Tóm tắt Luận án Study on electrophysiological properties and the efficacy of catheter – based radio frequency ablation of paroxysmal atrial fibrillation

MINISTRY OF EDUCATION AND TRANING MINISTRY OF NATIONAL DEFENCE MILITARY MEDICAL UNIVERSITY PHAM TRAN LINH STUDY ON ELECTROPHYSIOLOGICAL PROPERTIES AND THE EFFICACY OF CATHETER – BASED RADIO FREQUENCY ABLATION OF PAROXYSMAL ATRIAL FIBRILLATION Speciality: Medical Cardiology Code: 62720141 ABSTRACT OF MEDICAL PHD THESIS HA NOI – 2016 Training institution: MILITARY MEDICAL UNIVERSITY Instructors: 1. NGUYEN LAN VIET, MD.PHD.Prof. 2. PHAM QUOC KHANH, MD.PHD. The 1st opponent: Doan Van De, MD.PHD.Prof. The 2nd opponent: Do Doan Loi, MD.PHD.Prof. The 3rd opponent: Tran Van Riep, MD.PHD.Prof. This thesis will be presented at the commission for theses of Military Medical University At hours of day month year This thesis may be found at: 1. The National Library 2. The Library of Military Medical University 3. The Library of Bach mai General Hospital LIST OF PUBLISHED SCIENTIFIC WORKS RELATED TO THE THESIS 1. Pham Tran Linh, Pham Quoc Khanh, Nguyen Lan Viet (2015), "Initial evaluation of the effectiveness of catheter – based radio frequency ablation of paroxysmal atrial fibrillation", journal of Vietnamese Medical, 429 (2), pp. 144 - 150. 2. Pham Tran Linh, Pham Quoc Khanh, Nguyen Lan Viet (2015), "Clinical manifestations and electrophysiologic features in patients with paroxysmal atrial fibrillation", journal of Vietnamese Medical, 430 (1), pp. 159 - 165. INTRODUCTION Atrial fibrillation (AF) is one of the most common types of arrhythmia. AF is associated with a wide range of complications in clinical practice and may contribute to 5% of stroke cases a year. Mortality may increase to 34% in patients with heart failure if AF is concomitant. It is known that AF increases in the prevalence with advancing age. The incidence of AF is approximately 0.1% in the patients under 40 years of age while it approaches 1.5 – 2% in the group over 60 years of age. It was the first time in 1994 when Haissaguerre utilized the radio frequency (RF) energy as a therapy for AF patients. Nevertheless, this method had limitations such as low successful rate of 33 – 60%, high rate of complications, long procedure time (5 – 6 hours). In 1996, Pappone used a three dimensional mapping system named CARTO to facilitate the therapy of AF with RF energy. CARTO system has brought higher efficacy in the treatment of AF as it guarantees high successful rate and low complication rate. The system has been upgrading so far to vast the utility in RF ablation of AF as the most advanced curing method for the disease. Back to 1998 when RF energy was first settled in Vietnam Heart Institute – Bach Mai Hospital, then was widespreaded to other heart centers up and down the country, launching the initiation for the interventional rhythmology in Vietnam. However, paroxysmal AF has not been treated with RF energy as a routine procedure in Vietnam. Some questions have been raised to require the answers. What are the electrophysiological properties of the paroxysmal AF in Vietnamese patients ? What are the posibilities to utilize the therapy and its limitations ? What are the optimal indications for Vietnamese patients ? What are the early outcomes and the follow-up results ? In contributing to bring this method into routine practice in Vietnam, we conduct a research named “Electrophysiological properties and the efficacy of catheter – based radio frequency ablation of paroxysmal atrial fibrillation”. Objectives of our research are: Cardiac electrophysiological properties of paroxysmal atrial fibrillation patients. Evaluation of short-term outcomes of radio frequency ablation of paroxysmal atrial fibrillation. * Contributions of the research: Paroxysmal atrial fibrillation often originates from the four pulmonary veins with 83.3% were from left pulmonary veins and rarely comes from right atrium. In episodes of atrial fibrillation, the average A-A intervals were 196.8 ms and V-V intervals were 574.4 ms. Radio frequency ablation of paroxysmal atrial fibrillation has a high successful rate. Sinus maintenance rate was reached at 88.1% just after procedures and 74.3% after 12 months of follow-up. Recurrence rate was 11.4% and complication rate was 4.7% with no death. * Structure of the thesis: The thesis consists of 136 pages (not including appendix and list of references), 50 tables, 10 graphs and 33 figures. There are 132 reference documents, including 12 in Vietnamese and 120 in English. There are 3 pages for the part of Introduction, 36 pages for Overview, 21 pages for Object and Methodology, 33 pages for Research Result, 39 pages for Discussion, 3 pages for Conclusion, 1 page for Suggestion. CHAPTER 1 OVERVIEW 1.1. ELECTROPHYSIOLOGICAL PROPERTIES OF THE LEFT ATRIUM ANATOMY AND CARDIAC CONDUCTION SYSTEM 1.1.1. Left atrium anatomy: left atrium is bordered by the pulmonary veno-atrial junctions, atrio-ventricular junction at the mitral orifice, the left appendage and the septal part. - Left atrium’s walls and atrial septum: left atrium’s walls include anterior wall, superior wall, free wall (lateral wall), posterior wall and septal wall. - Atrial muscle: the left atrium consists of three layers: epicardium, atrial muscle and endocardium. The atrial musculature is constructed by circumferential and longitudinal muscular bundles. Those bundles contribute to the formation of pectinate muscles of the atrium. - Pulmonary veins and ostia: all four pulmonary veins enter the left atrium at the posterior wall. In most of cases, those pulmonary veins are separated. 1.1.2. Conduction system: Sinus node, internodal pathways, atrioventricular node, His bundle and branches, Purkinje fibers. 1.2. ELECTROPHYSIOLOGICAL PROPERTIES AND CONDUCTION SYSTEM Including activation potential, excitability, automaticity, conductivity and refractoriness. 1.3. PATHO-PHYSIOLOGY IN ATRIAL FIBRILLATION 1.3.1. Electrophysiological mechanisms: 3 mechanisms for AF has been explained: Single micro re-entrant stable circuits. Frequently macro re-entrant unstable circuits. Single automatic focus firing short interval impulses. 1.3.2. Hemodynamic Consequences: hemodynamic consequences of AF result from multi factors such as loss of atrial contraction, irregular ventricular response, rapid ventricular rate, coronary hypoperfusion. 1.3.3. Mechanisms of thrombosis in AF: Patho-physiology of thrombosis in patients with AF is complicated. Virchow’s triad contributes 3 factors in leading to thrombosis: blood stasis, alteration of vessels’ intimal function and blood hypercoagulability. 1.4. DIAGNOSIS OF ATRIAL FIBRILLATION 1.4.1. Classification of AF based on clinical settings: - Paroxysmal AF: AF that terminates spontaneously or with intervention within 7 days of onset, commonly within 48 hours. - Persistent AF: AF that sustains over 7 days from onset and be terminated by pharmacological or direct-current cardioversion. - Permanent AF: is persistent AF that can not terminate by pharmacological or direct-current cardioversion. 1.4.2. Etiology: valvular heart diseases (mitral stenosis or mitral regurgitation), coronary artery diseases, left ventricular dysfunction, hypertension, left ventricular hypertrophy, congenital heart diseases including atrial septal defect, transposition of great vessels ; hyperthyroidism, idiopathic AF 1.4.3. Diagnosis: diagnosis of AF bases on routine electrocardiograms. Some investigations can be doned to diagnose the etiology of AF including thyroid hormones, echocardiography, chest X-ray, stress test, 24 hour ECG monitoring, event recorder, electrophysiological study. 1.4.4. Principles of treatment: rhythm control and thrombosis prevention. Based on the classification of AF, medications, interventional procedures or other methods can be chosen. 1.5. CATHETER – BASED RADIO FREQUENCY ABLATION. 1.5.1. Published international researches: It was the first time in 1994 when Haissaguerre utilized the radio frequency (RF) energy as a therapy for AF patients. Nevertheless, this method had limitations such as low successful rate of 33 – 60%, high rate of complications, long procedure time (5 – 6 hours). In 1996, Pappone used a three dimensional mapping system named CARTO to facilitate the therapy of AF with RF energy. 1.5.2. Research in the issue in Vietnam: It was not until 2009 when the first AF case was ablated using catheter-based radio frequency. 1.5.3. Patient selection: Following the 2010 ACC/AHA/ESC Guidelines for Management of patients with Atrial Fibrillation. 1.5.4. Result of the intervention: Analysis from the data of 4000 thousand cases in Cleveland Clinic shows that the successful rate is 80%. 1.5.5. Complications: Some complications have been reported including vascular access complications, cardiac perforation, cardiac tamponade, valvular injury, stroke or TIA, systemic thrombosis, atrial-esophagus fistula, pulmonary vein stenosis ... CHAPTER 2 OBJECTS AND METHODOLOGY 2.1. OBJECTS Our research includes 42 patients who were diagnosed paroxysmal atrial fibrillation and hospitalized from October of 2009 to March of 2014. 2.1.1. Selection Criteria Following the guidelines of American College of Cardiology, American Heart Association, European Society of Cardiology (ACC/AHA/ESC) 2010. Patients were diagnosed symptomatic paroxysmal atrial fibrillation, with EHRA symptom score ≥ 2, refractory to pharmacological agents including rate control and rhythm control (Indication Class IIa, Level of evidence A). 2.1.2. Exclusion Criteria Severe heart failure (NYHA IV), valvular AF cases that have the indication for open heart surgery, acute infections, coagulation disorders, heart chamber thrombus, persistent AF and permanent AF. 2.2. METHODOLOGY 2.2.1. Research design Cohort study. 2.2.2. Object selection Objects were selected based on the timeline. 2.2.3. Clinical examination and investigations All the patients were examined, recorded 12 – lead ECG, monitored 24 hour ECG recordings. Other investigations were done before procedures such as blood tests, chest X-ray, transthoracic echocardiography, transesophagus echocardiography, multi-sliced CT scanner of left atrium and pulmonary veins. 2.2.4. Electrophysiological study + Place of procedures: Laboratory of Catheterization, Vietnam Heart Institute, Bach Mai Hospital. + Equipments:angiography system, stimulator, electrophysiological recording system, ablation generator, three dimensional mapping system (CARTO system) and varieties of diagnostic catheters and ablation catheters. +Pre-procedure preparation: patients were explained about the purpose, techniques, possible outcomes and complications of the procedures. + Procedure protocol - Placement of catheters . Diagnostic catheters were placed at the coronary sinus, right atrium, right ventricle, His bundle. . Mapping catheters and ablation catheters were inserted through right femoral vein and transseptally to the left atrium. - Electrophysiological protocols . Electrophysiological properties in sinus rhythm: we measured PA, AH, HH, HV intevals, QRS duration, QT duration, basic sinus cycle length. . Programmed stimulation protocols: rapid atrial pacing, extra stimulus atrial pacing, rapid ventricular pacing, extra stimulus ventricular pacing. - Electrophysiological characteristics of Atrial Fibrillation . Localization of prematured atrial complexes triggering atrial fibrillation: action potentials were recorded in different regions within the atrium. Prematured atrial complexes that trigger episodes of AF were normally recorded earlier than in other regions. . Measurements of intervals during AF: A-A intervals, V-V intervals. 2.2.5. Radio frequency catheter ablation protocol of AF + Septal puncture:diagnostic catheters and ablation catheter were inserted from the right side to the left atrium. + A multi electrode catheter (Lasso catheter) were put to record action potentials inside the ostia of four pulmonary veins. + A three dimensional image of the left atrium was created. + Pulmonary veins were isolated and other triggering foci of AF in the left and right atrium were also ablated. + Criteria of success: - Cardioversion of sinus rhythm. - No electrical connections were found between left atrial chamber and the pulmonary veins. - No episodes of AF were inducible during programmed electrical stimulation. 2.2.6. Follow-up after radio frequency catheter ablation + All the patients were monitored at the Cardiac Intensive Care Unit after the procedures. Parameters such as hemodynamics, echocardiography, electrocardiograms were obtained. + Patients with successful ablations were received antiarrhythmic 3 months after procedures. + Follow-up was carried out with 24 – hour ECG monitoring after 1 month, 3 months, 6 months, 12 months from the procedures. + Anti-coagulant therapy was also given in 3 months with VKA targeting INR from 2 to 3, or NOAC. Study’s protocol 2.3. STATISTICAL ANALYSIS Statistical analysis was facilitated by software package SPSS version 17.2 (2007). CHAPTER 3 RESULT 3.1. GENERAL CHARACTERISTICS OF PATIENTS From October of 2009 to March of 2014, 42 patients with AF that unresponsive to pharmacological agents were indicated to undergo radio frequency catheter ablation. 3.1.1. Age and gender There were 36 male patients (85.7%) and 6 female patients (14.3%). Table 3.1. Age and gender Age group Male (n=36) Female (n=6) Total (n=42) Number % Number % Number % ≤ 50 12 33.3 2 28.5 14 32.6 51 - 60 9 25.0 2 28.5 11 25.6 ≥ 61 15 41.7 2 42.9 17 41.9 3.1.2. Clinical parameters Table 3.2. Clinical parameters (n=42) Parameters Mean Weight (kg) 64.2 ± 8.8 46 – 80 Height (m) 1.63 ± 0.06 1.50 – 1.74 BMI (kg/m2) 24.0 ± 2.2 18.4 – 28.7 Heart rate (bpm) 76.0 ± 13.5 54 – 120 Systolic pressure (mmHg) 124.6 ± 15.3 100 – 180 Diastolic pressure (mmHg) 78.0 ± 10.2 60 – 100 Table 3.3. Characteristics of AF (n=42) Index Number (n=42) % Years from onset 5.0 ± 3.5 Episodes / month 6.9 ± 9.4 EHRA symptom score 3.19 ± 0.45 Termination: Spontaneously 39 90.7 Pharmacological cardioversion 29 67.4 Direct current Cardioversion 4 9.3 Medications: Amiodarone 38 88.4 Group IA 8 18.6 Group IC 15 34.9 Group II 11 25.6 3.1.5. Twenty four - hour ECG monitoring characteristics Table 3.4. Characteristics of 24-hour ECG recordings (n=42) Index Mean Range Average heart rate (bpm) 82.6 ± 13.5 64 – 115 Total time of bradycardia (< 60 bpm) 185.2 ± 217.5 0 – 827 Number of episodes of AF 9.3 ± 20.9 1 – 107 Average duration of AF episodes 461.4 ± 590.6 1 – 1.444 Number of PACs 1195.5 ± 1861.6 0 – 8.019 Couplet PACs 203.1 ± 684.4 0 – 3.850 Triplet PACs 32.7 ± 64.7 0 – 288 Atrial Tachycardia 10.4 ± 399.3 0 – 258 3.2. ELECTROPHYSIOLOGICAL CHARACTERISTICS IN PATENTS WITH PAROXYSMAL AF 3.2.1. At baseline with sinus rhythm 3.2.1.1. Basic intervals Table 3.5. Basic intervals Index ≤ 60 y (n=25) > 60 y (n=17) P Overall Basic cycle length (ms) 760.2±188.8 886.7±113.5 0.021 810.8 ± 172.9 PA intervals (ms) 21.0 ± 5.1 23.9 ± 5.2 0.124 26.7 ± 8.6 AH intervals (ms) 91.7 ± 18.3 88.1 ± 12.3 0.092 90.5 ± 15.9 His duration (ms) 19.0 ± 6.9 18.1 ± 2.9 0.488 18.7 ± 5.6 HV intervals (ms) 47.4 ± 5.7 48.1 ± 3.9 0.618 47.7 ± 5.0 QRS duration (ms) 91.3 ± 11.9 91.2 ± 13.4 0.975 91.3 ± 12.4 QT intervals (ms) 389.3 ± 42.2 391.4±29.3 0.834 390.2 ± 30.7 42 patients were divided into 2 groups based on age. A group consisted patients ≤ 60 years of age and the other one consisting patients > 60 years of age. The basic cycle length of patients ≤ 60 years of age were significantly shorter than those of > 60 years of age. There was no significant difference between the measurements of other intervals. 3.2.1.2. Electrophysiological study of sinus node function Table 3.6. Sinus node recovery time (SNRT)and corrected sinus node recovery time (cSNRT) based on age and gender Index SNRT (ms) p cSNRT (ms) p Gender Male (n=36) 1181.8 ± 201.0 0.523 310.8 ± 143.2 0.169 Female (n=6) 1120.7 ± 170.6 403.7 ± 89.2 Age ≤ 60 (n=25) 1140.6 ± 190.5 0.207 319.8 ± 114.1 0.881 > 60 (n=17) 1222.0 ± 200.9 326.8 ± 174.9 Overall (n=42) 1173.9 ± 196.4 322.7 ± 140.1 There was no significant difference in the SNRT between the male and female group (p > 0.05). No significant difference was found between the cSNRT of the patients > 60 years of age and the patients ≤ 60 years of age. 3.2.1.3. Effective refractory periods (ERP) of the atrium and ventricle Table 3.7. ERP of the atrium and ventricle Index Atrial ERP (ms) Ventricular ERP (ms) Atrio-ventricular dissociation point (ms) ≤ 60 y (n=25)1 198.7 ± 19.4 218.7 ± 58.7 395.3 ± 21.0 > 60 y (n=17)2 215.6 ± 15.9 222.5 ± 15.3 426.3 ± 73.5 Overall (n=42) 205.6 ± 19.7 220.3 ± 17.2 407.9 ± 66.1 P1,2 0.007 0.505 0.001 The atrial ERP and ventricular ERP were within the normal range. There was no significant difference between two groups of age. The atrial ERP of the patients ≤ 60 years of age was significantly shorter than the group of > 60 years of age with p = 0.007. 3.2.2. Electrophysiological characteristics in AF Atrial programmed electrical stimulations were performed to induce AF and then action potentials were recorded at different locations in the left atrium. 3.2.2.1. Locations of PACs triggering episodes of AF Table 3.8. Locations of PACs triggering AF (n=42) Location Number % Right atrium Superior vena cava 2 4.8 Inferior vena cava 0 0 Right atrial isthmus 2 4.8 Left atrium Left superior PV 35 83.3 Left inferior PV 30 71.4 Right superior PV 33 78.6 Right inferior PV 31 73.8 Left appendage 7 16.7 Left atrial isthmus 2 4.8 Over 70% of PACs originated from pulmonary veins, whilst up to 83.3% of those were from left superior PA. 3.2.2.2. Interval recordings in AF Table 3.9. Interval recordings based on group of age Index ≤ 60 y (n=25) > 60 y (n=17) P Overall (n=42) Average AA intervals (ms) 201.1 ± 35.7 194.7 ± 41.7 0.629 196.8 ± 39.5 Shortest AA intervals (ms) 135.6 ± 39.4 123.1 ± 29.9 0.261 127.3 ± 33.4 Longest AA intervals (ms) 263.1 ± 51.5 249.8 ± 38.1 0.346 254.2 ± 42.9 Average VV intervals (ms) 543.7±104.4 589.8 ±107.8 0.194 574.4 ±107.6 Shortest VV intervals (ms) 350.0 ± 88.6 415.3 ±102.2 0.049 393.5 ±101.7 Longest VV intervals (ms) 813.8±191.5 827.6 ±205.0 0.834 823.0 ±198.4 The role of AV conduction is important in reducing the impulses travelling from atria to ventricles to maintain tolerant ventricular response. 3.3. RESULTS OF PAROXYSMAL ATRIAL FIBRILLATION ABLATION 3.3.1. Results of procedures 3.3.1.1. Procedure time Table 3.10. Procedure time Index Overall (n=42) PV isolation (n=28) Other ablation sites (n=14) P Procedure time (min) 288.8 ± 60.4 293.6 ± 58.9 265.0 ± 68.8 0.173 Fluoroscopic time (min) 64.6 ± 20.4 69.4 ± 16.7 54.9 ± 24.2 0.028 Time for creating image and mapping (minute) 40.9 ± 12.2 41.9 ± 14.0 38.3 ± 6.2 0.371 Ablation points 115.9 ± 35.9 113.6 ± 34.1 125.6 ± 38.6 0.372 Total ablation time (seconds) 3476 ± 852 3644 ± 850 3224 ± 817 0.129 The average procedure time was 288.8 ± 60.4 minutes. Time for creating image of left atrium and PVs and mapping tim was 40.9 ± 12.2 min. The total RF ablation time was 3476 ± 852 seconds. The flouroscopy time was 64.5 ± 20.4 min. 3.3.1.2. Pulmonary vein isolation Table 3.11. Parameters for PV isolation (n=42) Index Left PVs Right PVs Anterior wall Posterior wall Anterior wall Posterior wall Number of ablation points for a single line 37.5 ± 12.2 35.8 ± 12.7 33.2 ± 9.7 34.5 ± 14.0 Power (W) 32.4 ± 2.5 22.6 ± 3.2 29.9 ± 1.4 28.8 ± 2.2 Tempe