The role of cardiac MRI in the management of ventricular arrhythmias in ischaemic and non-ischaemic dilated cardiomyopathy

Ventricular tachycardia (VT) and VF account for the majority of sudden cardiac deaths worldwide. Treatments for VT/VF include anti-arrhythmic drugs, ICDs and catheter ablation, but these treatments vary in effectiveness and carry substantial risks and/or expense. Current methods of selecting patients for ICD implantation are imprecise and fail to identify some at-risk patients, while leading to others being overtreated. In this article, the authors discuss the current role and future direction of cardiac MRI (CMRI) in refining diagnosis and personalising ventricular arrhythmia management. The capability of CMRI with gadolinium contrast delayed-enhancement patterns and, more recently, T1 mapping to determine the aetiology of patients presenting with heart failure is well established. Although CMRI imaging in patients with ICDs can be challenging, recent technical developments have started to overcome this. CMRI can contribute to risk stratification, with precise and reproducible assessment of ejection fraction, quantification of scar and ‘border zone’ volumes, and other indices. Detailed tissue characterisation has begun to enable creation of personalised computer models to predict an individual patient’s arrhythmia risk. When patients require VT ablation, a substrate-based approach is frequently employed as haemodynamic instability may limit electrophysiological activation mapping. Beyond accurate localisation of substrate, CMRI could be used to predict the location of re-entrant circuits within the scar to guide ablation

Design and clinical validation of novel imaging strategies for analysis of arrhythmogenic substrate

_CURRENT CHALLENGES IN ELECTROPHYSIOLOGY_ Technical advances in cardiovascular electrophysiology have resulted in an increasing number of catheter ablation procedures reaching 200 000 in Europe for the year 2013. These advanced interventions are often complex and time consuming and may cause significant radiation exposure. Furthermore, a substantial number of ablation procedures remain associated with poor (initial) outcomes and frequently require ≥1 redo procedures. Innovations in modalities for substrate imaging could facilitate our understanding of the arrhythmogenic substrate, improve the design of patient-specific ablation strategies and improve the results of ablation procedures. _NOVEL SUBSTRATE IMAGING MODALITIES_ __Cardiac magnetic resonance__ Cardiac magnetic resonance imaging (CMR) can be considered the most comprehensive and suitable modality for the complete electrophysiology and catheter ablation workup (including patient selection, procedural guidance, and [procedural] follow-up). Utilizing inversion recovery CMR, fibrotic myocardium can be visualized and quantified 10–15 min after intravenous administration of Gadolinium contrast. This imaging technique is known as late Gadolinium enhancement (LGE) imaging. Experimental models have shown excellent agreement between size and shape in LGE CMR and areas of myocardial infarction by histopathology. Recent studies have also demonstrated how scar size, shape and location from pre-procedural LGE can be useful in guiding ventricular tachycardia’s (VT) ablation or atrial fibrillation (AF) ablation. These procedures are often time-consuming due to the preceding electrophysiological mapping study required to identify slow conduction zones involved in re-entry circuits. Post-processed LGE images provide scar maps, which could be integrated with electroanatomic mapping systems to facilitate these procedures. __Inverse potential mapping__ Through the years, various noninvasive electrocardiographic imaging techniques have emerged that estimate epicardial potentials or myocardial activation times from potentials recorded on the thorax. Utilizing an inverse procedure, the potentials on the heart surface or activation times of the myocardium are estimated with the recorded body surface potentials as source data. Although this procedure only estimates the time course of unipolar epicardial electrograms, several studies have demonstrated that the epicardial potentials and electrograms provide substantial information about intramyocardial activity and have great potential to facilitate risk-stratification and generate personalized ablation strategies. __Objectives of this thesis__ 1. To evaluate the utility of cardiac magnetic resonance derived geometrical and tissue characteristic information for patient stratification and guidance of AF ablation. 2. To design and evaluate the performance of a finite element model based inverse potential mapping in predicting the arrhythmogenic focus in idiopathic ventricular tachycardia using invasive electro-anatomical activation mapping as a reference standard

Contemporary Management of Complex Ventricular Arrhythmias

Percutaneous catheter ablation is an effective and safe therapy that can eliminate ventricular tachycardia, reducing the risks of both recurrent arrhythmia and shock therapies from a defibrillator. Successful ablation requires accurate identification of arrhythmic substrate and the effective delivery of energy to the targeted tissue. A thorough pre-procedural assessment is needed before considered 3D electroanatomical mapping can be performed. In contemporary practice, this must combine traditional electrophysiological techniques, such as activation and entrainment mapping, with more novel physiological mapping techniques for which there is an ever-increasing evidence base. Novel techniques to maximise energy delivery to the tissue must also be considered and balanced against their associated risks of complication. This review provides a comprehensive appraisal of contemporary practice and the evidence base that supports recent developments in mapping and ablation, while also considering potential future developments in the field

Contemporary Management of Complex Ventricular Arrhythmias

Percutaneous catheter ablation is an effective and safe therapy that can eliminate ventricular tachycardia, reducing the risks of both recurrent arrhythmia and shock therapies from a defibrillator. Successful ablation requires accurate identification of arrhythmic substrate and the effective delivery of energy to the targeted tissue. A thorough pre-procedural assessment is needed before considered 3D electroanatomical mapping can be performed. In contemporary practice, this must combine traditional electrophysiological techniques, such as activation and entrainment mapping, with more novel physiological mapping techniques for which there is an ever-increasing evidence base. Novel techniques to maximise energy delivery to the tissue must also be considered and balanced against their associated risks of complication. This review provides a comprehensive appraisal of contemporary practice and the evidence base that supports recent developments in mapping and ablation, while also considering potential future developments in the field

Understanding ventricular tachycardia : towards individualized substrate-based therapy

Patients with structural heart disease - e.g. after myocardial infarction or due to a cardiomyopathy - are at increased risk for sudden cardiac death because of arrhythmia. The department of Cardiology at the Leiden University Medical Center has a strong interest for the underlying substrate and mechanisms of ventricular arrhythmias. Since 2011, research fellow Sebastiaan Piers and his supervisor prof. dr. Katja Zeppenfeld have performed innovative studies, combining advanced electrophysiological data with detailed imaging data derived from CT and MRI. These studies have led to important insights into the substrate and mechanisms of ventricular arrhythmia in patients after myocardial infarction or with a cardiomyopathy. An improved understanding may be the most important prerequisite for the development of effective, individualized and substrate-based therapies for ventricular arrhythmias in the future. Sebastiaan Piers will defend his thesis "Understanding Ventricular Tachycardia: Towards Individualized Substrate-based Therapy" on Thursday January 28th 2016.The printing of this thesis was financially supported by St. Jude Medical, Biotronik, Bayer HealthCare, Sanofi Aventis, Chipsoft, Medis Medical Imaging and Toshiba Medical Systems. Het verschijnen van dit proefschrift werd mede mogelijk gemaakt door de steun van de Nederlandse Hartstichting en de Stichting Wetenschap en Onderzoek Interne Geneeskunde Onze Lieve Vrouwe Gasthuis.UBL - phd migration 201

Electrophysiologic Characterization of the Arrhythmogenic Substrate in Reentrant Atrial and Ventricular Arrhythmias Insights from the Clinical and Experimental Electrophysiology Laboratories

This thesis encompasses an overview and critical analysis of 11 publications of clinical and translational cardiac electrophysiology research that has been executed over the last seven years. The focus of this dissertation and the selected papers is on the use of electroanatomic mapping technology to define the arrhythmogenic substrate in patients with structural heart disease and ventricular arrhythmias. Such advancements in elucidating the mechanisms and pathophysiology underlying scar-related ventricular tachycardia have yielded improved clinical outcomes for patients with drug-refractory ventricular arrhythmias. Chapter 1 describes the epidemiologic background and introduces the concept of intracardiac mapping and the technological evolution that has provided the basis for this current body of work. Chapter 2 and Chapter 3 provide a detailed description of how electroanatomic mapping studies have provided critical insight into disease pathogenesis in patients with dilated nonischemic cardiomyopathy arrhythmogenic right ventricular cardiomyopathy (ARVC). The clinical impact and relevance of these studies are discussed based on conventional electroanatomic mapping technologies to define abnormal physiological substrates. Chapter 3 also addresses important considerations regarding percutaneous epicardial mapping and ablation that have been derived from extensive clinical experience. Chapter 4 and Chapter 5 describe the evolution of mapping technologies and the use of high-resolution mapping system technologies. These chapters discuss the potential clinical advantages of these technologies during substrate and activation mapping, particularly in post-infarct ventricular scar and VT. Finally, Chapter 6 concludes this thesis with final thoughts on the broader context of the lessons that have been learned from the studies that are presented in this thesis and implications for future work

2019 HRS/EHRA/APHRS/LAHRS Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias: Executive summary

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. An expert writing group, after reviewing and discussing the literature, including a systematic review and meta-analysis published in conjunction with this document, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Each recommendation is presented in knowledge byte format and is accompanied by supportive text and references. Further sections provide a practical synopsis of the various techniques and of the specific ventricular arrhythmia sites and substrates encountered in the electrophysiology lab. The purpose of this document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias

FDG-PET Imaging in Cardiac Sarcoidosis : Importance of the pathological findings in the right ventricle

Sarkoidoosi on tulehdussairaus joka voi esiintyä missä elimessä tahansa. Yleisimmin se ilmenee keuhkoissa ja välikarsinan imusolmukkeissa. Sarkoidoosi on usein oireeton sattumalöydös ja sen ennuste on suotuisa. Sarkoidoosi voi kuitenkin esiintyä sydänlihaksessa jopa neljänneksessä tapauksista. Sydämessä esiintyvään tautimuotoon liittyy merkittävää sairastavuutta ja kuolleisuutta. FDG-PET on isotooppitutkimus, jolla voidaan kuvata elimistön metabolista aktiivisuutta ja osoittaa muun muassa tulehdusprosessiin liittyvää korostunutta sokeriaineenvaihduntaa. Tätä väitöskirjatutkimusta varten uudelleenanalysoitiin 137 tehtyä FDG-PET tutkimusta, jotka oli tehty elokuun Tampereen yliopistosairaalassa elokuun 2012 ja syyskuun 2015 välillä sydänsarkoidoosiepäilyn vuoksi. Halusimme tutkia PET- kuvauksen merkitystä potilailla, joilla epäiltiin sydämen sarkoidoosia. Vertasimme PET-löydöksiä potilaiden perustietoihin, sairaushistoriaan ja EKG-löydöksiin. Lisäksi tutkimme sydämen ja sydämen ulkopuolisten poikkeavien aineenvaihduntafokusten suhdetta ja selvitimme PET-löydösten kykyä ennustaa sydäntapahtumia. Havaitsimme, että poikkeavia sydänlöydöksiä oli enemmän naisilla ja niillä joilla oli sairaushistoriassa merkintä eteis-kammiokatkoksesta. Oikean kammion poikkeavia muutoksia oli useammin potilailla, joilla oli ollut kammioperäisiä rytmihäiriöitä. Poikkeavat sydänlöydökset olivat yleisempiä potilailla, joiden EKG:ssa oli nähtävissä QRS-kompleksin fragmentaatiota useissa kytkennöissä, oikean etuhaarakkeen katkos. Poikkeavat sydämen PET-löydökset liittyivät myös väliseinän uudelleenmuovautumiseksi ja alaseinän uudelleenmuovautumiseksi nimettyihin, hiljattain määriteltyihin EKG-muuttujiin. Sarkoidoosiin sopiva kudosnäyte saatiin useammin potilailta, joilla nähtiin aineenvaihduntafokuksia sydämen ulkopuolella. Sydämen ulkopuolisilla ja oikean kammion poikkeavilla PET-löydöksillä havaittiin olevan yhteys. Oikean kammion poikkeavat löydökset ja korkea sydämen kokonaisaineenvaihdunta-aktiivisuus ennustivat sydäntapahtumia. Tulosten perusteella FDG-PET on käyttökelpoinen tutkimus sydänsarkoidoosiepäilyssä. Tunnistimme potilasryhmiä, joilla poikkeavan PET- löydöksen todennäköisyys on korkea. Havaitsimme, että PET-tutkimus voi osoittaa kohteita kudosnäytteen ottoon ja auttaa siten diagnoosiin pääsyssä. Lisäksi havaitsimme tiettyjen PET-löydösten liittyvän suureen sydäntapahtumien riskiin, mikä tulee ottaa huomioon potilaan hoidossa.Sarcoidosis is a granulomatous inflammatory disease that can affect any organ system. It most often manifests in lungs and hilar lymph nodes. It is often asymptomatic and has a benign prognosis. With a quarter of the patients, sarcoid inflammation affects the heart and this cardiac involvement accounts for the majority of sarcoidosis-related morbidity and mortality. FDG-PET is a nuclear medicine imaging study with an ability to visualize inflammatory foci. Lately, it has gained importance in the workup of cardiac sarcoidosis. One hundred thirty-seven PET studies performed in Tampere University Hospital between August 2012 and September 2015 for patients suspected with cardiac sarcoidosis were retrospectively analysed. With an aim to study the role of FDG- PET in the workup of cardiac sarcoidosis, we examined the associations of PET- findings and patient characteristics, PET-findings and ECG-parameters and the association of PET-findings in the heart and metabolically active foci elsewhere in the body. In addition, we assessed the prognostic role of PET. Pathological cardiac PET-findings were found to be more frequent in female patients and with those with a history of atrioventricular block. Right ventricular uptake was also associated with a history of ventricular tachycardia. Pathological cardiac PET findings also correlated to novel ECG parameters septal remodelling and inferolateral remodelling in addition to widespread QRS fragmentation and left anterior hemiblock. A biopsy sample indicating sarcoidosis was obtained more frequently from patients with metabolically active foci outside of the heart. Additionally, an association between right ventricular uptake and uptake in mediastinal and hilar lymph nodes was observed. In our population, right ventricular uptake and high total cardiac metabolic activity predicted adverse cardiac events during follow-up. Our study identified a group of patients, defined according to sex, medical history and certain ECG parameters, who have a higher frequency of positive cardiac findings in FDG-PET. The imaging study can be a useful tool in the workup of cardiac sarcoidosis as it can aid in the diagnosis by pointing targets for tissue biopsy. Furthermore, certain findings could be considered as indicators for high risk of cardiac events