Practical guidance and clinical applications of transoesophageal echocardiography. A position paper of the working group of echocardiography of the Hellenic Society of Cardiology.

Transoesophageal echocardiography (TOE) is a well-established imaging modality, providing more accurate and of higher quality information than transthoracic echocardiography (TTE) for a wide spectrum cardiac and extra-cardiac diseases. The present paper represents an effort by the Echocardiography Working Group (WG) of the Hellenic Cardiology Society to state the essential steps of the typical TOE exam performed in echo lab. This is an educational text, describing the minimal requirements and the preparation of a meticulous TOE examination. Most importantly, it gives practical instructions to obtain and optimize TOE views and analyses the implementation of a combined two-and multi-dimensional protocol for the imaging of the most common cardiac structures during a TOE. In the second part of the article a comprehensive review of the contemporary use of TOE in a wide spectrum of valvular and non-valvular cardiac diseases is provided, based on the current guidelines and the experience of the WG members.

Application of next generation sequencing in cardiology: current and future precision medicine implications.

Inherited cardiovascular diseases are highly heterogeneous conditions with multiple genetic loci involved. The application of advanced molecular tools, such as Next Generation Sequencing, has facilitated the genetic analysis of these disorders. Accurate analysis and variant identification are required to maximize the quality of the sequencing data. Therefore, the application of NGS for clinical purposes should be limited to laboratories with a high level of technological expertise and resources. In addition, appropriate gene selection and variant interpretation can result in the highest possible diagnostic yield. Implementation of genetics in cardiology is imperative for the accurate diagnosis, prognosis and management of several inherited disorders and could eventually lead to the realization of precision medicine in this field. However, genetic testing should also be accompanied by an appropriate genetic counseling procedure that clarifies the significance of the genetic analysis results for the proband and his family. In this regard, a multidisciplinary collaboration among physicians, geneticists, and bioinformaticians is imperative. In the present review, we address the current state of knowledge regarding genetic analysis strategies employed in the field of cardiogenetics. Variant interpretation and reporting guidelines are explored. Additionally, gene selection procedures are accessed, with a particular emphasis on information concerning gene-disease associations collected from international alliances such as the Gene Curation Coalition (GenCC). In this context, a novel approach to gene categorization is proposed. Moreover, a sub-analysis is conducted on the 1,502,769 variation records with submitted interpretations in the Clinical Variation (ClinVar) database, focusing on cardiology-related genes. Finally, the most recent information on genetic analysis's clinical utility is reviewed.

Right ventricular outflow tract endocardial unipolar substrate mapping: implications in risk stratification of Brugada syndrome.

Brugada syndrome (BrS) is a complex arrhythmogenic disease displaying electrical and micro-structural abnormalities mainly located at the epicardium of the right ventricular outflow tract (RVOT). It is well-known that fibrosis, fatty infiltration, inflammation and reduced gap junction expression have been demonstrated at the epicardial anterior aspect of the RVOT providing the arrhythmogenic substrate for ventricular arrhythmic events in BrS. A number of models have been proposed for the risk stratification of patients with BrS. Endocardial unipolar electroanatomical mapping is an emerging tool that has been reintroduced to identify and quantify epicardial electrical abnormalities. Interestingly, current findings correlate the presence of large-sized endocardial unipolar electroanatomical abnormalities with either ventricular fibrillation inducibility during programmed ventricular stimulation or symptom status. This review aims to present existing data about the role of endocardial unipolar electroanatomical mapping for the identification of RVOT epicardial abnormalities as well as its potential clinical implications in risk stratification of BrS.

Left Atrial Function Post Radiofrequency and Cryoballoon Ablation Assessed by Volume-Pressure Loops.

Background: Left atrial (LA) function is linked to atrial fibrillation (AF) pathogenesis. AF catheter ablation decreases disease burden with potentially favorable effects on cardiac function. Atrial volume-pressure loops can optimally assess the LA function. Objective: To investigate changes in LA function by volume-pressure loops after paroxysmal AF ablation and explored potential differences between the radiofrequency and cryoballoon ablation. Methods: We analyzed 44 patients undergoing paroxysmal AF ablation from 2 centers, 22 treated with radiofrequency and 22 with cryoablation. Pre- and post-procedure, all patients underwent a real-time three-dimensional transthoracic ECG to evaluate LA volume, while simultaneously recording LA pressure following transseptal puncture. Volume-pressure loops pre- and post-procedure were created by paired data. Areas of A-loop (LA booster pump function) and V-loop (LA reservoir function), and the stiffness constant determining the slope of the exponential curve during LA filling were calculated. Results: Average LA pressure, A-wave amplitude, and V-wave amplitude were increased post-procedurally (p < 0.001). Overall, A-loop area decreased (p = 0.001) and V-loop area tended to increase (p = 0.07). The change in both A-loop and V-loop areas was similar between radiofrequency- and cryoballoon-treated patients (p = 0.18 and p = 0.52, respectively). However, compared with cryoballoon-treated patients, radiofrequency-treated patients had higher increase in the stiffness constant (b = 0.059; 95% CI: 0.022-0.096; p = 0.006). Conclusion: AF catheter ablation by the radiofrequency or cryoballoon is associated with the decrease of the booster pump function and increase of the reservoir function. Moreover, there is a post-procedural increase of LA pressure which is associated with an acute increase in LA stiffness in radiofrequency ablation, but not in cryoablation.

Right ventricular outflow tract electroanatomical abnormalities in asymptomatic and high-risk symptomatic patients with Brugada syndrome: Evidence for a new risk stratification tool?

INTRODUCTION: Microstructural abnormalities at the epicardium of the right ventricular outflow tract (RVOT) may provide the arrhythmia substrate in Brugada syndrome (BrS). Endocardial unipolar electroanatomical mapping allows the identification of epicardial abnormalities. We evaluated the clinical implications of an abnormal endocardial substrate as perceived by high-density electroanatomical mapping (HDEAM) in patients with BrS. METHODS: Fourteen high-risk BrS patients with aborted sudden cardiac death (SCD) (12 males, mean age: 41.9 ± 11.8 years) underwent combined endocardial-epicardial HDEAM of the right ventricle/RVOT, while 40 asymptomatic patients (33 males, mean age: 42 ± 10.7 years) underwent endocardial HDEAM. Based on combined endocardial-epicardial procedures, endocardial HDEAM was considered abnormal in the presence of low voltage areas (LVAs) more than 1 cm2 with bipolar signals less than 1 mV and unipolar signals less than 5.3 mV. Programmed ventricular stimulation (PVS) was performed in all patients. RESULTS: The endocardial unipolar LVAs were colocalized with epicardial bipolar LVAs (p = .0027). Patients with aborted SCD exhibited significantly wider endocardial unipolar (p < .01) and bipolar LVAs (p < .01) compared with asymptomatic individuals. A substrate size of unipolar LVAs more than 14.5 cm2 (area under the curve [AUC]: 0.92, p < .001] and bipolar LVAs more than 3.68 cm2 (AUC: 0.82, p = .001) distinguished symptomatic from asymptomatic patients. Patients with ventricular fibrillation inducibility (23/54) demonstrated broader endocardial unipolar (p < .001) and bipolar LVAs (p < .001) than noninducible patients. The presence of unipolar LVAs more than 13.5 cm2 (AUC: 0.95, p < .001) and bipolar LVAs more than 2.97 cm2 (AUC: 0.78, p < .001) predicted a positive PVS. CONCLUSION: Extensive endocardial electroanatomical abnormalities identify high-risk patients with BrS. Endocardial HDEAM may allow risk stratification of asymptomatic patients referred for PVS.

Atrial substrate characterization in patients with atrial fibrillation and hypertrophic cardiomyopathy: Evidence for an extensive fibrotic disease.

INTRODUCTION: Data regarding the left atrial (LA) electroanatomical substrate in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) are missing. In this electroanatomical mapping (EAM) study, we evaluated the extent of LA fibrosis and its impact on catheter ablation outcomes in patients with HCM and AF. MATERIALS AND METHODS: High-density LA EAM was performed during AF in 28 consecutive patients with obstructive HCM and AF (42.9% displayed paroxysmal AF and 57.1% persistent AF). Propensity score (PS) matching analysis was performed to reduce the impact of potential confounding factors. PS were derived to match patients at a 1:1 ratio. Patients were matched according to age, sex and LA diameter. After PS, 28 non-HCM patients with AF were selected, and served as controls. Two different cut-off values of bipolar signal amplitude were investigated for fibrosis characterization (≤0.25 mV and ≤ 0.4 mV). HCM patients underwent pulmonary vein antral isolation (PVAI) and roof line, while non-HCM patients PVAI only. RESULTS: After the 3-month blanking period, 10 HCM patients (35.7%) displayed atrial arrhythmia recurrence. HCM patients with arrhythmia recurrence showed significantly greater low voltage areas defined as either bipolar voltage ≤0.25 mV (22.5 ± 10% vs. 5.5 ± 6.4%, p = 0.001) or ≤ 0.4 mV (32 ± 13.9% vs. 5.9 ± 5.1%, p < 0.001). The presence of low voltage areas ≤0.4 mV greater than 14.1% of the total LA area also predicted arrhythmia recurrence with excellent sensitivity (100%) and specificity (100%). Univariate analysis revealed that the extent of LA fibrosis was the only predictor of AF recurrence. After PS matching with non-HCM patients, patients with HCM exhibited wider fibrotic regions ≤0.25 mV compared to non-HCM patients (p = 0.016). CONCLUSIONS: High-density EAM reveals extensive LA fibrotic disease in patients with HCM, an event with certain implications in catheter ablation outcomes.

RBM20 mutation and ventricular arrhythmias in a young patient with dilated cardiomyopathy: a case report.

Gene mutations in RBM20 have been identified in a minority of familial and sporadic dilated cardiomyopathy cases. Recent studies of carriers of RBM20 mutations not only highlight the aforementioned association with dilated cardiomyopathy but also indicate a link with increased incidence of ventricular arrhythmias. Herein we describe a case of 17-year-old female patient with dilated cardiomyopathy carrying a p.(Arg634Trp) RBM20 mutation and presenting with frequent premature ventricular contractions and episodes of non-sustained ventricular tachycardia.

Safety of catheter ablation of atrial fibrillation without pre- or peri-procedural imaging for the detection of left atrial thrombus in the era of uninterrupted anticoagulation.

BACKGROUND: The need for pre- or peri-procedural imaging to rule out the presence of left atrial thrombus in patients undergoing catheter ablation of atrial fibrillation (AF) is unclear in the era of uninterrupted direct oral anticoagulant (DOAC) regimen. We sought to examine the safety of catheter ablation in appropriately selected patients with paroxysmal AF without performing screening for left atrial thrombus. PATIENTS AND METHODS: Consecutive patients planned for radiofrequency AF catheter ablation between January 2016 and June 2020 were enrolled, and prospectively studied. All subjects were receiving uninterrupted anticoagulation with DOACs for at least 4 weeks before the procedure. All subjects were in sinus rhythm the day of the procedure. The primary outcome of the study was ischemic stroke or transient ischemic attack (TIA) during at 30 days. RESULTS: A total of 451 patients (age 59.7 ± 10.2 years, 289 males) with paroxysmal AF were included in the study. The mean CHA2DS2-VASc score was 1.4 ± 1.2. The mean left ventricular ejection fraction and left atrial diameter were 60 ± 5% and 39.3 ± 4 mm, respectively. Regarding the anticoagulation regimen, apixaban was used in 197 (43.6%) patients, rivaroxaban in 148 (32.8%) patients, and dabigatran in 106 (23.5%) patients. None of the patients developed clinical ischemic stroke or TIA during the 30-day post-discharged period. CONCLUSIONS: Catheter ablation can be safely performed in low-risk patients with paroxysmal AF without imaging for the detection of left atrial thrombus in the era of uninterrupted DOAC anticoagulation.

KCNE2 gene mutation and Brugada syndrome.

KCNE2 gene mutations have been associated with atrial fibrillation, long QT syndrome, Brugada syndrome and unexplained sudden cardiac death. Herein, we describe a case of Brugada syndrome carrying an heterozygous variant in the KCNE2 gene [NM_172201.2:c.161 T > C, p.(Met54Thr, M54T)]. Gain of function of the Ito current possibly explains the Brugada ECG phenotype in this case.

Electrophysiologic study and catheter ablation of a supraventricular tachycardia in a patient with inferior vena cava congenital anomaly.

Electrophysiologic procedures are performed widely nowdays, for the successful treatment of several cardiac arrhythmias. In this case report, we describe a rare congenital anomaly of the inferior vena cava, as an incidental finding during a scheduled electrophysiologic procedure for a supraventricular tachycardia ablation. The patient is a 32 year old male with an unremarkable medical history, suffering from sustained episodes of paroxysmal tachycardia. The electrophysiological maneuvers confirmed the presence of atrioventricular nodal reentry tachycardia, followed by a successful slow pathway ablation. We provide imaging details and guidance on the successful catheter positioning. In cases like this, the prognosis is excellent, while the follow up of our patient was unremarkable.

The aortic cusps are the predominant successful ablation site of idiopathic outflow-tract ventricular arrhythmias.

BACKGROUND: Data regarding the successful ablation site of idiopathic outflow tract (OT) ventricular arrhythmias (VAs) in the modern era of mapping and ablation are limited. METHODS AND RESULTS: Over a 4-year period, a total of 309 patients underwent detailed activation mapping of OT VAs including the right ventricular outflow tract (RVOT), the left ventricular outflow tract (LVOT) and the aortic cusps (AC), and the coronary venous system. 244 cases were successfully ablated at the index procedure (78.9%). The successful ablation site was more frequently located at the LVOT/ACs (51.6%) followed by RVOT (36.2%). In particular, the ACs was the predominant successful ablation site of idiopathic OT VAs (46.7%). An epicardial site of origin was predictor of ablation failure (p < 0.05). CONCLUSIONS: The ACs is the predominant successful ablation site of idiopathic OT VAs. TAKE-HOME MESSAGE: The aortic cusps are the predominant successful ablation site of idiopathic idiopathic outflow tract ventricular arrhythmias.

A novel variant of RyR2 gene in a family misdiagnosed as congenital long QT syndrome: The importance of genetic testing.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) and Long-QT syndrome (LQTS) are two distinct entities with similar clinical presentation and management but different clinical course. In this study, we present two family members presented with aborted sudden cardiac death (SCD) that was attributed to CPVT. The CPVT may be underrecognized in SCD victims and a diagnosis of "atypical LQTS" may warrant consideration of CPVT and analysis of RyR2 if the standard cardiac channel gene screen for LQTS is negative. Although the management of both channelopathies is quite common the clinical outcomes are different, with CPVT displaying a more malignant clinical course.

Left atrial voltage mapping using a new impedance-based algorithm in patients with paroxysmal atrial fibrillation.

AIMS: Atrial fibrosis is associated with the pathogenesis and progression of atrial fibrillation (AF). We sought to evaluate the extent of left atrial (LA) scarring in patients with paroxysmal AF (PAF) undergoing catheter ablation using a new impedance-based algorithm. METHODS: We prospectively enrolled 73 consecutive patients (43 males, 58 years) with PAF who underwent pulmonary vein antral isolation. We first performed high-density bipolar voltage mapping during sinus rhythm using Tissue Proximity Indicator (TPI), one of the features of the ConfiDense mapping module integrated in the electroanatomic mapping system. A dense LA shell was created initially without TPI (mean points 2,411) and subsequently activating TPI (mean points 1,167). Each point was classified according to the peak-to-peak bipolar voltage electrogram based on two criteria (criterion A: healthy >0.8 mV, border zone: 0.4-0.8 mV, scarred: <0.4 mV; criterion B: healthy: >0.5 mV, border zone: 0.25-0.5 mV, scarred: <0.25 mV). RESULTS: LA voltage analysis represented significantly smaller scarred areas when mapping was performed with TPI-ON compared with TPI-OFF in both voltage criteria (average LA voltage area: 3.02 ± 5.28 cm2 vs 9.15 ± 13.11 cm2 vs in criterion A and 1.19 ± 2.54 cm2 vs 5.61 ± 9.56 cm2 in criterion B). A statistically significant voltage difference was observed in all segments of the left atrium between the two mapping protocols, particularly on the inferior wall. CONCLUSION: A more specific delineation of LA fibrosis may be produced using the TPI feature of the ConfiDense mapping module, through elimination of false-positive annotated mapping points due to low contact.

The perceval S aortic valve implantation in patients with porcelain aorta; is this ideal option?

We would like to present in this paper a patient with severe aortic valve stenosis referred to our department for surgical aortic valve replacement. In this patient, it was intraoperatively detected an unexpected heavily calcified porcelain ascending aorta. We present the treatment options in this situation, the difficulties affronted intraoperatively, the significance of the preoperative chest computed tomography scan and the use of the Perceval S aortic valve as ideal bioprosthesis implantation. This is a self-expanding, self-anchoring, and sutureless valve with a wide indication in all patients requiring aortic bioprosthesis.

Aortic valve replacement in elderly with small aortic root and low body surface area; the Perceval S valve and its impact in effective orifice area.

BACKGROUND: The aim of this study is to see how the sutureless, stentless, Perceval S aortic valves behave when implanted in elderly patients with small aortic root and the comparison with a second group of patients with similar characteristics where a conventional stented bioprosthesis was implanted. This is a prospective randomized institutional study. METHODS: Our material is composed from 25 patients who underwent aortic valve replacement with sutureless self-anchoring Perceval S valve implantation (LivaNova), compared with 25 patients with conventional stented biological prosthesis implanted (soprano LivaNova group). The two groups of patients have similar demographic and medical characteristics with severe aortic stenosis. The study was conducted from January 2012 to June 2014. Preoperative, intraoperative and postoperative parameters were studied in order to investigate the utility of the Perceval S valves in this group of patients. RESULTS: The Perceval S valve implantation seems to be an interesting biological valve with good hemodynamic characteristics as compared with the typical biological prosthesis providing shorter ischemia time (40 ± 5.50 min vs 86 ± 15.86 min; p < 0.001), shorter extracorporeal circulation time (73.75 ± 8.12 min vs 120.36 ± 28.31 min p < 0.001), less operation time (149.38 ± 15.22 min vs 206.64 ± 42.85 min; p < 0.001) and better postoperative recovery. The postoperative gradients were 23.5 ± 19.20 mmHg vs 24.5 ± 19.90 mmHg respectively. The postoperative effective orifice area in these two groups were respectively 1.5 =/-0.19 cm(2) vs 1.1=/-0.5 cm(2) (p 0.002). Among the 25 patients of the Soprano stented valve, 3 (12 %) came back in 6 months with New York Heart Association (NYHA) 3. The PPM of these patients was the cause of readmission in the Hospital required diuresis and supplementary treatment. CONCLUSIONS: Aortic valve replacement with Perceval aortic valves in geriatric patients with comorbidities and small aortic annulus seems to be an alternative, safe and "fast" intervention with excellent short and mid-term results which provides a better effective orifice area.

Clinical Significance of Epsilon Waves in Arrhythmogenic Cardiomyopathy.

INTRODUCTION: Epsilon waves are hallmark features of arrhythmogenic cardiomyopathy (ACM) but information about their clinical significance is variable. We evaluated epsilon wave prevalence, characteristics, and their clinical significance in an ACM population. METHODS AND RESULTS: Eighty-six unselected patients fulfilling the 2010 Task Force criteria were enrolled. Seventy-six of them were carriers of desmosomal mutations. All subjects were serially evaluated with standard 12-lead ECG and 2-dimensional echocardiography. Epsilon waves were evaluated in all precordial and inferior leads. Novel parameters assessed included their duration and precordial/inferior lead extension. Twenty-five subjects (29%) had epsilon waves that were present in lead V3 and beyond in 9, and in the inferior leads in 7. Epsilon waves were associated with right ventricular outflow tract (RVOT) (P = 0.001) but not RV posterior wall (P = 0.21), RV apex (P = 0.30), or left ventricular (P = 0.94) wall motion abnormalities. Patients with epsilon waves had increased RVOT diameter (P < 0.0001). Extension of epsilon waves in lead V3 and beyond was associated with increased epsilon wave duration (P = 0.002) and RVOT diameter (P = 0.04). The duration of epsilon waves was positively correlated with RVOT diameter (r = 0.70, P = 0.0001). Epsilon waves were also associated with episodes of sustained ventricular tachycardia (P = 0.004) but not with heart failure (P = 0.41) or sudden cardiac death (P = 0.31). CONCLUSION: Detection of epsilon waves on 12-lead ECG reflects significant RVOT involvement, which was associated with episodes of sustained ventricular tachycardia but not sudden cardiac death.

Endocardial late potentials during sinus rhythm define the re-entry circuit of ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiomyopathy characterized by progressive fibro-fatty replacement of the right ventricular myocardium. We report a case where mapping of endocardial potentials during sinus rhythm identified the re-entry circuit of a recurrent ventricular tachycardia in a patient with ARVC. The tachycardia was subsequently ablated successfully.

Epsilon-like waves and ventricular conduction abnormalities in subjects with type 1 ECG pattern of Brugada syndrome.

BACKGROUND: Previous studies have demonstrated an overlap between the arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) and Brugada syndrome (BS). Conduction delay in the right ventricle has been demonstrated in both entities. OBJECTIVE: This study investigated specific ARVC/D electrocardiographic (ECG) markers in subjects with spontaneous or drug-induced type 1 ECG pattern of BS. METHODS: The study population consisted of 47 apparently healthy individuals (38 men, mean age 44.1 ± 13.3 years) with spontaneous (n = 17) or drug-induced (n = 30) type 1 ECG phenotype of BS. The clinical records of these individuals were retrospectively analyzed. RESULTS: Fifteen subjects (31.9%) were symptomatic, with a history of syncope. A family history of BS or sudden cardiac death was reported in 10 (21.3%) and 8 (17.0%) cases, respectively. Epsilon-like waves in leads V1-V3 were observed in 6 subjects (12.7%). Epsilon-like waves were seen in spontaneous type 1 ECGs in 2 cases and after sodium channel blocking test in 4 cases. In baseline ECGs, localized prolongation (>110 ms) of the QRS complex in leads V1-V3, QRS duration ratio in (V1+V2+V3)/(V4+V5+V6) ≥ 1.2, and prolonged S wave upstroke (>55 ms) in leads V1-V3 were seen in 48.8%, 29.8%, and 40.4% of subjects, respectively. Epsilon-like waves and delayed S wave upstroke were more commonly observed in subjects with family history of BS (P = .014 and P = .038, respectively). CONCLUSION: Specific ECG markers that reflect ventricular conduction delay in ARVC/D are commonly observed in subjects with spontaneous or drug-induced type 1 ECG pattern of BS as well. These depolarization abnormalities may be related to subtle underlying structural abnormalities.