108 CLINICAL RESEARCH INSTITUTE OF MEDICINE AND PHARMACY SCIENCE =========== NGO VAN THANH RESEARCH ON ARRHYTHMIA, HEART RATE VARIABILITY BY 24 – HOUR ELECTROCARDIOGRAM HOLTER IN PAT
Trang 1108 CLINICAL RESEARCH INSTITUTE
OF MEDICINE AND PHARMACY SCIENCE
===========
NGO VAN THANH
RESEARCH ON ARRHYTHMIA, HEART RATE VARIABILITY BY 24 – HOUR
ELECTROCARDIOGRAM HOLTER IN PATIENTS UNDERGOING CORONARY ARTERY BYPASS GRAFTING
Specialized: Internal Cardiology Code: 62.72.01.41
SUMMARY OF DOCTORAL DISSERTATION
HANOI – 2021
Trang 2CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES
Science supervisor:
1 Prof PhD: Nguyen Quang Tuan
2 PhD: Pham Truong Son
Reviewer 1: Associate Professor, PhD
Reviewer 2: Associate Professor, PhD
Reviewer 3: Associate Professor, PhD
The dissertation will be defended in front of the Council
Evaluation at:
………
The dissertation can be found at library of:
1 Vietnam National Library
2 108 Institute of clinical medical and pharmaceutical sciences
Trang 31 Ngo Van Thanh, Pham Truong Son, Nguyen Quang Tuan
(2021), “Heart rate variability in coronary artery bypass
grafting patients”, journal of 108 – clinical medicine and
pharmacy, volume 16 – No 2, pp 31 – 37
2 Ngo Van Thanh, Pham Truong Son, Nguyen Quang Tuan
(2021), “Arrhythmias in coronary artery bypass grafting
patients”, Vietnam medical journal, No 500, pp 144 – 49
3 Ngo Van Thanh, Pham Truong Son, Nguyen Quang Tuan (2021), “Relationship between heart rate variability and new – onset atrial fibrillation following coronary artery bypass
Trang 4INTRODUCTION THESIS
1 BACKGROUND
Coronary artery bypass graft (CABG) surgery with extracorporeal circulation is one of the basic treatments for coronary artery disease, but cardiovascular events and arrhythmias can still occur after surgery Cardiac arrhythmias commonly occurring after surgery include atrial fibrillation (AF) (5-40%), ventricular tachycardia (26.6%), and ventricular fibrillation (2.7%) Arrhythmia
is the cause of 50% of deaths after surgery Among arrhythmias, ventricular arrhythmias and AF after CABG are of the most research interest However, up to now, the authors have not come up with a unified opinion on the influencing factors as well as the prognostic value in patients with ventricular arrhythmias and AF after surgery Some authors believe that postoperative ventricular arrhythmias do not have a bad prognosis, AF occurring after the surgery is of concern Postoperative AF reduces the quality of life, reduces physical activity, and contributes to increased mortality, stroke, and other thromboembolic events About 10% of patients with AF after CABG leading to brain stroke
Of the arrhythmias mentioned above, only 5-10% can be detected by routine 12-lead ECG, increasing to 40-60% with a 24-hour ECG Holter It has been found that the autonomic nervous system acts as a risk factor for the development of arrhythmias ECG Holter has a role not only in assessing arrhythmias but also indirectly
in assessing autonomic nerve activity through heart rate variability (HRV) This is one of the predictors of arrhythmia and cardiovascular events
Studies on CABG patients have shown a decrease in HRV perioperative However, results on the association between reduced HRV and arrhythmias and cardiovascular events are still inconsistent Some authors found a decrease in HRV to be associated with arrhythmias and cardiovascular events, and that a reduction in preoperative HRV had predictive value in the occurrence of arrhythmias Meanwhile, some other authors have not found this association Thus, it is necessary to further elucidate the characteristics of arrhythmia and HRV in CABG patients In
Trang 5Vietnam, there have been several studies on arrhythmia, HRV in CAD patients undergoing medical treatment and CPI However, for CABG patients, these characteristics have not been studied Therefore, we conducted this study with the following objectives:
1 Investigate the arrhythmia, heart rate variability by 24-hour Holter electrocardiogram in patients before and after coronary artery bypass graft surgery
2 Evaluation of the relationship between arrhythmia, heart rate variability with some clinical and subclinical characteristics, and major cardiovascular events within 6 months in patients undergoing coronary artery bypass graft surgery
2 NEW CONTRIBUTIONS OF THE THESIS
The thesis has shown the relationship between HRV and arrhythmia in perioperative CABG patients The thesis has also shown the relationship between HRV, arrhythmia, and major cardiovascular events after surgery These are contributions to the specialty of cardiology These results also help intensivists and cardiologists to have strategies to prevent arrhythmias or use anticoagulation to prevent embolism in cases at risk of developing
AF
3 THE LAYOUT OF THE DISSERTATION
The dissertation has 128 pages including sections: Introduction (2 pages), chapter I: Overview (31 pages), chapter II: Objects and research methods (25 pages), chapter III: Results (33 pages), Chapter IV: Discussion (33 pages), Conclusion (2 pages), Recommendations (1 page) The dissertation has 46 tables, 11 charts, 11 pictures, and used 136 references (19 Vietnamese documents, 117 English documents)
Chapter 1 OVERVIEW DOCUMENT 1.1 Chronic coronary artery disease, diagnosis, and treatment 1.1.1 The concept of chronic coronary artery disease
Chronic CAD is a disease related to the relative stability of coronary atherosclerotic plaque, in the absence of abrupt rupture or
after the acute phase or after intervention/surgery Chronic coronary
artery syndrome is a new term introduced by the ESC (2019) to
Trang 6replace the previous names of stable angina, chronic CAD, and
chronic ischemic cardiomyopathy calculation or coronary failure 1.1.2 Diagnosis of chronic CAD
1.1.2.1 Clinical symptoms
1.1.2.2 Diagnostic tests and investigations
* Basic tests and probes:
* Non-invasive diagnostic exploration:
* Invasive diagnostic exploration:
1.1.3 Methods of treatment of chronic CAD
The principle of treatment of chronic CAD is to prevent MI, improve survival and improve symptoms for patients
1.1.3.1 Medical treatment
1.1.3.2 Treatment of chronic CAD by CPI and by CABG
* Angioplasty and stenting:
1.1.4.2 Indications
1.1.4.3 Techniques
- CABG with extracorporeal circulation
- CABG without extracorporeal circulation
- Minimally invasive CABG
- CABG combined with PCI
- CABG and stem cell therapy:
1.1.4.4 Cardiovascular events postoperative
* Non-cardiac complications affecting the heart postoperative:
* Major cardiovascular events postoperative:
Major cardiovascular events postoperative include death, stroke, MI, and heart failure
1.2 ECG Holter
1.2.1 History and principles
ECG Holter, also known as an ambulatory ECG, is used to detect and record electrical abnormalities that occur during normal daily activities
Trang 71.2.2 Indications, contraindications, and technique
1.2.2.1 Indications and contraindications
1.2.2.2 ECG Holter recording technique
1.2.3 Evaluation of arrhythmia on 24-hour ECG Holter
Heart rate: Total number of beats in 24 hours divided by 1440 minutes, slowest heart rate recorded in 24 hours, fastest heart rate recorded in 24 hours
The bradycardia, the tachycardia, and the duration of the attack + Sinus stop:
+ Sinus tachycardia (frequency > 100 beats/min)
+ Sinus bradycardia (frequency < 60 beats/min)
Arrhythmia (according to the criteria of Remi pillière):
+ Atrial septal defect: The normal limit is < 10 atrial ventricular systole/24 hours for people 20-40 years old; < 100 atrial NVT/24 hours for 40-60 years old; < 1000 atrial NVT/24 hours for people >
60 years old;
+ Types of the ventricular septal defect (singular, double beam, triple cluster, double ventricular, triple rhythm, and R/T presentation) + Supraventricular tachycardia: when there are > 3 consecutive ventricular beats
Evaluation of ventricular arrhythmias by Holter ECG based on the classification criteria and classification of ventricular arrhythmias according to Lown
1.2.4 Evaluation of HRV on 24-hour ECG Holter reflecting autonomic nerve
1.2.4.1 Effects of the autonomic nervous system on the heart
The role of the sympathetic nervous system on the heart:
The role of the parasympathetic nervous system on the heart:
1.2.4.2 Autonomic nerve assessment methods
1.2.4.3 The concept and assessment of HRV by 24-hour ECG Holter HRV is the variation in the cardiac cycle, calculated as the change in the interval between successive heartbeats on the ECG
There are many ways to assess HRV on ECG, but only HRV by frequency spectrum and time domain is widely applicable in clinical practice
* Evaluation of HRV by time domain:
Trang 8Terms used to describe HRV indices according to the ESC and the NASE-Pacemaker (1996) include:
Mean NN (average NN interval): is the average of the distances of successive R waves in the entire ECG recording
SDNN (standard deviation of span to span in 24 hours): reflects the effects of both sympathetic and parasympathetic nervous systems SDANN (standard deviation of spans to beats every 5 min over 24 hours):
SDNN index or ASDNN: is the average of the standard deviation of SDANN (5-minute intervals over the whole 24 hours)
rMSSD: is the square root of the average of the squares of SDNN pNN50: is the percentage of consecutive beats to beats that differ by >
50 ms with the intervals to normal heart rate
* Evaluation of HRV by frequency spectrum:
Terms according to the ESC and the NAS of Pacemaker (1996) include:
Electrophysiology-Total power (TP): is the sum of all values, also known as the magnitude of the HRV according to the frequency spectrum (ms2) Ultra Low Frequency (ULF): is the beat-to-beat oscillation in the frequency range <0.0033Hz (ms2)
Very Low Frequency (VLF): is a beat-to-beat oscillation in the frequency range from 0.003–0.04Hz (ms2)
Low Frequency (LF): is the beat-to-beat oscillation in the frequency range from 0.04-0.15 Hz (ms2)
High Frequency (HF): is the beat-to-beat oscillation in the frequency range from 0.15-0.40Hz (ms2)
LF/HF: This ratio reflects the sympathetic-parasympathetic balance This index reflects changes in HRV due to sympathetic or parasympathetic nerves
1.3 Arrhythmia, HRV in CABG patients
1.3.1 Arrhythmias in CABG patients
1.3.1.1 General mechanism causing arrhythmia
1.3.1.2 Factors affecting arrhythmia in CABG patients
* Background medical condition:
* Perioperative factors:
1.3.1.3 Common arrhythmias post CABG
Trang 9* Supraventricular arrhythmias:
- Bradycardia: - Conduction disturbances:
- Supraventricular tachyarrhythmias: - Atrial flutter (Flutter):
- AF: occurs post CABG leading to 10-40%
* Ventricular arrhythmias:
- Ventricular extrasystoles - Short ventricular tachycardia
- Sustained ventricular tachycardia and ventricular fibrillation
1.3.2 Heart rate variability in CABG patients
1.3.2.1 Factors affecting HRV in CABG patients
* Non-coronary artery disease factors:
* Factors associated due to CAD and CABG:
1.4 Domestic and international research
MI patients
Study HRV by 24-hour ECG Holter in chronic CAD patients, Nguyen Nam Giang (2016) commented that HRV was lowest in the coronary artery occlusion group, followed by narrow and moderate stenosis The limitation of the study is that the author only evaluated a time point, not assessing the long-term evolution of HRV due to treatment
1.4.2 International research
Elisabeth (2017) found that 100% ventricular extrasystoles, 82.9% double ventricular extrasystoles and 48.6% ventricular tachycardia occurred mainly on the first day and then gradually decreased The limitation of this study is that the author only followed up to the first 5 days postop, not long-term evaluation because arrhythmias after surgery are affected by many factors
Trang 10Ameli (2013) studied 856 CABG patients showing that ventricular tachycardia has a rate of 26.6%, ventricular fibrillation is 2.7%, of which the rate of ventricular fibrillation is highest in the first
48 hours postop (accounting for 61%) Patients with ventricular fibrillation are at risk of recurrence The author noted the risk of ventricular arrhythmias in the first 48 hours postop
Takeshi Kinoshita (2011) showed that AF occurred in 98 patients, accounting for 25% postop and preoperative HRV was related to postoperative AF
Yavuz (2006) found that at 2 time points 2-5 days preop and 10 days postop, HRV postop was lower than preop
Godoy (2009) found that decreased preoperative HRV increased postoperative mortality
Milicevic (2004) studied 175 patients (124 MI patients and 51 CABG patients) showed that reduction in HRV postop CABG had less predictive value for mortality than MI patients group
Thus, studies on arrhythmias and HRV are incompleted There has not been a study on the prognostic value perioperative CABG between arrhythmias, HRV with some clinical and subclinical
characteristics and cardiovascular events during long-term follow-up
Chapter 2 RESEARCH SUBJECTS AND METHODS
2.1 Research subjects
2.1.1 Criteria for selecting research subjects
The study patients met all three of the following criteria:
Chronic CHD patients, with an indication for CABG as
recommended by the VHA (2008), the guidelines of the AHA (2011), and the EHA (2013)
Patients has sinus rhythm based on 24h ECG Holter preop CABG CABG used extracorporeal circulation
Trang 11- ECG Holter recording time is less than 18 hours, there are many noisy signals
- Patients with hemodynamic instability (using vasopressors, mechanical ventilation) at the recording ECG Holter preop
- Emergency CABG, CABG do not use extracorporeal circulation
- CABG combined with valve replacement, aortic segment replacement or congenital heart disease surgery
- Patients had complications requiring surgery: bleeding, infection
- Death from complications during and postop related to surgery (such as blood loss, bleeding)
- The patients did not agree to participate in the study
- The patients do not followed up adequately after surgery
2.2 Research Methods
2.2.1 Research design
- Methods: prospective, descriptive, with longitudinal follow-up
- Sample size and convenient sampling method: all subjects in our study were selected in chronological order (from June, 2016 to August, 2018), regardless of age, gender as well as comorbid conditions at the time of admission of the patient
2.2.2 Steps to conduct research
Step 1: Select eligible patients for the study
Step 2: Collect research information before surgery
Step 3: Carry out CABG, collect research information on the postoperative period of hospital stay
Step 4: Monitor and collect information on the 3rd and 6th month follow-up period to evaluate the following parameters:
- 3rd month: echocardiography and 24h-ECG Holter for the 3rd time Summary of major cardiovascular events
- 6rd month: echocardiography and 24h-ECG Holter for the 4rd time Summary of major cardiovascular events
Trang 122.2.4 Record 24h-ECG Holter and analyze the results
2.2.4.1 Procedure ECG Holter recording technique
Location of conducting ECG Holter technique and processing results: Holter Room - Department of Diagnostic Imaging, Hanoi Heart Hospital
Technical process:
- Prepare patient and machine recorder
- Prepare the patient:
- Place electrodes: arrange 7 electrodes glued on the patient's chest skin to create 3 leads corresponding to 3 channels (Figure 2.2)
- Turn on the machine, set the recording mode, recording time 24 hours
- After 24 hours of disassembling the device, transfer the data to the computer
2.2.4.2 Arrhythmia analysis
Based on the software to process the data, the analysis steps include:
- Normalize data on fastest beat, slowest beat, remove noise signals
- Standardization of data on arrhythmias
- Select typical arrhythmia templates to print results
2.2.4.3 Analysis of heart rate variability
- Check heart rate, arrhythmias and HRV
- Do not analyze HRV after CABG when there is one of the following signs: AF, sick sinus node, second-degree or third-degree A-V block
2.2.4.4 Summarize and read the results
- Heart rate: basal heart rate, average, min, max
- Arrhythmias: atrial arrhythmias, conduction disturbances and ventricular arrhythmias
- HRV: by time domain and by frequency spectrum
2.2.5 Medical treatment before and after surgery
For ethical reasons in biomedical research, we did not stop drugs
affecting the study results HRV for research
Trang 13Clinical features
Features of surgery and treatment after surgery
2.3.2 Paraclinical features
- Blood tests - Echocardiography evaluation
- EuroSCORE II scale or EuroSCORE logistic regression
- Evaluation of coronary artery injury by percutaneous coronary angiography
- 12-lead electrocardiogram:
2.3.3 Evaluation of arrhythmia and HRV by 24h ECG Holter
Arrhythmia criteria:
- Sinus bradycardia: < 60 beats/min
- Sinus tachycardia: > 100 beats/min
- Sinus arrest: R-R interval > 2.5 seconds
- Paroxysmal supraventricular tachycardia: when there are > 3 consecutive beats of the atrial complex and > 140 beats/min
- Evaluation of AF: AF at lasts ≥ 30 seconds, recorded
- Ventricular extrasystoles: premature beats > 40% Includes monomorphic ventricular ectopic, double, triple, and R/T ventricular ectopic
- Ventricular tachycardia: > 3 consecutive ventricular extrasystoles, rate > 100 beats/min
+ Transient ventricular tachycardia: the episode lasts < 30 seconds + Persistent ventricular tachycardia: tachycardia > 30 seconds
- Evaluation of ventricular arrhythmias according to Lown:
+ Grade 0: No ventricular extrasystoles;
+ Grade I: uniform, <30 ventricular premature beats/hour;
+ Grade II: monomorphic, ≥ 30 ventricular beats/hour;
+ Grade III: multiform ventricular extrasystoles;
+ Grade IVa: 2 consecutive ventricular extrasystoles (couplets); + Grade IVb: 3 consecutive ventricular extrasystoles (salvos);
+ Grade V: premature ventricular extrasystoles, R on T
Evaluation of HRV:
Time domain measurements of HRV:
- Mean NN (or average NN): - SDNN: - SDANN: - SDNN index or ASDNN: - rMSSD: - pNN50:
Trang 14Criteria to evaluate the reduction of HRV: at least one of the
following indicators has decreased to the limit level (table 2.3)
Table 2.3 Diagnostic value of low heart rate variability by time domain and association with autonomic nervous system
autonomic
nervous system
frequency spectrum Time domain Low HRV
parasympathetic HF rMSSD rMSSD < 15 ms
pNN50 pNN50 < 0,75 % Sympathetic,
parasympathetic LF
SDNN index (or ASDNN) ASDNN < 30 ms Sympathetic,
parasympathetic VLF
SDNN index (or ASDNN) ASDNN < 30 ms Sympathetic,
parasympathetic ULF
SDNN SDNN < 50 ms SDANN SDANN < 40 ms The indicators of heart rate variation according to the frequency spectrum (ms2)
Chapter 3 RESEARCH RESULTS 3.1 Some clinical, paraclinical, surgical, treatment and postoperative characteristics of the study patients
In our study, there were 119 patients with age from 38 to 81 years old, mean age 64.92 ± 7.34 years old Male gender accounted for the majority (83.2%), higher than female with the rate of 16.8%
Table 3.9 The main cardiovascular event rates after CABG
Cardiovascular event
Total (n=119)