ObjectivePresentations of non-cardiac chest pain (NCCP) to the emergency department (ED) are increasing. More knowledge of prognosis and healthcare utilisation of patients with NCCP is necessary to optimise their management.MethodsThis study is a prospective, observational, prevalence-based cohort study conducted from September 2015 to February 2016 with 1-year follow-up including all patients 18 years and older referred to the ED with chest pain. Discharge diagnoses, mortality, major adverse cardiac events (MACE), re-presentations to the ED, hospitalisations, cardiac interventions and outpatient monitoring were assessed.ResultsMore than 60% of the 1239 patients presenting with chest pain were discharged with NCCP. The all-cause 1-year mortality rate of patients with NCCP was 2.3% compared with 7.2% in patients with cardiac chest pain (CCP) (p<0.001) and the occurrence of MACE was 5.1% vs 8.3%, respectively (p=0.026). Previous history of coronary artery disease (CAD) in patients with NCCP was identified as a predictive factor for MACE (OR 4.30 (95% CI 1.24 to 14.89), p=0.021). Patients with NCCP had more non-invasive interventions than patients with CCP (proportion of 0.225 vs 0.165 per patient, p<0.001) and 13.7% of patients with NCCP re-presented at the ED within 1  year.ConclusionThe majority of patients referred to the ED with chest pain are discharged with NCCP. The prognosis of patients with NCCP is better than patients with CCP; however, they are at risk for MACE due to a history of CAD. Patients with NCCP moreover use a substantial amount of medical resources, stressing the importance of good triage to minimise unnecessary healthcare utilisation while still preventing MACE.

Ventricular arrhythmias, consisting of single ectopic beats (sEB), multiple EB (mEB), and Torsades de Pointes (TdP, defined as >5 beats with QRS vector twisting around isoelectric line) can be induced in the anesthetized chronic AV-block (CAVB) dog by dofetilide (IKr-blocker). The interplay between temporal dispersion of repolarization, quantified as short-term variability (STV), and spatial dispersion of repolarization (SDR) in the initiation and perpetuation of these arrhythmias remains unclear. Five inducible (>3 TdPs/10') CAVB dogs were observed for 10' from the start of dofetilide infusion (0.025mg/kg, 5'). An intracardiac decapolar electrogram (EGM) catheter and 30 intramural cardiac needles in the left ventricle (LV) were introduced. STVARI was derived from 31 consecutive activation recovery intervals (ARI) on the intracardiac EGM, using the formula: . The mean SDR3D in the LV was determined as the three-dimensional repolarization time differences between the intramural cardiac needles. Moments of measurement included baseline (BL) and after dofetilide infusion prior to first 1) sEB (occurrence at 100±35"), 2) mEB (224±96"), and 3) non self-terminating TdP (454±298"). STVARI increased from 2.15±0.32ms at BL to 3.73±0.99ms* prior to the first sEB and remained increased without further significant progression to mEB (4.41±0.45ms*) and TdP (5.07±0.84ms*) (*p<0.05 compared to BL). SDR3D did not change from 31±11ms at BL to 43±13ms prior to sEB, but increased significantly prior to mEB (68±7ms*) and to TdP (86±9ms*+) (+p<0.05 compared to sEB). An increase in STV contributes to the initiation of sEB whereas an increase in SDR is important for the perpetuation of non self-terminating TdPs.

Ventricular remodelling can make the heart more susceptible to ventricular arrhythmias like torsades de pointes. Understanding the underlying mechanisms of initiation of ventricular arrhythmias and the determining factors for its severity has the potential to uncover new interventions. Beat-to-beat variation of repolarisation, quantified as short-term variability of repolarisation (STV), has been identified as an important factor contributing to arrhythmogenesis. This article provides an overview of experimental data about STV in relation to the initiation of torsades de pointes in a canine model of complete chronic atrioventricular block susceptible to torsades de pointes arrhythmias. Furthermore, it explores STV in relation to the severity of the arrhythmic outcome.

BACKGROUND The anesthetized, complete chronic atrioventricular block (CAVB) dog model allows reproducible inducibility of torsades de pointes (TdP) arrhythmias due to ventricular remodeling and after a challenge with an I Kr blocker. High-rate pacing (HRP) prevents ventricular arrhythmias but has long-term detrimental effects on cardiac function when applied continuously. Temporal dispersion of repolarization, quantified as short-term variability (STV), increases before ventricular arrhythmias and has been proposed as a marker to guide HRP.OBJECTIVE The purpose of this proof-of-principle study was to show that automatically determined STV can guide HRP to prevent imminent ventricular arrhythmias.METHODS Eight CAVB dogs were implanted with an implantable cardioverter-defibrillator (ICD) with software to automatically determine STV (STV ICD ) in real time. During HRP, STV was measured offline from right ventricular (RV) electrograms (EGMs) and left ventricular (LV) monophasic action potential durations (MAPDs) (STV RV,EGM/LV,MAPD ). The CAVB dogs were challenged twice with dofetilide (0.025 mg/kg intravenously over 5 minutes or until the first TdP). In experiment 1, the individual STV ICD threshold before the first arrhythmic event was determined and programmed into the ICD. In experiment 2, HRP with 100 bpm was initiated automatically once the STV ICD threshold was reached. RESULTSIn experiment 1, 8 of 8 dogs had repetitive TdP, and STV ICD increased from 0.96 6 0.42 ms to 2.10 6 1.26 ms (P ,.05). In experiment 2, all dogs reached the STV threshold. HRP decreased STV RV,EGM/LV,MAPD from 2.02 6 1.12 ms to 0.78 6 0.28 ms, which was accompanied by prevention of TdP in 7 of 8 dogs.CONCLUSION STV can guide HRP automatically by an ICD to prevent ventricular arrhythmias.

Background Short‐term variability of the QT interval (STV QT ) has been proposed as a novel electrophysiological marker for the prediction of imminent ventricular arrhythmias in animal models. Our aim is to study whether STV QT can predict imminent ventricular arrhythmias in patients. Methods and Results In 2331 patients with primary prophylactic implantable cardioverter defibrillators, 24‐hour ECG Holter recordings were obtained as part of the EU‐CERT‐ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators) study. ECG Holter recordings showing ventricular arrhythmias of >4 consecutive complexes were selected for the arrhythmic groups (n=170), whereas a control group was randomly selected from the remaining Holter recordings (n=37). STV QT was determined from 31 beats with fiducial segment averaging and calculated as , where D n represents the QT interval. STV QT was determined before the ventricular arrhythmia or 8:00  am in the control group and between 1:30 and 4:30  am as baseline. STV QT at baseline was 0.84±0.47 ms and increased to 1.18±0.74 ms ( P <0.05) before the ventricular arrhythmia, whereas the STV QT in the control group remained unchanged. The arrhythmic patients were divided into three groups based on the severity of the arrhythmia: (1) nonsustained ventricular arrhythmia (n=32), (2) nonsustained ventricular tachycardia (n=134), (3) sustained ventricular tachycardia (n=4). STV QT increased before nonsustained ventricular arrhythmia, nonsustained ventricular tachycardia, and sustained ventricular tachycardia from 0.80±0.43 ms to 1.18±0.78 ms ( P <0.05), from 0.90±0.49 ms to 1.14±0.70 ms ( P <0.05), and from 1.05±0.22 ms to 2.33±1.25 ms ( P <0.05). This rise in STV QT was significantly higher in sustained ventricular tachycardia compared with nonsustained ventricular arrhythmia (+1.28±1.05 ms versus +0.24±0.57 ms [ P <0.05]) and compared with nonsustained ventricular arrhythmia (+0.34±0.87 ms [ P <0.05]). Conclusions STV QT increases before imminent ventricular arrhythmias in patients, and the extent of the increase is associated with the severity of the ventricular arrhythmia.

Background: Short-term variability (STV) of repolarization of the monophasic action potential duration (MAPD) or activation recovery interval (ARI) on the intracardiac electrogram (EGM) increases abruptly prior to the occurrence of ventricular arrhythmias in the chronic AV-block (CAVB) dog model. Therefore, this parameter might be suitable for continuous monitoring of imminent arrhythmias using the EGM stored on an implanted device. However, 24/7 monitoring would require automatic STV ARI measurement by the device. Objective: To evaluate a newly developed automatic measurement of STV ARI for prediction of dofetilide-induced torsade de pointes (TdP) arrhythmias in the CAVB-dog. Methods: Two retrospective analyses were done on data from recently performed dog experiments. (1) In seven anesthetized CAVB-dogs, the new automatic STV ARI method was compared with the gold standard STV MAPD at baseline and after dofetilide administration (0.025 mg/kg in 5 min). (2) The predictive value of the automatic method was compared to currently used STV ARI methods, i.e., slope method and fiducial segment averaging (FSA) method, in 11 inducible (≥3 TdP arrhythmias) and 10 non-inducible CAVB-dogs. Results: (1) The automatic measurement of STV ARI had good correlation with STV MAPD (r 2 = 0.89; p < 0.001). Bland-Altman analysis showed a small bias of 0.06 ms with limits of agreement between −0.63 and 0.76 ms. (2) STV ARI of all three methods was significantly different between inducible and non-inducible dogs after dofetilide. The automatic method showed the highest predictive performance with an area under the ROC-curve of 0.93, compared to 0.85 and 0.87 of the slope and FSA methods, respectively. With a threshold of STV set at 1.69 ms, STV ARI measured with the automatic method had a sensitivity of 0.91 and specificity of 0.90 in differentiating inducible from non-inducible subjects. Smoczyńska et al.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation Background  An increase in temporal dispersion of repolarization, quantified as short-term variability of the QT-interval (STV-QT), precedes ventricular arrhythmias and has therefore been proposed as a marker for monitoring of imminent arrhythmic risk. A reversal of an increased STV by high rate pacing at 100 bpm was anti-arrhythmic in the chronic atrioventricular block dog model susceptible to Torsade de Pointes arrhythmias upon challenge with an IKr-blocker. The objective of the current study was to investigate the physiological modulation of STV by pacing in patients with an indication for an implantable cardioverter defibrillator (ICD), and to compare atrial and ventricular pacing. Methods  ECG recordings were obtained with a sampling frequency of 1200 Hz in 10 dual chamber ICD patients and 10 patients with cardiac resynchronization therapy with defibrillation function (CRT-D) during the implantation or replacement. One-minute recordings were made during sinus rhythm (SR), and during pacing at 80 and 100 beats per minute (bpm) from the atrium (AAI), atrium and right ventricle (DDD RVp), and during atrio-biventricular pacing (DDD BiVp). The QT-interval was determined offline with fiducial segment averaging at one minute of each pacing rate, and 31 consecutive beats were used to calculate STV-QT with the following formula: ∑|D(n + 1)-Dn |/(N×√2), where D represents the determinant of repolarization (in this case the QT interval), and N represents the number of beats taken into account minus 1. Results  In the patients overall, STV-QT decreased from 1.27 ± 0.38 ms in SR (±58 bpm) to 0.86 ± 0.26 ms* during AAI80, and to 0.68 ± 0.22 ms*† during AAI100 (*p &lt; 0.05 compared to SR, †p &lt; 0.05 compared to 80 bpm). The same decrease was seen during DDD80 RVp (0.81 ± 0.28 ms*) and during DDD100 RVp (0.66 ± 0.22 ms*†) (fig. 1). Additionally, DDD BiVp decreased STV-QT to 0.78 ± 0.20 ms* at 80 bpm and to 0.62 ± 0.19 ms* at 100 bpm in CRT-D patients (fig. 2). Conclusion  Pacing at 80 and 100 bpm decreases STV-QT compared to sinus rhythm both in dual chamber ICD patients and CRT-D patients. The modulation of STV-QT is similar during atrial, and atrio- right ventricular and atrio-biventricular pacing. Abstract Figure. Modulation of STV-QT by AAI and DDD RVp

Background The anesthetized, chronic complete atrioventricular block (CAVB) dog model allows reproducible inducibility of Torsade de Pointes (TdP) arrhythmias due to ventricular remodeling and after a challenge with an IKr-blocker. High rate pacing (HRP) prevents ventricular arrhythmias, but has long-term detrimental effects on cardiac function when applied continuously. Temporal dispersion of repolarization, quantified as short-term variability (STV), increases prior to ventricular arrhythmias and has been proposed as a marker to guide HRP. Purpose A proof-of-principle study to show STV determined automatically and in real-time by an ICD can guide HRP to prevent imminent ventricular arrhythmias. Methods Eight CAVB dogs were implanted with an ICD (Medtronic, lead in the right ventricular (RV) apex), with software to automatically determine STV online (STV-ICD). STV was determined from the activation recovery interval (ARI) of 31 consecutive beats with the formula: STV = Σ|ARI(n+1) − ARI(n)|/(N*√2). The CAVB dogs were challenged twice with dofetilide (0.025 mg/kg i.v. in 5 minutes or until the first TdP). In the first experiment, the individual STV-ICD threshold was determined prior to the first arrhythmic event and programmed into the ICD. In a serial experiment, HRP was initiated automatically once the STV-ICD threshold was reached, by gradually increasing the heart rate to 100 bpm. Occurrence of TdPs was monitored for 10 minutes from the start of dofetilide infusion in both experiments. During HRP, STV was measured offline from RV electrograms (EGM) and left ventricular (LV) monophasic action potential durations (MAPD) (STV-offline). Results During the inducibility experiment, 8/8 dogs had repetitive TdPs and STV-ICD increased from 0.96±0.42 to 2.10±1.26 ms* (*p&lt;0.05). During the prevention experiment, all dogs reached the STV threshold. HRP decreased STV-offline from 2.02±1.12 to 0.78±0.28 ms*, which was accompanied by prevention of TdPs in 7/8 dogs* (Figure 1). Conclusion Temporal dispersion of repolarization, quantified as STV, can guide HRP automatically by an ICD to prevent ventricular arrhythmias. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation Public Private Partnership