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. 2016 Feb 22;17(Suppl 5):v3–v5. doi: 10.1093/europace/euv325

Allied Professionals

PMCID: PMC4892104
Europace. 2016 Feb 22;17(Suppl 5):v3–v5.

7: Screening for eligibility for subcutaneous icd implant in adults with congenital heart disease: how many patients are eligible?

S Cunningham 1, NL Walker 2, GA Wright 2, J Goodwin 1, J Reilly 1, DT Connelly 2

Abstract

The subcutaneous implantable cardioverter-defibrillator (S-ICD) is a recent advance in ICD technology, and has been available for 5 years. Many centres are using these devices in young patients and in patients with abnormal anatomy which might preclude the insertion of transvenous ICDs. However, in order to be eligible for S-ICD implantation, patients need to have an appropriate ratio of QRS amplitude to T wave amplitude in at least two of the three vectors through which the device can sense and analyse the ECG. Previous studies have suggested that 80-90% of ICD recipients might be eligible for S-ICD on the basis of their ECG vectors, but previous studies have included very few patients with congenital heart disease. We studied ECG vectors in 31 adult patients (15 male; age 36.5 + 14.5 years) with congenital heart disease (ACHD). All were attending the Scottish Adult Congenital Cardiac Service clinic at our institution. Three patients had tetralogy of Fallot, 10 had aortic disease, 7 had transposition of the great arteries, 4 had valvular disease, 5 had septal defects, 1 had Ebstein's anomaly and one had complex disease. Twenty eight patients had had prior corrective or palliative surgery. ECGs were recorded according to the vectors recommended by the S-ICD manufacturer, with patients in the supine, erect, right lateral and left lateral positions. ECGs were analysed manually using the manufacturer's ECG screening tool. Sixteen patients (51.6%) had ECGs that would render them “eligible” for S-ICD, and fifteen were “ineligible” (48.4%). Ineligible patients were more likely to have abnormal T wave morphology (p = 0.001), prolonged QRS duration (p = 0.01) or prolonged QT interval (p = 0.05). Prior cardiac surgery, age, sex, height and weight were not predictors of eligibility. Conclusion: in this small study, a high proportion of ACHD patients would be considered ineligible for S-ICD implantation, based on ECG abnormalities which might make them liable to T wave oversensing with a concomitant risk of inappropriate shocks. Further refinement of the QRS and T wave sensing algorithms in these devices might be useful in improving the eligibility for S-ICD in ACHD patients.

Europace. 2016 Feb 22;17(Suppl 5):v3–v5.

8: Identifying the outcome of patients in a multispeciality nurse led rapid access blackout clinic undergoing implantable loop recorders for unexplained syncope

A Hall 1, PJ Mudd 1, C Wilson 1, AF Rice 1, A Iglesias 1, S Taggart 1, S James 1, AR Thornley 1, AJ Turley 1, NJ Linker 1

Abstract

Introduction: Following the 2009 ESC Guidelines for the diagnosis and management of syncope a multi-speciality nurse led rapid access blackout service was developed. Investigation of syncope includes prolonged monitoring in the form of implantable loop recorders (ILR) in patients with recurrent syncope of uncertain origin and absence of high risk criteria. Our aim was to ensure compliance with ESC recommendations and identify the diagnostic yield from ILR use.

Methods: 1783 patients attended the clinic (Dec 2010–Oct 2014) of which 90 (5%) underwent ILR implant (43 male, median (range) age 62yrs, (23–88yrs). Information was obtained from medical records to identify history of syncope, episodes, diagnosis from ILR interrogation and outcome.

Results: 97% (87) compliance with ESC recommendations. 3% (3) experienced 1 episode of syncope resulting in 2 RTA's/1 traumatic injury and therefore ILR considered clinically appropriate. 34.5% (31) had symptoms post ILR implant. Diagnosis in 11.1% (10) was sinus node disease (7), 2nd degree AVB (1), AF with slow ventricular response (1) all resulting in pacemaker implant (9). VT (1) resulting in ICD implant (1). 23.4% (21) had symptoms related to normal sinus rhythm or had failed to activate their device. 65.5% (59) patients had no symptoms following ILR. These patients had significantly more symptoms (13.8 average episodes) prior to the ILR implant than patients who were diagnosed with an arrhythmia (4.0) or who were in sinus rhythm (10.6) at the time of subsequent syncope.

Conclusion: Findings are comparable with other studies and demonstrate a multispecialty nurse led service is equivalent to a traditional medical model. ILR is a valuable tool in the diagnosis of syncope. 34.5% (31) had symptom correlations and subsequent diagnosis. 65.5% (59) experienced no further syncope. There was no difference in mean duration of symptoms prior to ILR but the most symptomatic patients had less recurrences.

Europace. 2016 Feb 22;17(Suppl 5):v3–v5.

9: Implant of medtronic linq in an outpatient setting

AJ Jackson 1, T Rashid-Fadel 1, RC Bond 1, J Rosengarten 1, G Thomas 1

Abstract

Introduction: Implantable loop recorders (ILRs) are an important diagnostic tool for patients with infrequent palpitations/symptoms. In our institution ILRs are implanted in a cardiac laboratory under aseptic conditions by a physician supported by a physiologist and nurse. The new injectable Medtronic reveal LINQ is 87% smaller than previous ILRs and implanted using a pre-loaded insertion tool. We produced a standard operating procedure for the implantation of injectable ILRs in an outpatient setting.

Methods: All ILRs were implanted by a physician supported by a physiologist. The consultation room was clean to a standard accepted by infection control. Patients were seated on a reclining chair/couch that lies fully flat (in case of vagal episode). Baseline pulse and blood pressure recordings were taken. Sterile gloves and gown were worn. The left side of the chest was cleaned with chlorhexidine and draped with a sterile drape. Local anaesthetic was infiltrated and the device implanted using the Medtronic pre-loaded device. Steri-strips or a single suture were used to close skin. Post procedure the patient was given remote monitoring equipment and explained how to perform a download onto Carelink. The patient was allowed to sit in waiting area of cardiology outpatients for a minimum of 20 minutes to allow for recovery. A patient questionnaire was performed whilst recovering.

Results: 22 Medtronic LINQ devices were implanted and results compared with implanted reveal XT devices over a comparable time period. The mean age was 50.4 ± 3.9 years old for LINQ devices and 57.3 ± 4.9 for reveal XT devices. R waves at implant were 0.7 ± 0.1 for LINQ devices and 0.4 ± 0.1 for reveal XT devices (p = ns). No devices were repositioned. No infections were reported after 12 months follow up. In LINQ devices a diagnosis was made in 10 patients (45%) 39.2 ± 15.7 days after implant. 5 patients had pauses requiring permanent pacemaker implantation and 5 had paroxysmal AF. The time to diagnosis from implant in reveal XT devices was longer (110.7 ± 35.3 days; n = 9, p = ns) 62% of patients found the procedure less painful than expected whilst 38% reported the pain from the procedure as expected. 81% of patients were very comfortable in an outpatient setting and 19% were comfortable. 79% of patients felt that the time they waited post procedure was just right, 14% thought it was too long and 7% thought it was unnecessary. The increased cost of the LINQ device compared to the reveal XT ILR is offset by performing the procedure in an outpatient environment instead of a catheter laboratory. Less staff are required for the procedure and the cost of consumables is lower than performing the procedure in the catheter laboratory as no pack is required. The time in the catheter laboratory can be used for more appropriate and profitable procedures.

Conclusions: Injectable ILRs can be implanted safely in an outpatient setting with no reported device infections. The time to diagnosis is less than with reveal XT ILRs but this did not reach significance in this study however robust remote follow up protocols ensure that any significant event on a LINQ device is picked up within a maximum of forty-eight hours (over a weekend period). Implantation of injectable ILRs gives a good patient experience. The opportunity in the future for physiologist led implants may be easier with this minimally invasive procedure, relieving physicians from the need to perform this procedure and expanding the role of the cardiac physiologist.

Europace. 2016 Feb 22;17(Suppl 5):v3–v5.

10: Does time from diagnosis of atrial fibrillation to ablation effect success of catheter ablation?

LJS Jarrett-Smith 1, CB Butcher 1, DL Lysitsas 1, TW Wong 1, VM Markides 1, DGJ Jones 1, WH Hussain 1

Abstract

Introduction: Catheter ablation (CA) is an effective treatment for drug refractory symptomatic paroxysmal (PAF) and persistent (PeAF) atrial fibrillation (AF). Lower CA success rates for PeAF are well documented due to multiple factors, however there are limited data on the influence of length of AF history upon CA success.

Methodology: All patients undergoing first time CA for drug refractory symptomatic atrial fibrillation (AF) from 2007 to 2011 were retrospectively reviewed. PAF (recurrent AF spontaneously terminating <7 days) and PeAF (continuous AF >7 days), and duration of AF history (time since first ever AF documentation) until CA, were assessed blinded to the result of CA. Recurrence was defined as >30 seconds of AF (assessed by repeated 3-7 day ambulatory monitoring and documentation of AF by ECG or typical symptom recurrence) >3 months after index CA and freedom from AF analysed at 1 year (single procedure success).

Results: In total, 370 patients (172 peAF, 198 PAF) were identified. PeAF and PAF groups were matched by age (60.6 ± 10.3 years), gender (male 61%), diabetes (7.8%), AF duration (53.69± 54.82 months) and EF < 35% (20%). There was a trend towards greater CHADS2 score (p = 0.055), and significantly more patients with LA dilatation (>4cm; 123(72%) vs 100(51%), p < 0.0001) in the PeAF group. Post CA, single procedure success was 68% for PAF and 59% for PeAF patients (p = 0.07). Multivariate analysis (including diabetes, CHADS2 score, age, ejection fraction (EF) <35%, and LA > 4cm) found that duration of AF to be an independent predictor of CA success in both groups (p = 0.017 for PAF and 0.019 for PeAF); interestingly, EF <35% was an additional independent predictor of success in the PeAF group (p < 0.01).

Conclusions: Patients with AF, whether paroxysmal or persistent, appear to benefit from early CA regardless of underlying risk factors. Early referral to specialist arrhythmia services may improve likelihood of procedural success. Low EF does not preclude a successful result from CA.

Europace. 2016 Feb 22;17(Suppl 5):v3–v5.

11: Detection and management of atrial fibrillation in the pacing clinic

PA Rees 1, MA Gilmore 1, J Barry 1

Abstract

Introduction: Atrial Fibrillation (AF) is a common arrhythmia with increasing prevalence. It is a significant risk factor for ischaemic stroke. Oral anticoagulants are effective treatments which substantially lower the risk of stroke in patients with AF. The decision to utilise these treatments is based on an assessment of a patient's stroke risk (assessed using the CHADS2VASC score) vs their potential bleeding risk on anticoagulation (assessed using the HASBLED score).

Modern pacemakers are capable of acting as cardiac monitors and store information pertaining to arrhythmias. In particular AF may be noted at time of follow up. Alternatively, if EGM storage has not been previously activated, atrial arrythmias may be suggested by the fact that a device has mode switched.

We sought to investigate the frequency of AF in our bradycardia device population and to determine whether appropriate action had been taken on noting AF or upon it being suggested by mode switch episodes.

Methods: A retrospective analysis of pacing clinic notes was made for 100 consecutive patients attending for bradycardia device interrogation . In particular, data pertaining to whether the patient was known to have AF was recorded, as was the presenting rhythm at interrogation, whether stored EGMs documented AF and whether mode switching information was recorded. We recorded what action had been taken and whether a doctor had been informed in the case of newly diagnosed AF.

Results: 32 of the 100 patients were known to have AF.

Of the 68 patients not known to have AF, 8 patients were in AF at time of interrogation and 4 had episodes of AF stored on EGM.

17 patients were in sinus rhythm but had documentation of mode switch episodes of greater than 30 seconds duration. 11 patients were in sinus rhythm with mode switch episodes of a maximum duration less than 30 seconds. 28 patients were in sinus rhythm with no suggestion of atrial arrythmias.

Of the 12 patients who had newly diagnosed AF, there was clear documentation in 9 cases that their GP or physician had been informed. A further 1 case of the 12 was already anticoagulated but for an alternate indication. In the case of 2 patients there was no clear documentation that action had been taken.

Of the 17 patients with mode switch episodes lasting greater than 30 seconds, 10 had EGM monitoring activated on their devices and a plan was instituted for follow up after a suitable time interval. 1 patient with an older device not capable of EGM monitoring was offered Holter monitoring. For 6 patients with mode switch episodes no clear plan of action was documented.

Conclusions: AF is highly prevalent in our pacemaker population; routine pacemaker interrogation often highlights a change in AF status.

Physiologists frequently act appropriately upon discovering AF; this needs to be documented consistently and communicated effectively with patients and allied professionals involved in their care.

Europace. 2016 Feb 22;17(Suppl 5):v3–v5.

12: The efficacy of a nurse-led cardioversion service on clinical outcomes

C Brennan 1, NT Srinivasan 1, KH Patel 1, MD Lowe 1, OR Segal 1

Abstract

Introduction: Considerable heterogeneity exists in the shock therapy delivered during direct current cardioversion (DCCV) for arrhythmia in clinical practice. European guidelines recommend an initial synchronised shock of 120-150J for atrial fibrillation (AF) but variability in practice exists. In our center we introduced a nurse led cardioversion service in April 2014 using a standard 200J shock with a maximum of 3 shocks. We then assessed the clinical outcomes of DCCV on patient outcome and patient experience.

Methods: Retrospective demographic, echocardiographic, ECG and DCCV data were collected from April to September 2013 and the same period in 2014 to enable a direct comparison of compliance with European Resuscitation Council and the Heart Hospital guidelines and evaluate any differences in clinical outcomes. Successful DCCV was defined as sinus rhythm on discharge.

Results: 47 and 36 patients underwent DCCV between April and September in 2013 and 2014, respectively. Pre-April 2014, 61% and 16% of DCCV were compliant with national and local guidelines for AF DCCV respectively, resulting in 89% and 100% success rates. Similarly, post-April 2014 3% and 97% of DCCV were compliant with national and local guidelines respectively, resulting in 100% and 97% success rates. Following introduction of the nurse-led service with 200J fixed shock protocol, successful DCCV rates increased from 80% to 92% (Fig. 1). Follow-up waiting times pre-and post-April 2014 were 65 + /−52 days and 48 + /−26 days, respectively.

Conclusion: Specialist-nurse led DCCV ensures a more consistent service and arguably better clinical outcomes with potential for a shorter follow-up waiting time.

graphic file with name euv32501.jpg

Figure 1 Improved outcome to Sinus Rhythm at discharge with the introduction of a nurse led cardioversion service in April 2014.

Europace. 2016 Feb 22;17(Suppl 5):v3–v5.

13: Do major ion channels of pacemaker clock also play a role in atrioventricular nodal conduction in young and aged rats?

Y Saeed 1, I Temple 2, Z Borbas 2, A Atkinson 2, J Yanni 2, J Yanni 2, M Boyett 2, C Garratt 1, H Dobrzynski 2

Abstract

Introduction: Cellular mechanisms that influence atrioventricular (AV) nodal conduction are complex. Multiple studies have been performed to explain such mechanisms but none can fully explain the "riddle" of the AV node. The role of pacemaking channels on the AV nodal conduction has not been previously studied. Also with ageing there is an increase in the incidence of AV nodal dysfunction leading to AV block. We have studied the role of pacemaking ion channels and gap junctions on the AV nodal conduction with ageing.

Methods: Electrophysiological (EP) and immunohistochemistry experiments are performed on male rats aged 3 months (equivalent to 20 year old humans; n = 24) and 2 years (equivalent to 70 year old humans; n = 15). In the electrophysiology experiments, Atrio-hisian (AH) interval, Wenkebach cycle length (WCL) and AV node effective refractory period (AVNERP) was measured. We have used caesium (Cs+) (2 mM) to block HCN channels responsible for the funny current (If), and ryanodine (2 µM) to block RyR2 channels responsible for Ca2+ release from the sarcoplasmic reticulum in the two age groups. Protein expression was studied using immunofluorescence and confocal microscopy on sections from each group (from n = 8 young and n = 9 old rats) from different regions of the AV conduction axis: inferior nodal extension (INE), compact node (CN) and penetrating bundle (PB). We used the t-test for statistical analysis.

Results: Without drugs to block the HCN and RyR2 channels, there was a significant prolongation of the AH interval (P < 0.005), WCL (P < 0.005) and AVNERP (P < 0.001) with ageing. In young rats (but not old rats), Cs+ prolonged the AH interval (P < 0.001), WCL (P < 0.01) and AVNERP (P < 0.01). Ryanodine prolonged the AH interval (P < 0.01) and WCL (P < 0.01) in young and old rats. Immunofluorescence revealed that with ageing: Cx43 (a gap junctional protein) is downregulated in the PB (P < 0.05); Cx40 (another gap junctional protein) is upregulated in the INE and CN (P < 0.05); In terms of calcium handling proteins: RyR2 is downregulated in the CN and PB (P < 0.05); SERCA2a is upregulated in the PB (P < 0.05). A trend of down regulation was observed in HCN4 expression in the PB (P = 0.051).

Conclusion: For the first time, we have shown that both HCN and RyR2 channels play a role in AV nodal conduction. With ageing the effect of If-current in the AV nodal conduction decreases. The change in RyR2 and SERCA2a reduces the cytosolic calcium concentration in the AV node with ageing. Both these effects are likely to decrease conduction across the AV node with ageing that can results in higher incidence of AV block.

Europace. 2016 Feb 22;17(Suppl 5):v3–v5.

14: Anatomical and functional determinants of preferential rotor locations and stability in atrial fibrillation

FS Ng 1, CH Roney 1, MT Debney 1, C Eichhorn 1, A Nachiappan 1, NA Qureshi 1, RA Chowdhury 1, P Kanagaratnam 1, AR Lyon 1, NS Peters 1

Abstract

Introduction: Rotors have been shown to drive atrial fibrillation (AF) and targeting these sites has emerged as an ablation strategy. However, factors that influence the locations and stability of rotors and spiral waves in AF remain unclear and have mainly be studied in silico or in cell monolayers, which lack the anatomical and structural complexities of real atria. We experimentally assessed the relative importance of various anatomical, structural and functional factors in determining rotor locations in the left atrium.

Methods: Isolated, perfused canine left atrial preparations (n = 6) were optically mapped at baseline and after AF induction with pacing and acetylcholine. Rotor core locations were tracked using a novel computational algorithm for 80s of AF. The left atria were then divided into 9 regions for Cx43 immunohistochemistry and fibrosis analysis. Conduction and repolarization data from optical mapping, and Cx43 and fibrosis data were compared between regions with high and low rotor densities to assess for determinants of rotor locations.

Results: Rotors in AF locate preferentially to specific regions of the left atrium (Figure), though their distributions vary between hearts. Areas of high rotor densities are often closely associated with pulmonary vein (PV) ostia. There were no differences between Cx43 and fibrosis quantity/distribution between areas of high and low rotor density. There were slower AP upstrokes (p < 0.05) and trends towards shorter APDs (APD75 at 300ms: 41 ± 8ms vs. 63 ± 12ms, p = 0.1) in areas with high incidences of rotors.

Conclusions: There are preferential locations for AF rotors in the left atrium. Anatomical (locations of PVs) and functional factors (spatial heterogeneities of repolarization and conduction) are more important in determining rotor sites than structural factors such as regions of fibrosis. Identification of the determinants of preferential rotor sites can help optimize ablative therapy for AF.

graphic file with name euv32502.jpg

Europace. 2016 Feb 22;17(Suppl 5):v3–v5.

15: Pacemaker-induced cardiomyopathy in the sheep: rva but not rvot pacing results in a heart failure cellular phenotype

GJ Kirkwood 1, M Lawless 1, C Pearman 1, E Radcliffe 1, J Caldwell 1, AW Trafford 1

Abstract

Introduction: RV pacing can have adverse effects on LV function and approximately 10% of patients develop Pacemaker-induced Cardiomyopathy (PiCM). The pathophysiology of this is poorly understood, although previous models have shown that dyssynchronous ventricular activation can cause abnormal calcium handling and apoptosis. As yet, no studies have determined whether physiological-rate RVA pacing results in a cellular heart failure phenotype and whether this can be prevented by pacing from the RV outflow tract (RVOT).

Methods: Female Welsh mountain sheep were implanted with dual chamber pacemakers. Ventricular leads were positioned either in the RV apex or RV outflow tract, and VDD mode pacing with a short AV delay was performed for 3 months. ECG studies were performed at baseline and end point to assess heart rate variability and autonomic function (2 stage pharmacological block technique). After death, cardiomyocytes isolated from the LV free wall were studied using patch clamp techniques. Results were compared with uninstrumented control animals and with a model of heart failure induced via rapid ventricular pacing (VVI 210 bpm for 4–6 weeks).

Results: VDD mode pacing from either the RVA or RVOT did not result in clinical or echocardiographic features of heart failure and there was no evidence of autonomic dysfunction. However, cardiomyocytes from RVA-paced animals demonstrated profound abnormalities of cellular calcium handling. Peak systolic calcium and the calcium transient magnitude were attenuated to a similar degree as was seen in heart failure. RVOT pacing resulted in an intermediate phenotype with less pronounced changes. Preliminary results from confocal microscopy suggest that RVA pacing resulted in a depletion of transverse tubules (T-tubules) comparable to that seen in heart failure.

Conclusion: RVA pacing for 3 months was sufficient to induce a cellular phenotype similar to that seen in heart failure. Less dramatic changes were seen with RVOT pacing. This provides evidence for the development of PiCM at an early stage, prior to the development of echocardiographic remodelling.

Table.

LV Free Wall Calcium Handling

Disease model (cells/subjects) Diastolic [Ca] (n.u.) Systolic [Ca] (n.u.) [Ca] Transient (Ratio) [Ca] Decay (/s)
Control (55/26) 0.56 (0.02) 1.09 (0.06) 1.93 (0.06) 4.16 (0.27)
RVA Paced (19/10) 0.52 (0.03) 0.77 (0.05)* 1.48 (0.05)* 3.27 (0.35)*
RVOT Paced (10/5) 0.65 (0.05)* 1.10 (0.10) 1.68 (0.08) 2.72 (0.22)*
Heart Failure (10/9) 0.39 (0.05)* 0.51 (0.08)** 1.32 (0.07)** 2.32 (0.32)*
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Mean (SEM) *p < 0.05 **p < 0.005 (ANOVA vs control)

Europace. 2016 Feb 22;17(Suppl 5):v3–v5.

16: A steep apd-restitution slope does not cause apd-alternans in the intact human heart

M Orini 1, P Taggart 1, B Hanson 2, M Hayward 3, PD Lambiase 1

Abstract

Introduction: A periodical change in the duration of the action potential, so called action potential duration alternans (APDA), is a precursor of ventricular fibrillation and it is associated with an increased risk of sudden cardiac death. The underlying mechanisms of APDA are still undetermined. The APD-restitution slope (APDRS) measures the interaction between the electrical diastole (DI) and systole (APD). Based on a simple mathematical model, a steep restitution curve has been proposed as an underlying mechanism of APDA. The aim of this study was to describe the spatial distribution of APDA and APDRS as well as their interaction in the intact human heart.

Method: We used a multielectrode sock (240 channels) to perform whole heart epicardial mapping in 31 patients undergoing cardiac surgery. APDA was induced by rapid ventricular pacing at cycle lengths (CLs) of 600, 550, 500, 450, 400 and 350 ms. Each train of stimuli was 30-45 ms long. APD was measured as activation recovery interval in the unipolar electrogrms, and APDA susceptible and resistant sites were localized during online analysis. S1-S2 restitution protocols were performed in 7 patients by pacing immediately adjacent to the APDA susceptible and resistant sites.

Results: APDA was spatially heterogeneous in all patients (Fig. A1). The number of sites exhibiting APDA and the relative magnitude of APDA increased for shorter CLs (Fig. A2-3).

The number of sites exhibiting APDA (at least at one CL) in the left and right ventricles was equivalent, as it was between apex and base (Fig. A4). APDA was observed over a range of CLs corresponding to the APD restitution curve plateau.

The APDRS was also spatially heterogeneous (Fig. B1). More than 50% of cardiac sites were characterized by an APDRS > 1. There was no difference in either APDRS or the number of curves with APDRS >1 between alternans susceptible and resistant sites (Fig. B2-3).

Conclusion: This study demonstrates: (1) Regionality of APDA in human epicardium for the first time. (2) Heart rate dependency of APDA. (3) Similar prevalence of APDA in the apex and base and in the left and right ventricles. (4) APDA is unrelated to the steepness of the APD restitution slope. This indicates that alternative mechanisms are operative and accessible by this experimental approach.

graphic file with name euv32503.jpg

Figure (A1) Hetherogeneous spatial distribution of APDA. (A2-3) Heart rate dependency of APDA. (A4) No apico-basal or RV-LV differences in APDA. (B1) Restitution curves (examples). (B2-3) Comparison of APDRS

Europace. 2016 Feb 22;17(Suppl 5):v3–v5.

17: Cardiac sites of the in-vivo human heart exhibiting apd-alternans show changes in calcium-handling proteins and repolarizing currents

PD Lambiase 1, J Yanni 2, M Orini 1, B Hanson 3, M Hayward 4, A Smith 4, H Zhang 2, H Dobrzynski 2, M Boyett 2, P Taggart 1

Abstract

Introduction: Action potential duration alternans (APDA) is a precursor of ventricular fibrillation and is associated with sudden cardiac death. The underlying mechanisms of APDA are still undetermined. The aim of this study was to identify the molecular basis of APDA in the in-vivo human heart, using a novel experimental approach that combines whole heart electrophysiological mapping during cardiac surgery with rapid on-site data analysis to guide myocardial biopsies.

Methods: We used a multielectrode sock (240 channels) to perform whole heart epicardial mapping in 17 patients undergoing cardiac surgery (mean age 62.5 ± 15, 28M:3F, 22 ischemic heart disease, 5 aortic valve disease & 4 with both). APDA was induced by rapid ventricular pacing at cycle lengths (CLs) of 600, 550, 500, 450, 400 and 350 ms. Each train of stimuli was 30-45 ms long. APD was measured as activation recovery interval in the unipolar electrogrms, and APDA susceptible and resistant sites were localized during rapid online analysis. Targeted biopsies were taken to examine mRNA expression of ion channels and related molecules in the alternans susceptible and resistant sites identified during online analysis (fig A). The ten Tusscher biophysical model utilising the mRNA data was employed to elucidate the mechanisms that link cellular properties and APDA.

Results: mRNA expression studies (n = 13) demonstrated relatively uniform increases in the ion channels underlying INa, ICa,L, INaCa, Ito, IK,s and IK,1 and five Ca2+-handling molecules (RYR2, calsequestrin2, SERCA2, phospholamban and NCX1) at alternans-susceptible sites, with supportive protein expression data (western blot). Biophysical model utilising the mRNA expression data predicted alternans in the same range of cycle lengths observed in vivo, principally determined by the local increase in Cav1.2 (underlying ICa,L) and RYR2 (Fig. B).

Conclusion: We introduce a novel approach that combines whole heart and cellular electrophysiology in humans and demonstrate that APD alternans is associated with the greater expression of several Ca2+ handling and repolarizing currents in the in vivo heart. A biophysical model indicates that APD alternans was principally determined by the local increase in Cav1.2 (underlying ICa,L) and RYR2.

A: Mapping of APD alternans, red regions correspond to APDA. (B) Expression of mRNAs for RyR2 and CaV1.2 at the alternans-susceptible (red bar) and alternans-resistant (blue bar) sites. Means (+SEM) shown (n = 13 patients). **P < 0.005; *0.005 < P < 0.05. In total, 18 components show significant differences. The computer simulations suggest that the most important changes in the alternans-susceptible tissue are a greater expression of Cav1.2 and RYR2. (C) Action potentials computed from the ventricular myocyte model at a cycle length of 600 ms. There was no alternans in the control condition, but clear alternans in the alternans-susceptible condition, which was associated with EADs.

graphic file with name euv32504.jpg

Europace. 2016 Feb 22;17(Suppl 5):v3–v5.

18: Dynamic transmural activation recovery interval gradients exceed apico-basal gradients in the intact human heart

NT Srinivasan 1, M Orini 1, RB Simon 1, R Providencia 1, G Babu 1, S Vyas 1, F Khan 1, T Chow 1, OR Segal 1, MD Lowe 1, PD Lambiase 1

Abstract

Introduction: The action potential restitution properties of the heart govern the potential risk of arrhythmia. Although restitution in known to vary with different protocols, little known about how this behaviour varies in different regions of the the intact human heart.

Methods: Restitution was studied in 10 patients (60% female) with structurally normal hearts. Decapolar diagnostic EP catheters were placed in the anterior Right Ventricle (RV), lateral the left ventricle (LV) in an apico-basal orientation and epicardially via the LV branch of the coronary sinus (CS) for transmural measurement. Pacing was commensed at the Apex of the RV, the base of the LV endocardium and the base of the LV epicardium at basic cycle length (BCL) of 600ms, followed by S1-S2 restitution protocol. Activation recovery intervals (ARIs) were recorded as a surrogate of action potential duration, starting with S2 stimulus at 1000ms and decrementing to refractory period of the tissue.

Results: Mean age was 45 +/−15yrs. Loess regression, with 95% confidence intervals of restitution, showed shorter Epicardial ARI's throughout restitution when compared to the LV endocardium. Quantile Regression of Transmural ARI gradient's are shown in Fig. 1 (g-i) where a significantly shorter ARI's across the whole of the restitution curve are seen regardless of pacing site (p-values seen within graph, arrows depict ARI difference at 50th quantile). Apico-basal ARI's in the RV and LV endocardium showed no significant gradient (Fig. 1a-d &e.) except when pacing was conducted in the basal LV (Fig. 1e. p = 0.02, 20ms gradient at the 50th quantile). 725 restitution slopes were analysed. Slope gradients were >1 in 74% of tracings (median 1.54 +/−0.14). Negative global AT/ARI coupling was present during sinus rhythm (p = <0.05) and RV apical pacing (p = <0.05), but not when pacing the LV at the basal endocardium or epicardium.

Conclusion: Transmural ARI gradients within the ventricle LV are present in normal patients, without significant apico-basal ARI gradients. Restitution slopes appear to be consistently steeper than > 1 in normal healthy ventricles. Negative AT/ARI coupling was not present during pacing of the LV base endocardially and epicardially. This data has important implications in modelling conduction-repolarsation kinetics in the intact human heart.

Figure 1 Lowes regrssion of Apicobasal (a-f) vs Transmural Gradients (g-i) of ARI during restitution pacing from the RV apex (a,d&g), LV endocardium at the base (b,e&h) and the LV epicardium at the base (c,f&i). P-values based on quantile regression, with significance only stated of p < 0.05 for the entire restitution curve. Arrows represent the gradient at the 50th quartile.

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