Optimizing safety and efficacy of catheter ablation procedures

Abstract In this thesis new developments in the field of invasive electrophysiology are studied and discussed. The aim of this work is to find strategies to optimize safety and efficacy of catheter ablation procedures. The most important developments that are studied in this thesis are the magnetic navigation system, the use of contact force sensing catheters and the introduction of new gold-tip ablation catheters. ROBOTICS: In Part I of this thesis we discussed the use of the first available magnetic navigation system. CONTACT FORCE SENSING: In Part II of this thesis the use of contact force sensing catheters is studied. The success of catheter ablation procedures depends on accurate substrate localization, followed by optimal delivery of energy provided by good tissue contact. LESION FORMATION: The introduction of the irrigated-tip RF catheter was a great improvement for invasive electrophysiology and increased success rates for many arrhythmias compared to nonirrigated-tip catheters. FUTURE PERSPECTIVES: In this thesis new developments in the field of invasive electrophysiology are discussed to optimize safety and efficacy of catheter ablation procedures

Arrayed-waveguide-grating light collector for on-chip spectroscopy

We present a novel arrayed-waveguide-grating (AWG) device with improved external (biomedical) signal collection for use in on-chip spectroscopy. The collection efficiency of the device is compared to that of a standard AWG. We also present experimental results on the collection efficiency and size of the collection volume

Integrated AWG spectrometer for on-chip optical coherence tomography and Raman spectroscopy

Silicon oxynitride-based arrayed waveguide grating (AWG) spectrometers were designed for on-chip spectral-domain optical coherence tomography (OCT) systems and Raman spectroscopy of the skin. A novel geometrical layout for Raman spectroscopy was introduced to reduce loss. Measurements show that integrated optics has a good potential for miniaturizing current OCT systems

The first human experience of a contact force sensing catheter for epicardial ablation of ventricular tachycardia

Contact force (CF) is one of the major determinants for sufficient lesion formation. CF-guided procedures are associated with enhanced lesion formation and procedural success.We report our initial experience in epicardial ventricular tachycardia (VT) ablation with a force-sensing catheter using a new approach with an angioplasty balloon. Two patients with arrhythmogenic right ventricular cardiomyopathy who underwent prior unsuccessful endocardial ablation were treated with epicardial VTablation. CF data were used to titrate force, power and ablation time

Extreme interatrial conduction delay and regularization of atrial arrhythmias in a subgroup of patients with hypertrophic cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) patients may develop interatrial activation delay, indicated by a complete separation of the right and left atrial activation on the ECG. This study aimed to determine the prevalence of interatrial activation delay and the relation to atrial tachycardia (AT) cycle length (CL) in HCM patients. Methods: 159 HCM patients were included (mean age 52±14y). In group I (n=15, 9%) patients had atrial arrhythmias and progressive ATCL. In group II (n=22, 14%) patients had a stable ATCL. In group III (n=122, 77%) HCM patients without AT were included. P wave morphology and change in P wave duration (δP and Pmax) and changes in ATCL (δATCL) were analyzed. Mean follow-up was 8.7±4.7years. Results: In group I 33% (n=5) had separated P waves. In group II no P wave separation was identified (OR 1.50 [1.05-2.15], p=0.007). In group I patients were older compared to group III (62.6±15.1 vs. 50.2±14.0y, p=0.002) and had longer follow-up (13.4±2.2 vs. 7.8±4.6y, p<0.001). In group III Pmax and δP were significantly lower (105.1±22.0ms and 8.9±13.2ms, both p<0.0001). Group I patients had an increased LA size compared to group II (61.1±11.6 vs. 53.7±7.5mm, p=0.028) and higher E/A and E/E prime ratios (p=0.007; p=0.037, respectively). In group I 93.3% of the identified mutations were typical Dutch founder mutations of the MYBPC3 gene. Conclusion: In HCM patients a unique combination of separated P waves and regularization of ATs is associated with larger atria, higher LA pressures and myosin binding protein mutations

Haemolysis as a first sign of thromboembolic event and acute pump thrombosis in patients with the continuous-flow

Background Despite advances in pump technology, thromboembolic events/acute pump thrombosis remain potentially life-threatening complications in patients with continuous-flow left ventricular assist devices (CF-LVAD). We sought to determine early signs of thromboembolic event/ pump thrombosis in patients with CF-LVAD, which could lead to earlier intervention. Methods We analysed all HeartMate II recipients (n = 40) in our centre between December 2006 and July 2013. Thromboembolic event/pump thrombosis was defined as a transient ischaemic attack (TIA), ischaemic cerebrovascular accident (CVA), or pump thrombosis. Results During median LVAD support of 336 days [IQR: 182–808], 8 (20%) patients developed a thromboembolic event/pump thrombosis (six TIA/CVA, two pump thromboses). At the time of the thromboembolic event/pump thrombosis, significantly higher pump power was seen compared with the no-thrombosis group (8.2 ± 3.0 vs. 6.4 ± 1.4 W, p = 0.02), as well as a trend towards a lower pulse index (4.1 ± 1.5 vs. 5.0 ± 1.0, p = 0.05) and a trend towards higher pump flow (5.7 ± 1.0 vs. 4.9 ± 1.9 L m, p = 0.06). The thrombosis group had a more than fourfold higher lactate dehydrogenase (LDH) median 1548 [IQR: 754– 2379] vs. 363 [IQR: 325–443] U/L, p = 0.0001). Bacterial (n = 4) or viral (n = 1) infection was present in 5 out of 8 patients. LDH > 735 U/L predicted thromboembolic events/ pump thrombosis with a positive predictive value of 88%. Conclusions In patients with a CF-LVAD (HeartMate II), thromboembolic events and/or pump thrombosis are associated with symptoms and signs of acute haemolysis as manifested by a high LDH, elevated pump power and decreased pulse index, especially in the context of an infection

Clinical outcome of ablation for long-standing persistent atrial fibrillation with or without defragmentation

Objective To assess the outcome and associated risks of atrial defragmentation for the treatment of long-standing persistent atrial fibrillation (LSP-AF). Methods Thirty-seven consecutive patients (60.4±7.3 years; 28 male) suffering from LSP-AF who underwent pulmonary vein isolation (PVI) and linear ablation were compared. All patients were treated with the Stereotaxis magnetic navigation system (MNS). Two groups were distinguished: patients with (n =20) and without (n =17) defragmentation. The primary endpoint of the study was freedom of AF after 12 months. Secondary endpoints were AF termination, procedure time, fluoroscopy time and procedural complications. Complications were divided into two groups: Major (infarction, stroke, major bleeding and tamponade) and minor (fever, pericarditis and inguinal haematoma). Results No difference was seen in freedom of AF between the defragmentation and the non-defragmentation group (56.2 % vs. 40.0%, P=0.344). Procedure times in the defragmentation group were longer; no differences in fluoroscopy times were observed. No major complications occurred. A higher number of minor complications occurred in the defragmentation group (45.0 % vs. 5.9 %, P=0.009). Mean hospital stay was comparable (4.7±2.2 vs. 3.4±0.8 days, P=0.06). Conclusion Our study suggests that complete defragmentation using MNS is associated with a higher number of minor complications and longer procedure times and thus compromises efficiency without improving efficacy

Cardiac allograft vasculopathy and donor age affecting permanent pacemaker implantation after heart transplantation

AIMS: The need for permanent pacemakers (PMs) after heart transplantation (HT) is increasing. The aim was to determine the influence of cardiac allograft vasculopathy (CAV), donor age, and other risk factors on PM implantations early and late after HT and its effect on survival. METHODS AND RESULTS: A retrospective, single‐centre study was performed including HTs from 1984 to July 2018. Early PM was defined as PM implantation ≤90 days and late PM as PM > 90 days. Risk factors for PM and survival after PM were determined with (time‐dependent) multivariable Cox regression. Out of 720 HTs performed, 62 were excluded (55 mortalities ≤30 days and 7 retransplantations). Of the remaining 658 patients, 95 (14%) needed a PM: 38 (6%) early and 57 (9%) late during follow‐up (median 9.3 years). Early PM risk factors were donor age [hazard ratio (HR) 1.06, P < 0.001], ischaemic time (HR 1.01, P < 0.001), and in adults amiodarone use before HT (HR 2.02, P = 0.045). Late PM risk factors were donor age (HR 1.03, P = 0.024) and CAV (HR 3.59, P < 0.001). Late PM compromised survival (HR 2.05, P < 0.001), while early PM did not (HR 0.77, P = 0.41). CONCLUSIONS: Risk factors for early PM implantation were donor age, ischaemic time, and in adults amiodarone use before HT. Late PM implantation risk factors were donor age and CAV. Late PM diminished survival, which is probably a surrogate marker for underlying progressive cardiac disease

Benefits and harms of perioperative high fraction inspired oxygen for surgical site infection prevention: a protocol for a systematic review and meta-analysis of individual patient data of randomised controlled trials.

INTRODUCTION The use of high fraction of inspired oxygen (FiO2) intraoperatively for the prevention of surgical site infection (SSI) remains controversial. Promising results of early randomised controlled trials (RCT) have been replicated with varying success and subsequent meta-analysis are equivocal. Recent advancements in perioperative care, including the increased use of laparoscopic surgery and pneumoperitoneum and shifts in fluid and temperature management, can affect peripheral oxygen delivery and may explain the inconsistency in reproducibility. However, the published data provides insufficient detail on the participant level to test these hypotheses. The purpose of this individual participant data meta-analysis is to assess the described benefits and harms of intraoperative high FiO2compared with regular (0.21-0.40) FiO2 and its potential effect modifiers. METHODS AND ANALYSIS Two reviewers will search medical databases and online trial registries, including MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov and WHO regional databases, for randomised and quasi-RCT comparing the effect of intraoperative high FiO2 (0.60-1.00) to regular FiO2 (0.21-0.40) on SSI within 90 days after surgery in adult patients. Secondary outcome will be all-cause mortality within the longest available follow-up. Investigators of the identified trials will be invited to collaborate. Data will be analysed with the one-step approach using the generalised linear mixed model framework and the statistical model appropriate for the type of outcome being analysed (logistic and cox regression, respectively), with a random treatment effect term to account for the clustering of patients within studies. The bias will be assessed using the Cochrane risk-of-bias tool for randomised trials V.2 and the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. Prespecified subgroup analyses include use of mechanical ventilation, nitrous oxide, preoperative antibiotic prophylaxis, temperature (2.5 hour). ETHICS AND DISSEMINATION Ethics approval is not required. Investigators will deidentify individual participant data before it is shared. The results will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER CRD42018090261