Overview

This trial is active, not recruiting.

Conditions out-of-hospital cardiac arrest, ventricular fibrillation
Treatments group 1, group 2, group 3, group 4
Sponsor Helse Stavanger HF
Start date January 2007
End date December 2010
Trial size 77 participants
Trial identifier NCT02886273, StavangerSCA

Summary

Sudden cardiac death (SCD) accounts for approximately 15 percent of the total mortality in industrialized countries, and most commonly results from cardiac arrest due to ventricular fibrillation (VF). VF can appear both with identifiable heart disease and as an idiopathic arrhythmia. The most commonly underlying heart disease associated with out-of-hospital cardiac arrest (OHCA) is coronary artery disease (CAD).

In this study the investigators intend to give a thorough description of the study population based on demographic data, clinical information, medical history and biochemical parameters. The investigators plan to assess the total number of OHCA cases among patients reported to the ambulance service in the local region during the study period, and determine the proportion with documented VF. Next the investigators need to evaluate the clinical baseline profile of those included in the study as compared to that of the total VF population. High sensitivity cardiac Troponin T cTnT) and brain natriuretic peptide (BNP) will be added to the baseline data for further classification of the included SCA patients.

The main aim of the study will be to evaluate the diagnostic value of copeptin in the setting of sudden cardiac arrest (SCA).

As a second aim the investigators intend to evaluate the association between VF and the content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in red blood cells.

Furthermore, as vitamin D is associated with n-3 fatty polyunsaturated acids (n-3 PUFAs) in the diet, the third aim will be to assess the association between 25-hydroxy (OH)-vitamin D and VF. Matched MI patients will be selected for comparison.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Observational model cohort
Time perspective prospective
Arm
SCA with first MI (n = 43)
group 1
Observation
SCA with recurrent MI (n = 10)
group 2
Observation
SCA with no MI and without former heart disease (n = 3)
group 3
Observation
SCA with established heart disease and without acute MI (n = 18)
group 4
Observation

Primary Outcomes

Measure
Early diagnostic performance of copeptin in Out-of-Hospital Cardiac arrest (OHCA) due to ventricular fibrillation (VF)
time frame: 48 hours

Secondary Outcomes

Measure
EPA and DHA as compared to other fatty acids in red blood cell membranes from patients with OHCA
time frame: 48 hours
25-hydroxy (OH)-vitamin D in subjects with OHCA due to ventricular fibrillation (VF)
time frame: 48 hours
Survival rate in OHCA with documented ventricular fibrillation
time frame: 1 month

Eligibility Criteria

Male or female participants of any age.

Inclusion Criteria: 1. Age > 18 years 2. Cardiac etiology 3. Documented recordings demonstrating ventricular fibrillation (VF) Exclusion Criteria: 1. OHCA with primary asystoli 2. Evidence of non-cardiac death (including cerebral etiology and pulmonary embolism) 3. OHCA due to cardiac tamponade.

Additional Information

Official title DIagnostics, RBC Levels of n-3 Fatty Acids and Serum Vitamin D in Patients With Out-of-Hospital Cardiac Arrest (OHCA)
Principal investigator Dennis WT Nilsen, MDd PhD
Description Background: Sudden cardiac death (SCD), also termed sudden cardiac arrest (SCA), accounts for approximately 15 percent of the total mortality in industrialized countries, and most commonly results from cardiac arrest due to ventricular fibrillation (VF). VF can appear both with identifiable heart disease and as an idiopathic arrhythmia. The most commonly underlying heart disease associated with out-of-hospital cardiac arrest (OHCA) is coronary artery disease (CAD). The proportion of OHCA-patients with CAD varies with age. Autopsy studies of subjects under the age of 45 with a presumed diagnosis of SCD have revealed 10-15 percent without any demonstrable cardiac abnormality (1-3). A lower value of about 5 percent is obtained when older patients are included (4). SCD is the initial presentation of CAD in 15 percent of CAD-patients (5). Furthermore it is also the most frequent mechanism of death in patients with known CAD, accounting for 40-50 percent of CAD-mortality (6). Compared to healthy subjects the incidence of SCD is six- to tenfold higher in the presence of clinically recognized heart disease, increases with age and is two to three times as common in men as in women (7). SCD due to VF may appear as the initial presentation of an episode of myocardial ischemia for both patients with and without known CAD. High-sensitivity cardiac Troponin T (hs-cTnT) is the most commonly used marker of myocardial necrosis. Despite increased sensitivity of cardiac troponins (cTn) at an early diagnostic stage with the introduction of hs-cTNT assays, there remains a troponin-blind period very early after symptom onset. Cardiac pulmonary resuscitation itself may also lead to a slight elevation of cardiac markers, including cTn (8). This makes it difficult to use hs-cTNT alone for the diagnosis of acute myocardial infarction (AMI) among patients with OHCA. Copeptin, the C-terminal moiety of provasopressin, is co-secreted with vasopressin. Lately, circulating copeptin levels have been demonstrated to be significantly elevated during the initial acute phase in patients with AMI (9). Its concentration seems to rise immediately after symptom onset and decreases rapidly thereafter. Copeptin may therefore improve early diagnosis of AMI (10-13) and help to differentiate the underlying cause of SCD. When emergency care systems provide early cardiopulmonary resuscitation and defibrillation, approximately 50 percent of out-of-hospital VF patients survive to hospital admission and 25 percent survive to leave the hospital (2, 14). These dramatic consequences make it most important to identify risk factors and also form the rationale for primary prevention. Most interventions to date do not directly affect the transient pathophysiologic event initializing potentially fatal arrhythmias. Instead, they attempt to alter and prevent underlying disease like CAD. Animal studies have shown that fish oils are protective against ischemia-induced VF (15). Support for these data comes from the Physicians`Health Study (16), which is a prospective study of 20 551 men aged 40 to 84, free of cardiovascular disease at baseline, with a follow-up period of 11 years. As compared to consumption of fish less than once a month, fish intake at least once per week was associated with a reduced risk of SCD (RR 0.48). In the same study there was no reduction in the risk of total myocardial infarction, non-sudden cardiac death or total cardiovascular mortality, and the protective effect of fish was suggested to be due to a reduction in fatal ventricular arrhythmias. It has been hypothesized that the lower risk of SCD with higher fish intake may be related to the long-chain n-3 polyunsaturated fatty acids (PUFAs) EPA and DHA found in fish. Consistent with this hypothesis are the observations from the Physicians`Health Study that the risk of SCD was significantly lower in subjects with blood n-3 FA levels in the highest as compared to the lowest quartile. The same potential effect of fish oils to protect against SCD was illustrated in the randomized, open-controlled GISSI-prevention study of 11 324 patients with a recent myocardial infarction (17). Patients receiving n-3 FAs supplements had a significant lower incidence in the combined endpoint of death plus nonfatal infarction and nonfatal stroke at 42 months (12.6 versus 13.9%). After adjustment for risk factors, all of the observed benefit was due to a 20 % reduction in the risk of death, mostly due to reduction in SCD. However, a study of 200 patients secured with an ICD (implantable cardioverter defibrillator) following an episode of ventricular tachycardia (VT) or VF, has not shown a reduction in the recurrence of these arrhythmias after supplementation with EPA/DHA. In that study there was actually a trend toward a higher incidence of VT/VF in patients randomized to EPA/ DHA substitution (18). In that setting the underlying mechanism for the generation of VF might, however, not be ischemic. The exact mechanism by which FAs might protect against serious cardiac arrhythmias is not known. The investigators do know that they are important constituents of cell membranes and may affect several electrophysiologic properties, such as resting potential, action potential, repolarization and refractory period. Alterations in cellular calcium concentration can contribute significantly to changes in both impulse generation and impulse conduction in myocardial cells. Incorporation of n-3 fatty acids in the cellular membrane is shown to affect membrane fluidity which in turn may have an influence on calcium entry or removal. An alternative mechanism may be changes effected by n-3 FAs on myocardial production of eicosanoids. In particular the inhibition of thromboxane A2 (TXA2) production is likely to be of significant pathophysiological benefit, since TXA2 is shown to be implicated in myocardial ischemia and arrhythmogenesis (19). Over the last years vitamin D is another dietary supplement found to be associated with cardiovascular disease. This fat-soluble vitamin, primarily derived from sun-exposure and fatty fish, has been demonstrated to influence cardiac contractility and myocardial calcium homeostasis (20), and insufficiency of this vitamin may have deleterious effects on cardiac autonomic functions as evaluated by heart rate turbulence and heart rate variability (21). In prospective studies, severe vitamin D deficiency has been strongly associated with total mortality, cardiovascular events and SCD (22 - 26). In one study of 3299 Caucasian patients who were routinely referred to coronary angiography, the authors could demonstrate hazard ratios for death due to heart failure and for SCD of 2.84 (1.20-6.74) and 5.05 (2.13-11.97), respectively, when comparing patients with severe vitamin D deficiency [25(OH)D <25 nmol/liter)] with persons in the optimal range [25(OH)D ≥ 75 nmol/liter] (27). Demonstrated effects on electrophysiology, contractility, and cardiac structure suggest that vitamin D deficiency might actually be a causal factor for development of cardiac diseases. The pronounced effect on SCD found in several studies might be an indication of a possible protective effect of high vitamin D-levels against ventricular arrhythmias. This is, however, not well studied and the optimal cut-off-value for protection is not well defined. A recent study by William S. Harris et al (28) has shown that levels of EPA/ DHA in cell membranes of red blood cells (RBC EPA/ DHA) highly correlate with the cardiac EPA/ DHA level. The RBC response to supplementation was also very similar to that observed in the heart. Therefore RBC EPA+ DHA may serve as a useful surrogate of cardiac omega-3 fatty acid status. The investigators expect n-3 FAs to exert a membrane stabilizing effect during an ischemic episode, and hypothesize that patients suffering VF during the initial phase of their first AMI presentation have lower levels of RBC EPA/ DHA than matched controls. As compared to the suggested pro-arrhythmic effects of n-3 FAs during ischemia, vitamin D deficiency may act differently in this respect. This is supported by the finding of an increased risk of SCA in patients with low vitamin D levels; including those with both established cardiac disease (25, 27) and in those with non-ischemic cardiomyopathy (21), but also in an otherwise healthy population (23). Therefore, a comparison of the 25-OH-vitamin D levels between different OHCA categories of patients, with and without an acute coronary event, may be appropriate. Aims of the study In this study the investigators intend to give a thorough description of the study population based on demographic data, clinical information, medical history and biochemical parameters. The investigators plan to assess the total number of regional OHCA cases among patients reported to the ambulance service during the study period, and determine the proportion of cardiac subjects with documented VF. Next the clinical baseline profile of subjects included in the study will be compared to the total cardiac VF population. Hs-cTNT and BNP will be added to the baseline data for further classification of the included SCA patients. 1. The main aim of the study will be to evaluate the diagnostic value of copeptin in the setting of sudden cardiac arrest (SCA). 2. As a second aim the investigators intend to evaluate the association between VF and the content of EPA and DHA in red blood cells. 3. Furthermore, as vitamin D is associated with n-3 PUFAs in the diet, the third aim will be to assess the association between 25-hydroxy (OH)-vitamin D and VF. 4. Finally the investigators intend to analyse the survival rate in cardiac patients with OHCA and documented ventricular fibrillation.. Inclusion/exclusion/classification/controls Eligibility for this study is based on 1) age > 18 years, 2) SCD with VF, 3) signed informed consent from the patient (if conscious at admission) or by his/her family. Exclusion criteria consist of 1) SCD with primary asystole, 2) evidence of non-cardiac death (including cerebral haemorrhage/ infarction and pulmonary embolism) and 3) sudden death due to cardiac tamponade. All blood samples taken at inclusion will be immediately centrifuged and stored in aliquots at - 70 o C until the measurements can be performed. Laboratory technicians will be blinded with respect to clinical data. Patient groups will be defined according to: 1. SCA with MI 1. First MI 2. Recurrent MI 2. SCA without MI 1. No former heart disease 2. Known heart disease Copeptin, EPA/ DHA and vitamin D in the different clinical patient categories will be compared to controls collected from the RACS (Risk markers in the Acute Coronary Syndromes) database (NCT00521976). Statistical methods Statistical analysis will be performed using the statistical package SPSS (Statistical Package for the Social Sciences). A statistically significant level of p < 0.05 will be applied for all tests. Ethics and confidentiality The present study is conducted in accordance with the Helsinki Declaration of 1975 and later revisions and accepted by the Regional Board of Research Ethics as well as the Norwegian Health Authorities. Analytic data will be related to patient number and not to patient identity. According to Norwegian regulations, the family of non-survivors will be informed by the attending physician and the inclusion of patients needs to be documented in the hospital records. The family of the deceased is entitled to object to the use of any biological samples for research purposes. Patients regaining consciousness and mental capability during their hospital stay will be asked personally for a written informed consent. For the remaining survivors the next of kin will be asked for permission on behalf of the patient. If either the patient or the family refuses participation, blood samples already collected at resuscitation and admission will be destroyed.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Helse Stavanger HF.