Prevention and Management of Cardiac Implantable Electronic Device Infections: State-of-the-Art and Future Directions.

Cardiac implantable electronic device (CIED) infection is an increasingly common complication of device therapy. CIED infection confers significant patient morbidity and health care expenditure, hence it is essential that clinicians recognise the contemporary strategies for predicting, reducing and treating these events. Recent technological advances-in particular, the development of antimicrobial envelopes, leadless devices and validated risk scores-present decision-makers with novel strategies for managing this expanding patient population. This review summarises the key issues facing CIED patients and their physicians, and explores the supporting evidence for the latest therapeutic developments in this field.

Long-term outcomes of index cryoballoon ablation or point-by-point radiofrequency ablation in patients with atrial fibrillation and systolic heart failure.

Catheter ablation is an established effective approach for the treatment of atrial fibrillation (AF) in patients with heart failure, however, the role of cryoablation in this setting is unclear. Procedural success and left ventricular systolic dysfunction (LVEF) improvement in patients with LVEF ≤ 45% undergoing index catheter ablation with cryoablation were evaluated. Freedom from AF recurrence was seen in 43% rising to 59% following repeat procedure. There were significant improvements in LVEF and functional status at long-term follow-up. Results were comparable to a contemporaneous cohort of heart failure patients undergoing index ablation with radiofrequency ablation. Cryoablation is an effective first-line AF ablation approach in the setting of heart failure.

Validation of a novel mapping system and utility for mapping complex atrial tachycardias.

INTRODUCTION: This study sought to validate a novel wavefront mapping system utilizing whole-chamber basket catheters (CARTOFINDER, Biosense Webster). The system was validated in terms of (1) mapping atrial-paced beats and (2) mapping complex wavefront patterns in atrial tachycardia (AT). METHODS AND RESULTS: Patients undergoing catheter ablation for AT and persistent AF were included. A 64-pole-basket catheter was used to acquire unipolar signals that were processed by CARTOFINDER mapping system to generate dynamic wavefront propagation maps. The left atrium was paced from four sites to demonstrate focal activation. ATs were mapped with the mechanism confirmed by conventional mapping, entrainment, and response to ablation. Twenty-two patients were included in the study (16 with AT and 6 with AF initially who terminated to AT during ablation). In total, 172 maps were created with the mapping system. It correctly identified atrial-pacing sites in all paced maps. It accurately mapped 9 focal/microreentrant and 18 macroreentrant ATs both in the left and right atrium. A third and fourth observer independently identified the sites of atrial pacing and the AT mechanism from the CARTOFINDER maps, while being blinded to the conventional activation maps. CONCLUSIONS: This novel mapping system was effectively validated by mapping focal activation patterns from atrial-paced beats. The system was also effective in mapping complex wavefront patterns in a range of ATs in patients with scarred atria. The system may therefore be of practical use in the mapping and ablation of AT and could have potential for mapping wavefront activations in AF.

Left atrial scarring and conduction velocity dynamics: Rate dependent conduction slowing predicts sites of localized reentrant atrial tachycardias.

BACKGROUND: Low voltage zones (LVZs) are associated with conduction velocity (CV) slowing. Rate-dependent CV slowing may play a role in reentry mechanisms. METHODS: Patients undergoing catheter ablation for AT were enrolled. Aim was to assess the relationship between rate-dependent CV slowing and sites of localized reentrant atrial tachycardias (AT). On a bipolar voltage map regions were defined as non-LVZs [≥0.5 mV], LVZs [0.2-0.5 mV] and very-LVZs [<0.2 mV]. Unipolar electrograms were recorded with a 64-pole basket catheter during uninterrupted atrial pacing at four pacing intervals (PIs) during sinus rhythm. CVs were measured between pole pairs along the wavefront path. Sites of rate-dependent CV slowing were defined as exhibiting a reduction in CV between PI = 600 ms and 250 ms of ≥20% more than the mean CV reduction seen between these PIs for that voltage zone. Rate-dependent CV slowing sites were correlated to sites of localized reentrant ATs as confirmed with conventional mapping, entrainment and response to ablation. RESULTS: Eighteen patients were included (63 ±â€¯10 years). Mean CV at 600 ms was 1.53 ±â€¯0.19 m/s in non-LVZs, 1.14 ±â€¯0.15 m/s in LVZs, and 0.73 ±â€¯0.13 m/s in very-LVZs respectively (p < 0.001). Rate-dependent CV slowing sites were predominantly in LVZs [0.2-0.5 mV] (74.4 ±â€¯10.3%; p < 0.001). Localized reentrant ATs were mapped to these sites in 81.8% of cases (sensitivity 81.8%, 95% CI 48.2-97.9% and specificity 83.9%, 95% CI 81.8-86.0%). Macro-reentrant or focal ATs were not mapped to sites of rate-dependent CV slowing. CONCLUSIONS: Rate-dependent CV slowing sites are predominantly confined to LVZs [0.2-0.5 mV] and the resultant CV heterogeneity may promote reentry mechanisms. These may represent a novel adjunctive target for AT ablation.

Impact of attributed audit on procedural performance in cardiac electrophysiology catheter laboratory.

PURPOSE: Audit has played a key role in monitoring and improving clinical practice. However, audit often fails to drive change as summative institutional data alone may be insufficient to do so. We hypothesised that the practice of attributed audit, wherein each individual's procedural performance is presented will have a greater impact on clinical practice. This hypothesis was tested in an observational study evaluating improvement in fluoroscopy times for AF ablation. METHODS: Retrospective analyses of fluoroscopy times in AF ablations at the Barts Heart Centre (BHC) from 2012-2017. Fluoroscopy times were compared pre- and post- the introduction of attributed audit in 2012 at St Bartholomew's Hospital (SBH). In order to test the hypothesis, this concept was introduced to a second group of experienced operators from the Heart Hospital (HH) as part of a merger of the two institutions in 2015 and change in fluoroscopy times recorded. RESULTS: A significant drop in fluoroscopy times (33.3 ± 9.14 to 8.95 ± 2.50, p < 0.0001) from 2012-2014 was noted after the introduction of attributed audit. At the time of merger, a significant difference in fluoroscopy times between operators from the two centres was seen in 2015. Each operator's procedural performance was shared openly at the audit meeting. Subsequent audits showed a steady decrease in fluoroscopy times for each operator with the fluoroscopy time (min, mean±SD) decreasing from 13.29 ± 7.3 in 2015 to 8.84 ± 4.8 (p < 0.0001) in 2017 across the entire group. CONCLUSIONS: Systematic improvement in fluoroscopy times for AF ablation procedures was noted byevaluating individual operators' performance. Attributing data to physicians in attributed audit can promptsignificant improvement and hence should be adopted in clinical practice.

Moderate sedation in cardiac electrophysiology laboratory: a retrospective safety analysis.

OBJECTIVE: Cardiac electrophysiology (EP) procedures can be performed under moderate sedation without the direct involvement of an anaesthetist. However, concerns have been raised over the safety of this approach. This study examines the use of a standardised nurse-led physician-directed sedation protocol for EP procedures to determine the safety of moderate sedation administered by non-anaesthesia personnel who have been trained in sedation techniques. METHODS AND RESULTS: Consecutive EP procedures done under moderate sedation over 12 years at our institution were evaluated. Serious adverse events were defined as (i) procedural death related to sedation; (ii) intubation and ventilation; and (iii) hypotension requiring inotropic support. Reversal of sedation constituted a minor adverse event. Up to 7117 procedures were included. These comprised ablations (55%), devices (43%) and other procedures (2%). A majority of patients were men with a mean age of 61±10 years. 99.98% of procedures were completed successfully without sedation-related serious adverse events. Two patients (0.02%) required anaesthetic support for intubation. Sedation was reversed in 1.2% of procedures with less than 1% requiring reversal because of persistent drop in oxygen saturation, hypoventilation or markedly reduced level of consciousness. There was no significant difference in the patient characteristics, mean doses of sedative agents and procedure types in the group requiring reversal of sedation when compared with the whole cohort. CONCLUSIONS: Our study demonstrates that nurse-led, physician-directed moderate sedation is safe. Anaesthesia services are not required routinely for invasive cardiac EP procedures and should be available on a need basis.

Safety and efficacy of paramedic treatment of regular supraventricular tachycardia: a randomised controlled trial.

INTRODUCTION: Supraventricular tachycardias (SVTs) are a common cause of acute hospital presentations. Adenosine is an effective treatment. To date, no studies have directly compared paramedic-with hospital-delivered treatment of acute SVT with adenosine. METHOD: Randomised controlled trial comparing the treatment of SVT and discharge by paramedics with conventional emergency department (ED)-based care. Patients were excluded if they had structural heart disease or contraindication to adenosine. Discharge time, follow-up management, costs and patient satisfaction were compared. RESULTS: Eighty-six patients were enrolled: 44 were randomised to paramedic-delivered adenosine (PARA) and 42 to conventional care (ED). Of the 37 patients in the PARA group given adenosine, the tachycardia was successfully terminated in 81%. There was a 98% correlation between the paramedics' ECG diagnosis and that of two electrophysiologists. No patients had any documented adverse events in either group. The discharge time was lower in the PARA group than in the ED group (125 min (range 55-9513) vs 222 min (range 72-26 153); p=0.01), and this treatment strategy was more cost-effective (£282 vs £423; p=0.01). The majority of patients preferred this management approach. Being treated and discharged by paramedics did not result in the patients being less likely to receive ongoing management of their arrhythmia and cardiology follow-up. CONCLUSIONS: Patients with SVT can effectively and safely be treated with adenosine delivered by trained paramedics. Implementation of paramedic-delivered acute SVT care has the potential to reduce healthcare costs without compromising patient care. TRIAL REGISTRATION NUMBER: NCT02216240.

A propensity matched case-control study comparing efficacy, safety and costs of the subcutaneous vs. transvenous implantable cardioverter defibrillator.

BACKGROUND: Subcutaneous implantable cardioverter defibrillators (S-ICD) have become more widely available. However, comparisons with conventional transvenous ICDs (TV-ICD) are scarce. METHODS: We conducted a propensity matched case-control study including all patients that underwent S-ICD implantation over a five-year period in a single tertiary centre. Controls consisted of all TV-ICD implant patients over a contemporary time period excluding those with pacing indication, biventricular pacemakers and those with sustained monomorphic ventricular tachycardia requiring anti-tachycardia pacing. Data was collected on device-related complications and mortality rates. A cost efficacy analysis was performed. RESULTS: Sixty-nine S-ICD cases were propensity matched to 69 TV-ICD controls. During a mean follow-up of 31±19 (S-ICD) and 32±21months (TV-ICD; p=0.88) there was a higher rate of device-related complications in the TV-ICD group predominantly accounted for by lead failures (n=20, 29% vs. n=6, 9%; p=0.004). The total mean cost for each group, including the complication-related costs was £9967±4511 ($13,639±6173) and £12,601±1786 ($17,243±2444) in the TV-ICD and S-ICD groups respectively (p=0.0001). Even though more expensive S-ICD was associated with a relative risk reduction of device-related complication of 70% with a HR of 0.30 (95%CI 0.12-0.76; p=0.01) compared to TV-ICDs. CONCLUSIONS: TV-ICDs are associated with increased device-related complication rates compared to a propensity matched S-ICD group during a similar follow-up period. Despite the existing significant difference in unit cost of the S-ICD, overall S-ICD costs may be mitigated versus TV-ICDs over a longer follow-up period.

Contact Force and Atrial Fibrillation Ablation.

Catheters able to measure the force and vector of contact between the catheter tip and myocardium are now available. Pre-clinical work has established that the degree of contact between the radiofrequency ablation catheter and myocardium correlates with the size of the delivered lesion. Excess contact is associated with steam pops and perforation. Catheter contact varies within the left atrium secondary to factors including respiration, location, atrial rhythm and the trans-septal catheter delivery technology used. Compared with procedures performed without contact force (CF)-sensing, the use of this technology has, in some studies, been found to improve complication rates, procedure and fluoroscopy times, and success rates. However, for each of these parameters there are also studies suggesting a lack of difference from the availability of CF data. Nevertheless, CF-sensing technology has been adopted as a standard of care in many institutions. It is likely that use of CF-sensing technology will allow for the optimization of each individual radiofrequency application to maximize efficacy and procedural safety. Recent work has attempted to define what these optimal targets should be, and approaches to do this include assessing for sites of pulmonary vein reconnection after ablation, or comparing the impedance response to ablation. Based on such work, it is apparent that factors including mean CF, force time integral (the area under the force-time curve) and contact stability are important determinants of ablation efficacy. Multicenter prospective randomized data are lacking in this field and required to define the CF parameters required to produce optimal ablation.

Management of atrial fibrillation: when are invasive approaches useful?

The management of atrial fibrillation extends from stroke prevention to rate or rhythm control strategies. The role of an invasive strategy is expanding and it remains important to identify suitable candidates early in the disease process.

Epicardial catheter ablation for ventricular tachycardia on uninterrupted warfarin: A safe approach for those with a strong indication for peri-procedural anticoagulation?

BACKGROUND: Current guidelines for epicardial catheter ablation for ventricular tachycardia (VT) advocate that epicardial access is avoided in anticoagulated patients and should be performed prior to heparinisation. Recent studies have shown that epicardial access may be safe in heparinised patients. However, no data exist for patients on oral anticoagulants. We investigated the safety of obtaining epicardial access on uninterrupted warfarin. METHODS: A prospective registry of patients undergoing epicardial VT ablation over two years was analysed. Consecutive patients in whom epicardial access was attempted were included. All patients were heparinised prior to epicardial access with a target activated clotting time (ACT) of 300-350s. Patients who had procedures performed on uninterrupted warfarin (in addition to heparin) were compared to those not taking an oral anticoagulant. RESULTS: 46 patients were included of which 13 were taking warfarin. There was no significant difference in clinical and procedural characteristics (except INR and AF) between the two groups. Epicardial access was achieved in all patients. There were no deaths and no patients required surgery. A higher proportion of patients in the warfarin group had a drop in haemoglobin of >2g/dL compared to the no-warfarin group (38.5% versus 27.3%, p=0.74) and delayed pericardial drain removal (7.8% versus 3.03%, p=0.47). There was no difference in overall procedural complication rate. No patients required warfarin reversal or blood transfusion. CONCLUSION: Epicardial access can be achieved safely and effectively in patients' anticoagulated with warfarin and heparinised with therapeutic ACT. This may be an attractive option for patients with a high stroke risk.

Telomere shortening and telomerase activity in ischaemic cardiomyopathy patients - Potential markers of ventricular arrhythmia.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) reduce mortality in patients with ischaemic cardiomyopathy at high risk of ventricular arrhythmias (VA). However, the current indication for ICD prescription needs improvement. Telomere and telomerase in leucocytes have been shown to associate with biological ageing and pathogenesis of cardiovascular diseases. We hypothesised that leucocyte telomere length, load-of-short telomeres and/or telomerase activity are associated with VA occurrence in ischaemic cardiomyopathy patients. METHODS AND RESULTS: 90 ischaemic cardiomyopathy patients with primary prevention ICDs were recruited. 35 had received appropriate therapy from the ICD for potentially-fatal VA while the remaining 55 patients had not. No significant differences in baseline demographic data relevant to telomere biology were seen between the two groups. There was no significant difference in the age and sex adjusted mean telomere length analysed by qPCR between the groups (p=0.88). In contrast, the load-of-short telomeres assessed by Universal-STELA method and telomerase activity by TRAP assay were both higher in patients who had appropriate ICD therapy and were significantly associated with incidence of ICD therapy (p=0.02, p=0.02). ROC analyses demonstrated that the sensitivity and specificity of these telomere dynamics in predicting potentially-fatal VA was higher than the current gold-standard - left ventricular ejection fraction (AUC 0.82 versus 0.47). CONCLUSION: The load-of-short telomeres and telomerase activity had a significant association with ICD therapy (for VA) in ischaemic cardiomyopathy patients. These biomarkers should be tested in prospective studies to assess their clinical utility in predicting VA after myocardial infarction and guiding primary prevention ICD prescription.

A mechanism for ethanol-induced damage to liver mitochondrial structure and function.

Mitochondria isolated from rats chronically fed ethanol demonstrated a marked inability to produce energy. The respiratory control ratio, the ADP/O ratio and state 3 respiration rates were all decreased. Coupled with other data, a progression of ethanol-induced changes is proposed with site I being altered prior to site II. Quantitation of mitochondrial cytochromes revealed decreases in cytochromes b and aa3 and an increase in c1. Evaluation of respiration activity in relation to temperature showed ethanol-induced changes in the transition temperature (Tf) which may have been related to changes in the lipid composition of the inner membrane. Mitochondrial membranes were separated, and analysis of fatty acids and phospholipids was performed. Various fatty acids were altered in both membranes; however, the outer membrane was altered more severely. A decrease in the arachidonate : linoleate ratio was observed only in the outer membrane; however, there was no ethanol-induced change in degree of unsaturation in either membrane. Phospholipid quantitation showed a reduction of total lipid phosphorous/mg protein in both membrane fractions; however, the inner membrane was most affected. Cardiolipin was the only phospholipid in this membrane which remained unaltered. The evidence indicates that the mechanism for ethanol-induced damage to the liver mitochondrion involves lipid compositional changes as well as changes in cytochromes and possibly other proteins.

2',3'-cyclic nucleotide 3'-phosphohydrolase in rat liver mitochondrial membranes.

2',3'-Cyclic nucleotide 3'-phosphohydrolase (nucleoside-2':3'-cyclic-phosphate 2'-nucleotidohydrolase, EC 3.1.4.37) activity has been demonstrated in rat liver mitochondria. The enzyme was localized in both the outer and inner mitochondrial membranes but was absent from the intermembrane space and matrix. The mitochondrial (cyclic nucleotide) phosphohydrolase was activated by freezing and thawing and by treatment with digitonin or detergents. It is suggested that (cyclic nucleotide) phosphohydrolase is an integral membrane protein which is buried to a significant degree within the membrane. Atractyloside was found to be a noncompetitive inhibitor of the enzyme both in intact mitochondria and in preparations of the mitochondrial membranes. The enzyme substrate, 2',3'-cyclic adenosine monophosphate, had no effect on the oxidation of exogenous beta-hydroxybutyrate or succinate by intact mitochondria. These findings suggest that 2',3'-cyclic nucleotide 3'phosphohydrolase is more widely distributed than was previously thought and that the enzyme may play a fundamental role in membranes, independent of their specialized structure or functions.

Effects of chronic ethanol ingestion on the activity of rat liver mitochondrial 2',3'-cyclic nucleotide 3'-phosphohydrolase.

Chronic ethanol ingestion induced a 47% increase in the specific activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase (nucleoside-2':3'-cyclic-phosphate 2'-nucleotidohydrolase, EC 3.1.4.37) in whole mitochondria. Both inner and outer mitochondrial membranes showed increased (cyclic nucleotide)phosphohydrolase activity, but the inner was increased 94% compared to 67% for the outer. Techniques which disrupt membrane structure increased (cyclic nucleotide)phosphohydrolase activity. After these treatments, whole mitochondria from ethanol-treated animals still showed a 50% increase in activity. This increase may be related either to an inherent increase in the resistance of (cyclic nucleotide)phosphohydrolase to protein degradation or turnover, or to ethanol-induced membrane changes. An increase in (cyclic nucleotide)phosphohydrolase reaction medium pH was observed when freshly isolated, highly-coupled mitochondria were used. The total increase in pH was about 2-fold greater in the controls compared to the ethanol-treated mitochondria. It is suggested that the smaller initial increase in pH and the greater activity of (cyclic nucleotide)phosphohydrolase in the mitochondria from the ethanol-treated animals relate to previously observed changes in the lipid and protein composition of the mitochondrial membranes. In addition, (cyclic nucleotide)phosphohydrolase may represent an excellent marker for membrane integrity.