Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 research and innovation programme to J.T.-H under acronym ESCAPE-NET Background Sudden cardiac arrest (SCA) is a major public health challenge and is associated with poor outcomes. Many drugs are known to increase risk of arrythmias and ultimately sudden cardiac death. To our knowledge an untargeted toxicological analysis has not previously been performed in an initially resuscitated SCA cohort. Purpose We aimed to determine the qualitative and quantitative drug composition present in SCA patients by using forensic toxicological analytical chemistry of all illicit, non-prescription and prescribed drugs, and further investigate whether these drugs are in therapeutic levels or overdosed and to correlate the clinical findings with the toxicology results. Methods We performed a prospective single-tertiary-center study and included all SCA victims (aged 18-90 years) admitted to our cardiac intensive care unit, between February 2019 to November 2019 (Figure 1). Traumatic and overt overdose related SCA were not included in the study. Drugs used during resuscitation and administered prior to sample collection were identified in each patient and excluded. Results We prospectively identified 85 all-cause SCA patients with a median age of 60 years (IQR: 53-71) and male predominance (80%). The majority had a shockable rhythm as first rhythm (95%). The major cause of cardiac arrest was acute and chronic ischemia (56/77, 66%), followed by cardiomyopathy (9/77, 12%), idiopathic ventricular fibrillation (8/77, 10%), bradycardia (2/77, 2.6%), primary arrhythmia (1/77, 1.3%), other (1/77, 1.3%). The remaining 8 patients (9.4%) died prior to diagnosis. A positive toxicology was identified in 67 patients (79%) with a total of 218 detected drugs. The most frequent drugs were mild analgesics (32/85, 38%), beta-blockers (21/85, 25%) and ACE-inhibitors/ARB (20/85, 24%). A total of 9 (11%) patients had one or more potentially abusable drugs detected, with the most common being opioid agonists in 5 patients (Figure 2). Importantly, all drugs were found at sub-therapeutic or therapeutic concentrations. None had overdose concentrations. Moreover, polypharmacy was common and a median of 2 drugs (IQR: 1-4) were detected (excluding caffeine that was detected in 83 patients). Conclusion We found that the majority had drugs detected, and polypharmacy is displayed in a considerable proportion. Potentially abusive drugs were encountered in 11%. However, we did not identify any occult overdose related cardiac arrests among all resuscitated SCA patients. In our setting, toxicological screening in cardiac arrest patients who is not obviously overdosed is excessive.
Introduction Prediction of ventricular arrhythmia recurrence in survivors of ventricular fibrillation out of hospital cardiac arrest (VF-OHCA) is important, but currently difficult. Risk of recurrence may be related to presence of myocardial scarring and dedicated late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) software allows for characterization of left ventricular scarring, including differentiation between core, border zone (BZ) and BZ channels that represent potential electrical circuits of slow conductivity responsible for ventricular arrhythmic events. Purpose Our study aims to characterize myocardial scarring as defined by LGE-CMR in survivors of a VF-OCHA and investigate its potential role for the risk of new ventricular arrhythmia. Methods Between 2018 and 2021, a total of 130 VF-OHCA patients had CMR, of which we included 28 patients with LGE-CMR before ICD implantation for secondary prevention. A total of 15 (54%) patients had signs of acute or chronic ischemic heart disease (IHD); and 13 (46%) patients had arrhythmogenic cardiomyopathy (ACM). Scar tissue including core, BZ and BZ channels were automatically detected by specialized investigational software. To differentiate BZ from healthy tissue and BZ from core, thresholds of 40% ± 5% and 60% ± 5% of the maximum signal intensity were applied. A BZ channel in the LGE-CMR reconstruction was defined as a continuous corridor of BZ between 2 core areas or between a core area and a valve annulus (Figure 1A+B). Results The median age was 56 years; 86% were men and the median left ventricular ejection fraction was 50±11%. A total of 16 (57%) patients had an inferior scar on LGE-CMR, and 8 (29%) patients with IHD were incompletely revascularized. After a median follow-up of 98 days, 9 (32%) patients (6/9 with IHD, including 5/6 incompletely revascularized; 3/9 with ACM) had recurrence of ventricular arrhythmia (6/9 monomorphic ventricular tachycardia (VT)). A significantly higher number of patients with BZ channels had recurrence of ventricular arrhythmia compared with patients without BZ channels (7/11 vs. 2/17; P=0.01) (Figure 2). The number of BZ channels (3±1 vs. 2±1; P=0.13); scar mass (21±8g vs. 14±11g; P=0.21); core mass (7±4g vs. 4±5g; P=0.14); and BZ mass (11±5g vs. 9±7g; P=0.42) were insignificantly higher in patients with recurrent ventricular arrhythmia compared with patients without. Conclusion Borderzone channels analyzed by LGE-CMR were associated with subsequent recurrence of ventricular arrhythmia in patients with out of hospital cardiac arrest caused by ventricular fibrillation. Funding Acknowledgement Type of funding sources: None.
Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 research and innovation programme under acronym ESCAPE-NET, registered under grant agreement No 733381 Introduction Sudden cardiac death (SCD) remains a major public health issue. Most cases in the general population are caused by ischemic heart disease, and often occur in patients without known ischemic heart disease. The assessment of risk factors may point to novel causal pathways or new targets for intervention and risk prediction of SCD. Objective The aim of this study was to evaluate the effect of family history of sudden death, prior history of atrial fibrillation (AF), and anterior infarct location on ECG on the development of ventricular fibrillation (VF) during first ST-elevation myocardial infarction (STEMI). Methods We performed individual participant data meta-analyses of three European case-control studies including first STEMI patients (aged 18-80 years) with VF (cases) and without VF (controls) before revascularization (GEVAMI, AGNES, and PREDESTINATION). Analyses were done using fixed-effect, inverse variance weighted meta-analysis and multivariable logistic regression. Potential confounding variables were identified using causal diagrams and missing data were handled with multiple imputation for each cohort separately. Results We included 1664 cases and 2497 controls (median age (IQR) = 59 (51-67) years, 20% females) in the analyses. After adjusting for potential confounding, we found an independent and additive association between the three exposures and VF (see picture): for family history of sudden death odds ratio (OR) 1.59 (95% confidence interval: 1.37-1.85), for AF OR 2.41 (1.49-3.89), and for anterior myocardial infarction OR 1.50 (1.32-1.71). Further investigation indicated increased effect of family history with multiple sudden deaths in the family, a stronger effect of AF on VF developing within the first minutes of symptoms, and the effect of anterior infarctions being modified by enzymatically determined infarct size. The three risk factors showed an additive effect: with one factor present OR 1.59 (1.38-1.84), two factors OR 2.41 (1.95-2.99), and all three factors OR 5.49 (1.43-21.1). Complete case analysis gave similar results for all analyses. Conclusions Family history of sudden death, history of AF, and anterior infarct location with significant interaction with enzymatic infarct size were all independently and additively associated with an increased risk of VF in patients with a first STEMI.
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