MILITARY MEDICAL ACADEMYDOAN THINH TRUONG RESEARCH ON THE RELATIONSHIP BETWEEN PLASMA NT-PROBNP CONCENTRATION AND HEART RATE VARIABILITY, ARRHYTHMIA IN PATIENTS WITH CHRONIC ISCHEMIC HEA
Trang 1MILITARY MEDICAL ACADEMY
DOAN THINH TRUONG
RESEARCH ON THE RELATIONSHIP BETWEEN PLASMA NT-PROBNP CONCENTRATION AND HEART RATE VARIABILITY, ARRHYTHMIA IN PATIENTS WITH CHRONIC ISCHEMIC HEART
DISEASE WITH HEART FAILURE
Major : Internal Medicine Code : 9720107
SUMMARY OF THE THESIS
HA NOI – 2021
Trang 2Medical Military University
Supervisor:
Prof Ph D Nguyen Oanh Oanh
Reviewer 1: Prof Ph D Nguyen Thi Bach Yen
Reviewer 2: Prof Ph D Pham Dang Khoa
Reviewer 3: Prof Ph D Luong Cong Thuc
Thesis will be defended at Sientific of Medical Military University
Trang 31 Background
The lack of blood supply to the heart muscle in chronic ischemicheart disease (CIHD) resulting in functional decline in a part of theleft ventricular myocardium, impaired left ventricular relaxation,increased stiffness, decreased diastolic filling, hypertrophy andfibrosis of the myocardium, along with the process of myocardialrestructuring are the causes leading to electrical changes of themyocardial organization, giving rise to arrhythmias and heart failure.Myocardial ischemia causes increased myocardial cell stretch,resulting in left ventricular systolic and/or diastolic dysfunction,which is an important contributor to plasma NT-proBNP release
In Vietnam, there have been many studies on the characteristics
of arrhythmia and heart rate variability (HRV) in patients withCIHD, but there have not been many studies on the relationshipbetween NT-proBNP levels and arrhythmias, HRV andcharacteristics of heart failure in these subjects Therefore, we
conducted a study on the topic " Research on the relationship between plasma NT-proBNP concentration and HRV, arrhythmia
in heart failure (HF) patients with CIHD" with two objectives:
1 To investigate the changes in plasma NT-proBNP concentrations and characteristics of arrhythmias, HRV in HF patients with CIHD before and after 7 days of inpatient treatment.
2 To explore the relationship between NT-proBNP concentration and some clinical and laboratory characteristics, HRV and arrhythmia in HF patients with CIHD.
2 The rationale of the thesis
Trang 4HRV and arrhythmia are common cardiovascular events andcause many serious consequences Does the presence of arrhythmiasand HRV depend on NT-proBNP levels? Many previous studiesshowed the correlation between HRV, arrhythmia and NT-proBNPconcentration However, these studies were performed in patientswith myocardial infarction and unstable angina Thus, a question israised whether there is a correlation between NT-proBNPconcentration and HRV, arrhythmia in HF patients with CIHD ornot? The studies on this topic are very scarce In Vietnam, there hasbeen no study to fully evaluate the relationship between plasma NT-proBNP level and HRV, arrhythmias in HF patients with CIHD.Therefore, this research is to find a solution for the above-mentionedscientific and practical problem.
3 New contributions of the thesis
Time domain HRV parameters (SDNN, RMSSD, SDNNI) andfrequency domain HVR (LF, HF, LF/HF) among HF patients withCIHD showed this condition continued to increase, independent ofbaseline NT-proBNP (p < 0.05)
4 Structure of the dissertation
The thesis has 127 pages, including the following parts:Introduction (02 pages); Overview (30 pages); Research subjects andmethods (24 pages); Results (31 pages); Discussion (36 pages);Conclusion (02 pages); Recommendations (01 page) The thesis has
57 tables, 06 charts, 05 pictures The thesis has 189 references,including 26 Vietnamese documents and 163 English documents
CHAPTER 1: GENERAL OVERVIEW 1.1 Chronic ischemic heart disease and heart failure
Trang 5CIHD is a disease related to the relative stability of coronaryatherosclerotic plaque, when there is no sudden rupture or after theacute phase or after intervention/surgery When the plaqueprogresses leading to significant luminal narrowing of the coronaryarteries (usually more than 70% of the lumen diameter), symptomscan occur, most notably angina/dyspnea on exertion and thesesymptoms disappear at rest
The mechanism of heart failure caused by ischemic heart disease
is simply summarized below, including the following mainphenomena:
- Myocardial infarction/re-myocardial infarction: Cardiac musclecell death and fibrosis, scarring => remodeling and activation ofhomeostatic factors
- Anemia: Decreased function of one region of the left ventricularmyocardium; left ventricular relaxation disorder, increased stiffnessdecreased diastolic filling
1.2 Arrhythmias and heart rate variability
1.2.1 Cardiac arrhythmias in CIHD and heart failure
Cardiac arrhythmias is usually caused by disorders of impulseformation and/or impulse conduction These disturbances appear due
to a single or combined mechanism, sometimes the arrhythmia can
be initiated by one mechanism but perpetuated by others Thedisturbance of impulse formation is a disorder of theheart's natural pacemaker (sinus node) that causes a slow or fast heartrate, or due to the pacemaker activity The mechanism of cardiacarrhythmia are generally divided into 2 major categories:
- Automaticity: Enhanced normal automaticity, Abnormalautomaticity, Triggered activity
Trang 6- Reentrant arrhythmias: Cardiac arrhythmias due to impulseconduction disturbance are often associated with a reentrant loopmechanism.
1.2.2 Heart rate variability in chronic ischemic heart disease
Analysis of HRV by conventional time and frequency domainmethods has offered a novel approach for studying the abnormalities
in cardiovascular neural regulation in ischemic heart disease HRVhas been shown to be altered among patients with ischemic heartdisease as compared with their age-matched controls withoutevidence of ischemic heart disease There were also obviousdifferences in various measures of HRV between patients withuncomplicated coronary artery disease and those with coronaryartery disease complicated with myocardial infarction ReducedHRV predict an increased risk of death and cardiovascular events inpatients with ischemic heart disease In particular, recent studieshave shown that analysis methods of HRV predict the mortality andthe onset of life-threatening arrhythmias in post-myocardialinfarction patients These findings support the notion that HRVanalysis methods give valuable clinical information among patientswith ischemic heart disease patients with ischemic heart disease
1.3 Research on the association between NT-proBNP and chronic ischemic heart disease, heart failure, arrhythmia and Heart rate variability.
Rosenberg M.A et al (2014) “N-pro-B-type natriuretic peptide(NT-proBNP) or B-type natriuretic peptide (BNP) is an independentpredictor of ventricular arrhythmias in patients receiving primaryprevention ICD” In a multivariate analysis on 161 patients with NT-proBNP levels and 403 patients with BNP levels at the time of ICD
Trang 7implantation The results showed that elevated NT-proBNP and BNPconcentrations were independently associated with risk of ventriculartachyarrhythmias, which significantly exceeds the risk for totalmortality.
Solbiati M (2014): “The usefulness of N -terminal pro - B-typenatriuretic peptide increase as a marker of cardiac arrhythmias inpatients with syncope” The results showed that increase in the 6-hour NTproBNP concentration can predict arrhythmic syncope.Patton K.K et al (2013) “NT-pro BNP is a remarkably strongpredictor of atrial fibrillation (AF) event in the Multiethnic Study ofAtherosclerosis: the effects of age, sex and ethnicity" The studyinvolved 5.518 subjects with a median follow-up of 7.6 years Theresults show that NT-proBNP is a robust predictor of incident atrialfibrillation; its prognostic value is more significant in youngerpatients and women compared with older patients and men NT-proBNP was as strongly predictive in black patients, Hispanics, andAsian/Chinese as in white patients despite a lower incidence ofarrhythmia Many studies have demonstrated that NT-proBNP isincreased in patients with atrial fibrillation
Pivatelli et al (2012) studied on 77 patients undergoing coronaryangiography, the patients were divided into 2 groups: the group withcoronary artery disease and the group without coronary arterydisease, HRV was recorded in 40 minutes The first 1000 RRintervals were selected for analysis, HRV parameters includingSDNN, rMSSD, pNN50, HF significantly decreased in patients withcoronary artery disease
Trang 8CHAPTER 2: SUBJECTS AND METHODS
2.1 Subjects
136 HF patients were diagnosed with CIHD who were treated atthe Cardiology Department, Military Hospital 103 and the InternalMedicine Department, Hanoi Heart Hospital, from April 2015 toJanuary 2021
2.1.1 Selection criteria
Patients were diagnosed with CIHD and heart failure, according
to “European Society of Cardiology 2013” and “Diagnosis andtreatment of heart failure according to ESC 2012”
2.1.2 Exclusion criteria
- Acute coronary syndrome, acute heart failure, organic valvulardisease, cardiomyopathy (dilated cardiomyopathy, hypertrophiccardiomyopathy, obstructive cardiomyopathy, alcoholic heartdisease, peripartum cardiomyopathy), congenital heart disease
- Severe acute systemic diseases, impaired liver and kidneyfunction
Patients and families did not agree to participate in the study, themedical records do not have enough data for research
2.2 Methods
2.2.1 Research design: Prospective, descriptive, cross-sectional
study with comparison pre- and post-treatment
2.2.2 Research parameters
2.2.2.1 Research on clinical features
- Age, gender, risk factors of the research group
- Anthropometric indicators: height, weight, BMI
- Characteristics of chest pain, symptoms and signs of heartfailure
Trang 9- Grading and stages of heart failure.
2.2.2.2 Paraclinical tests
- Blood count test, blood biochemistry: NT-proBNP, Glucose,Total cholesterol, Triglyceride, HDL-C, LDL-C, Urea, Creatinin,GOT, GPT, CK, CKMB before and after treatment
- Record 12-lead electrocardiogram, echocardiogram
- Contrast coronary angiogram to determine the location andextent of damage
- Record Holter electrocardiogram before and after treatment Average heart rate, fastest heart rate, slowest heart rate
Supraventricular arrhythmias, number and incidence ofpremature ventricular complexes (PVCs)
Ventricular arrhythmias, number and rate of prematureventricular complexes (PVCs), nature of ventricular arrhythmiasaccording to Lown's classification
+ Time-varying indices (unit: milliseconds): characterizes thetone of parasympathetic nerve system activity
SDNN: Standard deviation of all normal R-R intervals over theentire 24-hour Holter electrocardiogram Decreased when SDNN <50ms, reflecting the loss of circadian rhythm, reducing the impact ofthe CNS on heart rate
rMSSD: Square root of the mean square of the differencebetween the 24-hour Holter normal R-R intervals This value reflectsthe function of parasympathetic nervous system Decreased whenrMSSD < 15ms
SDNNi: Mean value of standard deviation of all normal R-Rintervals over all 5-minute segments of the 24-hour Holter ECG.Decrease when SDNNi < 30ms
Trang 10+ Frequency spectrum analysis indicators (unit: ms2)
TP: Total magnitude of HRV over the frequency spectrum, from0-0.4 Hz
LF: Low frequency region (0.04-0.15Hz), when increasing LFoften increases sympathetic nerve activity
HF: High frequency region (0.15-0.40Hz), when increasing HFoften increases the activity of parasympathetic nerves
LF/HF ratio: assesses the balance of sympathetic andparasympathetic nervous system activity
2.3 Data processing
Information collected from research medical records will beprocessed according to medical statistical algorithms based on thesoftware EPI DATA and SPSS 21.0 for Windows
CHAPTER 3: RESULTS
Through a study on 136 patients diagnosed with CIHDaccompanied with heart failure who were treated at CardiologyDepartment A2, Military Hospital 103 and Internal MedicineDepartment, Hanoi Heart Hospital, from April 2015 to January 2021,
we have obtained the following results:
Table 3.4 Clinical features on admission (n = 136)
Trang 11Systolic blood pressure, ( X
Mean heart rate, ( X SD) 80.89 ± 14.98 79.07 ± 12.08 <0.05
Fastest heart rate, ( X SD) 118.78 ± 28.37 118.36 ±
28.61
>0.05Slowest heart rate, ( X
SD)
57.51 ± 10.49 56.43 ± 10.39 >0.05Ventricular tachycardia, n (%) 5 (3.7) 3 (2.2) >0.05Supraventricular septic shock, n
(%)
5 (3.7) 5 (3.7) >0.05Supraventricular premature
Atrial fibrillation, n (%) 19 (14.0) 18 (13.2) >0.05Premature ventricular complexes
Table 3.20 Changes in HRV parameters on Holter ECG before and after treatment
Trang 12Two lesions (n = 28)
Three lesions
( X SD) ( X SD) ( X SD)
SDNN (ms) 56.46 28.59 35.22 20.09 20.46 16.55 < 0.05RMSSD (ms) 23.27 7.35 20.12 7.44 16.97 5.62 < 0.05SDNNi (ms) 38.33 12.72 31.31 13.23 20.95 9.64 < 0.05
TP (ms2) 1947.45
410.09
1476.34 344.29
1069.69 304.54 < 0.05
HF (ms2) 439.53
169.66
247.58 112.43
211.37 124.27 < 0.05LF/HF 2.63 0.59 3.21 0.6 3.56 0.64 < 0.05
Table 3.23 Change in HRV index on Holter ECG according to left ventricular ejection fraction (LVEF) before prior to treatment.
Trang 13NYH A
NT-proBNP (n = 136)
( X Mean ( X SD) Mea
Class I
(n = 14)
1235.3 ±4118.4 609.6
Class I(n=69)
667.4 ±1283.8
461.6
<0.05Class II
(n=55)
4552.3 ±8280.3 961.8
Class II(n=35)
1706.9 ±3173.9
571.7
<0.05
Class III
(n=43)
4167.6 ±5811.8
1222
4
Class III(n=24)
1993.5 ±2604.0
650.4
<0.05
Class IV
(n=24)
2453.2 ±2820.5
1541
5
Class IV(n=9)
1068.6 ±1044.4
1147.5
<0.05
Trang 14NT- proBNP after treatment (n =
NT-P ≥
proBN
15.63
0.45->0.05
6.8
9 0.75-6.25
>0.05
Trang 151.95-<0.0 5
Supraventricular
premature beats
29
55
8
35
Bảng 3.42 The relationship between NT-proBNP and arrhythmia on Holter after treatment
Arrhythmias
proBNP
NT-≥ 547.7 pg/ml (n = 50)
proBN
NT-P <
547.7 pg/ml (n = 86)
42
9
2.1 7
4.44
1.06-< 0.05
Supraventricula
2.68
16.62 > 0.05Atrial
0.43-fibrillation 13
26
5.8 5
17.63
1.94-< 0.05
37
2
0.94
1.95 > 0.05
0.46-Table 3.43 The relationship between the reduced HRV indexes over time and NT-proBNP level.
HRV
NT-proBNP before treatment (pg/ml)
NT-proBNP after treatment (pg/ml)
p <
0.05
1082.16 ±2165.62
p <0.05
≥ 50 ms 987.00 ± 669.5 592.99 ±