A novel simplified approach to radiofrequency catheter ablation of idiopathic ventricular outflow tract premature ventricular contractions : from substrate analysis to results

Summary: Premature ventricular contractions (PVCs) are a common finding in the general population. The most common site of PVCs, in patients without structural heart disease, is the right ventricular outflow tract (RVOT) and the left ventricular outflow tract (LVOT). The prognosis associated with frequent PVCs depends on the presence of structural heart disease, so that idiopathic PVCs have been considered benign. Recently however, evidence has emerged that a small percentage of those patients may present with polymorphic ventricular tachycardia or ventricular fibrillation or evolve to left ventricular dysfunction. Catheter ablation is indicated for frequent symptomatic PVCs refractory to medical therapy or in case of patient’s preference. Currently, catheter ablation is based on activation mapping, confirmed by pace mapping match of at least 11/12 ECG leads between the paced beat and the PVC morphology. The acute success rate ranges from 78% to 100% according to the series, and to the location of the PVCs. Remote magnetic navigation presents as a good option for PVC ablation offering a high success rate with better safety profile. Intraprocedural low PVC burden occurs in up to 30% to 48% of cases, resulting in either, cancelation of the ablation procedure in up to 11% of patients, or reduction of the success rate from 85% to 56% when ablation is attempted with pace mapping only. Recently non-invasive mapping systems based on the electrocardiogram analysis (ECGI) have been developed. These systems are capable of mapping an arrhythmia with just one beat, instead of the usual point by point acquisition, being especially useful in the case of rare arrhythmias. EGGI also constitutes a valuable noninvasive tool for studying the mechanisms of arrhythmias. With this system we were able to demonstrate the presence of an electrophysiological substrate in the RVOT of patients with PVCs and apparently normal hearts. It has been accepted for many years that in patients with idiopathic PVCs from the outflow tracts, the RVOT displays normal electroanatomical mapping features and electrophysiological properties. However, we have demonstrated that there is a substrate for idiopathic PVCs in the form of low voltage areas (LVAs) that are not detected by usual image methods including cardiac magnetic resonance (CMR). We described for the first time, the association between the presence of ST-segment elevation in V1-V2 at the 2nd intercostal space (ICS) with LVAs across the RVOT and have proposed it as a non-invasive electrocardiographic marker of LVAs. We also identified the presence of abnormal potentials in intracardiac electrograms at the ablation site during diastole, after the T wave of the surface ECG that became presystolic during the PVC and were called diastolic potentials (DPs). In Chapter V we describe in detail the study that validated those findings and evaluated the feasibility and efficacy of a proposed simplified substrate approach, for catheter ablation in patients with low intraprocedural PVC burden, defined as less than 2 PVCs/min in the first 5 minutes of the procedure. It consists of fast mapping of the RVOT in sinus rhythm looking for LVAs and DPs, identifying the area, and finally performing a restricted activation map of the PVCs at that area. Briefly, it was a prospective single-arm clinical trial at two centers and three groups were studied: a) patients with low intraprocedural PVC burden that underwent ablation with the novel simplified approach method (study group); b) patients with low intraprocedural PVC burden that underwent ablation using the standard activation mapping method between 2016 and 2018 (historical group); and c) patients without PVCs, subjected to catheter ablation of supraventricular tachycardias that agreed to have a voltage map of the RVOT in sinus rhythm performed (validation group). The calculated sample size was 38 patients in each group. The exclusion criteria were as follows: known structural heart disease, history of sustained ventricular arrhythmias, inability to perform CMR, previous ablation and standard 12-Lead ECG with evidence of conduction or electrical disease or abnormal QRS morphology were excluded. Patients in the study and validation groups, had an ECG performed at the 2nd ICS and the RVOT mapped in sinus rhythm to assess the presence of ST-segment elevation, and LVAS and DPs, respectively. The results were compared between both groups. The study group and the historical group were compared regarding the efficacy of the new simplified ablation method in terms of abolishment of the PVCs and improvement of procedure speed and success rate. When available, ECGI was performed in the study group to evaluate the accuracy of the method to identify the site of origin of the PVCs. The ECGI was performed with two systems, the Amycard (EP Solutions SA, Switzerland) and the VIVO (Catheter Precision, NJ USA). The prevalence of LVAs and DPs was significantly higher in the study group in comparison with the validation group, respectively, 71% vs 11%, p<0.0001 and 87% vs 8%, p<0.0001. The ST-segment elevation was a good predictor of LVAS with a sensitivity of 87%, specificity of 96%, positive predictor value of 93% and negative predictor value of 91%. The novel simplified approach abolished the PVCs in 90% of the patients as opposed to 47% of patients in the historical group, p<0.0001. Only 74% patients underwent ablation in the historical group versus 100% in the study group. In patients that underwent ablation, the procedure time was significantly lower in the study group when comparing to the historical group, 130 (100-164) vs 183 (160-203) min, p<0.0001 and the success rate was significantly higher, 90% vs 64%, p=0.013. The recurrence rate in patients with a successful ablation after a median follow-up time of 1060 (574-1807) days, was not significantly different between both groups, Log-Rank=0.125 ECGI before ablation was performed in 17 patients in the study group. In 6 patients the ECGI was performed just with the Amycard system, in two just with the VIVO system and in 9 patients both systems were used. We found a good agreement between the ECGI and the invasive mapping, with the predicted site of origin being in the same or contiguous segment of the ablation site in 14/15 patients (93%) with the Amycard system and in 100% of patients with the VIVO system. When both systems were used simultaneously, the agreement between them was 8/9 (90%). So, in conclusion, the proposed approach partially based on substrate mapping including searching for LVAs and DPs, proved to be feasible, faster, and more efficient than the previous approach based exclusively on activation mapping. ST-segment elevation at the 2nd ICS proved to be a good predictor of LVAs. ECGI was a valuable tool to noninvasively predict the site of origin the arrhythmia

Prospect of clinical application of ECG imaging technology

Routine 12 lead ECG is a basic method for clinical evaluation and diagnosis of various cardiovascular diseases. However, due to its low accuracy of ECG mapping, it is seriously limited in the study of potential electrophysiological mechanism of arrhythmia and mapping of origin matrix. The emerging non-invasive ECG imaging technology (ECGI) can reverse reconstruct the spatio-temporal dynamic information of electrophysiological activities at various locations of the heart, explore the occurrence and development mechanism of various arrhythmias, and accurately locate their origin, effectively make up for the lack of traditional mapping technology, and play a very important role in guiding clinical diagnosis and treatment. In recent years, studies at home and abroad have shown that ECGI plays an important role in the diagnosis and treatment of various cardiovascular diseases, such as arrhythmias and cardiac resynchronization therapy. As a non-invasive method, three-dimensional ECGI is a significant progress in conventional ECG mapping, and its great potential to guide clinical diagnosis and treatment needs to be tapped. This article reviews the progress of clinical application of ECGI

Evaluation and treatment of premature ventricular contractions in heart failure with reduced ejection fraction

Premature ventricular complexes (PVCs) are often observed in patients presenting with heart failure with a reduced ejection fraction (HFrEF). PVCs may in some patients be considered to be the cause of heart failure, while in others it may be the consequence of heart failure. PVCs are important prognostic markers in HFrEF. The uncertainty whether PVCs are the cause or effect in HFrEF impacts clinical decision making. In this review, we discuss the complexity of the cause-effect relationship between PVCs and HFrEF. We demonstrate a workflow with the use of a trial period of amiodarone that may discover whether the reduced LVEF is reversible, the symptoms are due to PVCs and whether biventricular pacing can be increased by the reduction of PVCs. The use of non-invasive and invasive (high-density) mapping techniques may help to improve accuracy and efficacy in the treatment of PVC, which will be demonstrated. With these results in mind, we conclude this review highlighting the future directions for PVC research and treatment

Electrocardiographic algorithms to guide a management strategy of idiopathic outflow tract ventricular arrhythmias

The current guidelines of the European Society of Cardiology outlined electrocardiographic (ECG) differentiation of the site of origin (SoO) in patients with idiopathic ventricular arrhythmias (IVAs). The aim of this study was to compare 3 ECG algorithms for differentiating the SoO and to determine their diagnostic value for the management of outflow tract IVA. We analyzed 202 patients (mean age [SD]: 45 [16.7] years; 133 women [66%]) with IVAs with the inferior axis (130 premature ventricular contractions or ventricular tachycardias from the right ventricular outflow tract [RVOT]; 72, from the left ventricular outflow tract [LVOT]), who underwent successful radiofrequency catheter ablation (RFCA) using the 3‑dimensional electroanatomical system. The ECGs before ablation were analyzed using custom‑developed software. Automated measurements were performed for the 3 algorithms: 1) novel transitional zone (TZ) index, 2) $V_{2}S/V_{3}R$, and 3) $V_{2}$ transition ratio. The results were compared with the SoO of acutely successful RFCA. The $V_{2}S/V_{3}R$ algorithm predicted the left‑sided SoO with a sensitivity and specificity close to 90%. The TZ index showed higher sensitivity (93%) with lower specificity (85%). In the subgroup with the transition zone in lead V3 (n = 44, 15 from the LVOT) the sensitivity and specificity of the V2– transition‑ratio algorithm were 100% and 45%, respectively. The combined TZ index+$V_{2}S/V_{3}R$ algorithm (LVOT was considered only when both algorithms suggested the LVOT SoO) can increase the specificity of the LVOT SoO prediction to 98% with a sensitivity of 88%. The combined TZ‑index and $V_{2}S/V_{3}R$ algorithm allowed an accurate and simple identification of the SoO of IVA. A prospective study is needed to determine the strategy for skipping the RVOT mapping in patients with LVOT arrhythmias indicated by the 2 combined algorithms

Evaluation and prognostic significance of premature ventricular contractions in patients without structural heart disease

Introduction: Premature ventricular contractions (PVCs) are a common form of arrhythmia associated with poor prognosis in patients with structural heart disease. However, their prognostic impact on healthy individuals is unclear. There is also a lack of evidence about risk stratification of this group through cardiac imaging and electrocardiographic features. With this project we wanted to study whether patients with PVCs in which structural heart disease had thoroughly been excluded, have a worse prognosis than a control population. Moreover, we wanted to investigate whether PVC morphology and/or PVC duration are associated with the clinical outcome. Finally, we explored whether cardiac magnetic resonance imaging (CMR) and advanced echocardiographic parameters could unmask signs of structural heart disease in patients with high PVC-burden and normal echocardiogram. Methods: To study the prognostic impact of PVCs, we identified 807 patients with no history of structural heart disease, normal echocardiography and exercise test and verified PVCs. During a follow-up period of 5.2 years, we compared the clinical outcome–in terms of total mortality and cardiovascular morbidity–with a population matched by sex and age. To explore whether electrocardiographic features have a prognostic significance among healthy PVC-patients, we identified 541 patients to which we had access to PVC recording on 12-lead ECG and analysed PVC morphology and QRS width. For the studies focusing on diagnostic evaluation through advanced cardiac imaging, we included patients with a PVC burden of at least 10,000 beats/day and with normal results at exercise test and echocardiography. They underwent additional investigation with CMR (study 2) or advanced echocardiographic parameters that are normally not included in clinical praxis (study 3). Results: Healthy PVC-patients had a generally favourable prognosis, showing no worse clinical outcome than the sex- and age-matched control group that had not undergone investigation to rule out heart disease. However, patients with high PVC-burden showed signs of myocardial dysfunction when advanced imaging techniques were used, despite normal results at standard investigation that included echocardiogram. Sub-group analysis based on PVC-morphology showed that PVC originating from the outflow tract and the right ventricle was associated with a more favourable prognosis than intra cavity- and left ventricular PVCs respectively. Analysis of PVC-duration– measured as QRS-width during PVC–showed no impact on clinical outcome. Conclusions: PVC patients who had undergone a thorough medical examination with normal results did not have a worse outcome than matched controls during a median follow-up time of 5.2 years. PVC duration did not seem to be associated with the clinical outcome in our study including 541 patients with different sites of origin. However, PVCs with a morphology originating from the outflow tract and the right ventricle were associated with a better outcome. CMR and comprehensive advanced echocardiography could identify signs of myocardial dysfunction in patients with high PVC burden and normal findings at standard echocardiography. The clinical significance of these imaging findings needs to be assessed by larger longitudinal studies

Integrated whole-heart computational workflow for inverse potential mapping and personalized simulations

Background: Integration of whole-heart activation simulations and inverse potential mapping (IPM) could benefit the guidance and planning of electrophysiological procedures. Routine clinical application requires a fast and adaptable workflow. These requirements limit clinical translation of existing simulation models. This study proposes a comprehensive finite element model (FEM) based whole-heart computational workflow suitable for IPM and simulations. Methods: Three volunteers and eight patients with premature ventricular contractions underwent body surface potential (BSP) acquisition followed by a cardiac MRI (CMR) scan. The cardiac volumes were segmented from the CMR images using custom written software. The feasibility to integrate tissue-characteristics was assessed by generating meshes with virtual edema and scar. Isochronal activation maps were constructed by identifying the fastest route through the cardiac volume using the Möller-Trumbore and Floyd-Warshall algorithms. IPM's were reconstructed from the BSP's. Results: Whole-heart computational meshes were generated within seconds. The first point of atrial activation on IPM was located near the crista terminalis of the superior vena cave into the right atrium. The IPM demonstrated the ventricular epicardial breakthrough at the attachment of the moderator band with the right ventricular free wall. Simulations of sinus rhythm were successfully performed. The conduction through the virtual edema and scar meshes demonstrated delayed activation or a complete conductional block respectively. Conclusion: The proposed FEM based whole-heart computational workflow offers an integrated platform for cardiac electrical assessment using simulations and IPM. This workflow can incorporate patient-specific electrical parameters, perform whole-heart cardiac activation simulations and accurately reconstruct cardiac activation sequences from BSP's

Non-compacted cardiomyopathy: clinical-echocardiographic study

The aim of the present study was to describe the clinical and echocardiographic findings of ventricular noncompaction in adult patients. Fifty-three patients underwent complete clinical history, electrocardiogram, Holter and transthoracic echocardiogram. Forty patients (75%) were in class I/II of the New York Heart Association, and 13 (25%) in class III/IV. Ventricular and supraventricular escape beats were found in 40% and 26.4%, respectively. Holter showed premature ventricular contractions in 32% and sustained ventricular tachycardia in 7.5%. Ventricular noncompaction was an isolated finding in 74% of cases and was associated with other congenital heart disease in 26%. Noncompacted ventricular myocardium involved only left ventricle in 62% of the patients and both ventricles in 38%. The mean ratio of noncompacted to compacted myocardial layers at the site of maximal wall thickness was 3.4 ± 0.87 mm (range 2.2–7.5). The presence of ventricular noncompaction in more than three segments was associated with a functional class greater than II and ventricular arrhythmia with demonstrable statistical significance by χ(2)(p < 0.003). CONCLUSION: a) Noncompacted cardiomyopathy is a congenital pathological entity that can occur in isolated form or associated with other heart disease and often involves both ventricles. b) A ratio of noncompacted to compacted myocardium greater than 3 and involvement of three or more segments are indicators of poor prognosis. c) Since the clinical manifestations are not sufficient to establish diagnosis, echocardiography is the diagnostic tool that makes it possible to document ventricular noncompaction and establish prognostic factors

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

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