHODS: We retrieved vital status of surviving first-degree relatives from 83 diagnosis-negative families who presented to our cardiogenetics department between 1996 and 2009 because of SUDS in ≥1 relatives aged 1-50 years. Moreover, we contacted relatives who previously visited our center for detailed information.RESULTS: We obtained detailed information (median follow-up 6.6 years; interquartile range 4.7-9.6 years) in 340 of 417 first-degree relatives (81.5%) from 77 of 83 families (92.8%). Vital status, available in 405 relatives (97.1%), showed that 20 relatives (4.9%) died during follow-up, including 1 natural death before the age of 50. This girl belonged to a family with multiple cases of idiopathic ventricular fibrillation and SUDS, including another successfully resuscitated sibling during follow-up. Two hundred thirty-four of 340 first-degree relatives (68.8%) underwent cardiologic examination. Of these, 76 (32.5%) were reevaluated. Inherited cardiac disease was diagnosed in 3 families (3.6%).CONCLUSION: In first-degree relatives of young SUDS victims with no manifest abnormalities during the initial examination, the risk of developing manifest inherited cardiac disease or cardiac events during follow-up is low. This does not apply to families with obvious familial SUDS.</p

Use of antihypertensive agents and the risk of out-of-hospital cardiac arrest: A case control study

Background: Sudden cardiac arrest (SCA) is a complex multifactorial condition and is commonly caused by ventricular tachycardia/fibrillation (VT/VF). Some antihypertensive agents such as thiazides are associated with increased risk of SCA. Objectives: The aim of this study was to assess the association between different antihypertensive agents and the occurrence of out-of-hospital cardiac arrest (OHCA), taking into account their potential impact on serum potassium levels. Methods: Cases were drawn from the Amsterdam Resuscitation Studies (ARREST) registry and controls from the PHARMO database. This study was performed using 1948 cases who had OHCA with electrocardiogram (ECG)-documented VT/VF for the first time. These cases were matched by age, sex, and OHCA date (index date) to 8347 controls. From this dataset, we included only patients who were current users of antihypertensive agents (the index date fell between start date and end date of prescription + 10%). Antihypertensive therapies were classified according to their potential impact on serum potassium levels to therapies with neutral effect, therapies inducing hypokalemia, therapies inducing hyperkalemia, and therapies with unknown effect. Logistic regression analysis was used to study the association between use of antihypertensive agents and occurrence of OHCA and to control for confounding. Results: We included 1192 cases and 3303 controls who were current users of antihypertensive agents in our analysis. The risk of OHCA was significantly increased with users of antihypertensive therapies inducing hypokalemia (adjusted OR 1.48, 95%CI (1.12- 1.94)) and with users of antihypertensive therapies with unknown effect (adjusted OR 1.42, 95%CI (1.13-1.77)) versus users of antihypertensive therapies with neutral effect. There was no difference in OHCA risk between users of antihypertensive therapies inducing hyperkalemia versus users of antihypertensive therapies with neutral effect (adjusted OR 1.13, 95%CI (0.89-1.43)). Conclusions: The risk of OHCA is significantly increased in patients who were current users of antihypertensive therapies inducing hypokalemia and antihypertensive therapies with unknown effect on serum potassium levels

Opioid use is associated with increased out-of-hospital cardiac arrest risk among 40,000-cases across two countries

AIMS: Opioid use has substantially increased in the last decade and is associated with overdose mortality, but also with increased mortality from cardiovascular causes. This finding may partly reflect an association between opioids and out‐of‐hospital cardiac arrest (OHCA). Therefore, we aimed to investigate OHCA‐risk of opioids in the community. METHODS: We conducted 2 population‐based case–control studies separately in the Netherlands (2009–2018) and Denmark (2001–2015). Cases were individuals who experienced OHCA of presumed cardiac cause. Each case was matched with up to 5 non‐OHCA‐controls according to age, sex and OHCA‐date. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 5473 OHCA‐cases matched with 21 866 non‐OHCA‐controls in the Netherlands, and 35 017 OHCA‐cases matched with 175 085 non‐OHCA‐controls in Denmark. We found that use of opioids (the Netherlands: cases: 5.4%, controls: 1.8%; Denmark: cases: 11.9%, controls: 4.4%) was associated with increased OHCA‐risk in both regions (the Netherlands: OR 2.1 [95% CI 1.8–2.5]; Denmark: OR 1.8 [95% CI 1.5–2.1]). The association was observed in both sexes, and in individuals with cardiovascular disease (the Netherlands: OR 1.8 [95% CI 1.5–2.1]; Denmark: OR 1.6 [95% CI 1.5–1.7]) or without (the Netherlands: OR 3.4 [95% CI: 2.4–4.8], P (interaction) < .0001; Denmark: OR 2.3 [95% CI: 2.0–2.5], P (interaction) < .0001). CONCLUSION: Use of opioids is associated with increased OHCA‐risk in both sexes, independently of concomitant cardiovascular disease. These findings should be considered when evaluating the harms and benefits of treatment with opioids

First-response treatment after out-of-hospital cardiac arrest:a survey of current practices across 29 countries in Europe

Background: In Europe, survival rates after out-of-hospital cardiac arrest (OHCA) vary widely. Presence/absence and differences in implementation of systems dispatching First Responders (FR) in order to arrive before Emergency Medical Services (EMS) may contribute to this variation. A comprehensive overview of the different types of FR-systems used across Europe is lacking. Methods: A mixed-method survey and information retrieved from national resuscitation councils and national EMS services were used as a basis for an inventory. The survey was sent to 51 OHCA experts across 29 European countries. Results: Forty-seven (92%) OHCA experts from 29 countries responded to the survey. More than half of European countries had at least one region with a FR-system. Four categories of FR types were identified: (1) firefighters (professional/voluntary); (2) police officers; (3) citizen-responders; (4) others including off-duty EMS personnel (nurses, medical doctors), taxi drivers. Three main roles for FRs were identified: (a) complementary to EMS; (b) part of EMS; (c) instead of EMS. A wide variation in FR-systems was observed, both between and within countries. Conclusions: Policies relating to FRs are commonly implemented on a regional level, leading to a wide variation in FR-systems between and within countries. Future research should focus on identifying the FR-systems that most strongly influence survival. The large variation in local circumstances across regions suggests that it is unlikely that there will be a 'one-size fits all' FR-system for Europe, but examining the role of FRs in the Chain of Survival is likely to become an increasingly important aspect of OHCA research