Method for prediction of developing life-threatening ventricular arrhythmias in patients with no structural cardiac changes

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely cardiology, and concerns prediction of the developing life-threatening ventricular arrhythmias in the patients with no structural cardiac changes. That is ensured by determining a blood serum interleukin 6 level by a quantitative method, and the value > 14.9 pg/ml enables predicting the developing life-threatening ventricular arrhythmias in the given category of patients.

EFFECT: method provides specifying the indications to well-timed antiarrhythmic therapy.

3 ex

 

The invention relates to medicine, namely cardiology, and can be used to predict the development of life-threatening ventricular arrhythmias in patients with ventricular extrasystoles without structural changes of the heart.

Ventricular cardiac arrhythmias rightly associated with the probability of developing fatal arrhythmias, i.e. from sudden arrhythmic death. It was proven that 75-80% of patients the cause of sudden death is ventricular fibrillation, which precede ventricular arrythmia high gradations in B.Lown and .Wolf (1971, 1983). According to J.T.Bigger, in individuals without symptoms of infarction with normal contractile function of the left ventricular extrasystole, including episodes of non-sustained ventricular tachycardia and even constantly-recurrent tachycardia, does not affect the forecast and there is no danger to life. At the same time, arrhythmia in patients without organic pathology of the myocardium subjectively poorly tolerated, worsen the quality of life and adversely affect hemodynamics. In addition, it should be emphasized that ventricular fibrillation can cause remodeling of the myocardium. Noteworthy results of a prospective observation, where it was shown that patients with ventricular arrhythmias inorganic origin increases the frequency of fuss the breath of myocardial infarction and sudden death. In this context, it is important to identify patients with high risk of sudden arrhythmic death for a more thorough investigation and timely anti-arrhythmic therapy. However, simple, informative and inexpensive methods of research, allowing you to quickly predict the development of life-threatening arrhythmias, now almost none.

A known method for predicting the development of ventricular arrhythmias in patients with ischemic heart disease by calculating the dispersion of QT intervals and JT. The authors found that with the increase in the dispersion of the QT interval more than 79 MS had an increased risk of developing life-threatening ventricular arrhythmias. However, this method reflects only one of the possible mechanisms of aristogenesis - heterogeneity of repolarization of the myocardium.

A known method for predicting adverse outcomes arrhythmic origin in patients with ischemic heart disease with myocardial scintigraphy and exercise stress echocardiography. In the course of the study revealed foci of ischemia, which is a potential source of life-threatening arrhythmias. However, these methods are not completely safe for patients (the development of ventricular fibrillation during the stress test with dobutamine), they do not reveal the initial functional changes in the myocardium and article is Nevada informative with the development of gross morphological abnormalities. In addition, these studies are expensive and can only be performed in specialized units.

A known method for predicting the development of life-threatening ventricular arrhythmias in acute alcohol intoxication (patent of Russian Federation №2272558 from 10.12.2003,). Register short sections of the electrocardiogram. Analyze high-frequency component of the spectral measure of heart rate variability and dispersion of the QT interval. Calculate the coefficient of arrhythmic risk in mathematical formula. However, this method of prediction of ventricular arrhythmias is applicable only for patients with alcohol intoxication.

Diagnostic reliability of existing predictors of ventricular arrhythmias small that motivates us to search for new markers of development conditions, life-threatening in patients without structural changes of the heart.

The disadvantages of the known methods: insufficient accuracy, the duration of the diagnostic process, the complexity of the methodology, insecurity methods are not applicable to patients without structural changes of the heart.

Methods of forecasting the development of life-threatening ventricular arrhythmias in patients with ventricular extrasystoles without structural changes of the heart in the available literature is not found.

The technical result in the possibility of accurate and fast prediction of the development of life-threatening ventricular arrhythmias in patients with ventricular extrasystoles without structural changes of the heart.

This result is achieved by the fact that patients with ventricular arrhythmias without structural changes of the heart determine the concentration of interleukin-6 in serum by the method of enzyme-linked immunosorbent assay with the use of standard test systems "IL-6-ELISA-best - VECTOR-BEST, Novosibirsk region, settlement Koltsovo). When the level of interleukin-6 less than 14.9 PG/ml predict the development neispavanog ventricular arrhythmia. When the level of interleukin 6 more than 14.9 PG/ml ventricular fibrillation is considered life-threatening.

The method is as follows: the level of interleukin-6 identify patients with ventricular arrhythmias without structural changes of the heart in blood serum by the method of enzyme-linked immunosorbent assay with the use of standard test systems.

Detection method based on solid phase "sandwich" - variant enzyme immunoassay. The analysis is performed in three stages. At the first stage of the study and control samples incubated in the wells with immobilized and antibodies. Next, the bound peroxidase interleukin 6 interacts with incubation with the conjugate, No. 1 (antibodies to interleukin No. 6 person with Biotin), unbound conjugate is removed by washing. At the third stage of bound peroxidase conjugate No. 1 interacts during incubation with conjugate No. 2 (streptavidin with horseradish peroxidase) After the third washing, the amount of bound peroxidase conjugate No. 2 determined by color reaction using the substrate of horseradish peroxidase - hydrogen peroxide and Chromogen - tetramethylbenzidine. The reaction is stopped by the addition of stop reagent and measure the optical density of the solutions in the wells at a wavelength of 450 nm. The intensity of the yellow colour developed is proportional to the number contained in the sample interlekin - 6.

The result is evaluated as follows:

The level of interleukin-6 less than 14.9 PG/ml, there is a low risk of developing zizneopisa arrhythmias (probability of a favorable outcome - 71%).

- The level of interlaying 6 more than 14.9 PG/ml, there is a high risk of adverse outcome (likelihood of developing life-threatening ventricular arrhythmias is 85%).

Examples of specific applications:

Example 1: Patient S., 46 years old, was admitted to cardiology Department of KKB Perm complaints: interruptions in heart, discomfort in precardiac region without a clear connection with physical exercise.

From the anamnesis: interruptions in heart for 2 years, discomfort in precardiac region in the last six months. In HMM-ECG within 2 years registered frequent monomorphic ventricular premature beats. Antiarrhythmic therapy is not routinely received, situational took atenolol 25 mg with positive effect.

My father at the age of 47 - sudden cardiac death.

Objectively: the patient is in satisfactory condition, BP 120/80 mm Hg, heart sounds loud, ri is m right.

In OAK: er - 4.9 million/µl; Hb - 137 g/l; Tr - 199 thousand/ál; Le - 5.1 thousand/ál (eosinophils 4%, stab neutrophils 2%, segmented neutrophils 60%, lymphocytes 27%, monocytes 7%); ESR - 11 mm/h

In the biochemical blood test: whole protein 78.2 g/l, glucose 4.18 mmol/l, creatinine 64.7 µmol/l, bilirubin to 12.0 mmol/l, ASAT ed/l, Alat 21.8 u/l, potassium 4.5 mmol/l

Lipid profile: total cholesterol - 5.2 mmol/l, low density lipoprotein - 3.2 mmol/l, high density lipoprotein - 1.7 mmol/l, triglycerides - 1.57 mmol/l thyroid Hormones: TSH - 1.33, mkme/ml, free T4 - 1.1 ng/DL.

ECG: sinus rhythm with the correct HR 52 minutes

Echocardiography: the root of the aorta 2.5 cm, the opening of the aortic valve 2.0 cm, pulmonary artery 1.9 cm, the CRA annuals 1.0 cm, the CRA ssli 1.1 cm, the CRA LV 4.9 cm, DAC LV 3.2 cm, FU LV 34,7%, LV EDV 112 ml, CSR LV 41 ml, PP LV 96 ml, LVEF 63,6%, the CRA mud 1.8 cm, the CRA PL 2,3 see the Conclusion: heart cavity is not expanded. Global airway maintained. Hypertrophy of the myocardium is not revealed. Kinetics and morphology of the valves without features.

HMM-EKG: while monitoring heart rate average 82 per minute (maximum 148, minimum - 56 min). Registered single ventricular extrasystoles - 4252/day, 388 per hour, including the type coupled 526/day (maximum of 112 per hour). Other LDCs, changes ST, T is not detected.

Inflammatory markers: PSA 2.1 mg/l, fibring the n 3.0 g/L. Interleukin 6-23 .5 PCG/ml, i.e. a high risk of developing innerpanel ventricular arrhythmia.

Set Ds: Idiopathic ventricular extrasystole 4A gradations in Lown. Treatment: cordarone 400 mg / day, aspirin-KARDIO 100 mg per day. The treatment condition improved outages in the heart decreased, discomfort in precardiac region not worried.

Example 2: Patient O., 38 years old, was admitted to cardiology Department of KKB Perm complaints: pain in the heart stabbing character at rest and during physical exertion, palpitations, episodes of dizziness.

From the anamnesis: raising HELL for 5 years, heart pain for 2 years. Antihypertensive therapy is not routinely received, situational took captopril 25 mg with positive effect. Episodes of palpitations and dizziness appeared in the last 3 months.

Objectively: the patient is in satisfactory condition, BP 150/90 mm Hg, heart sounds loud, the rhythm correct.

In OAK: er - 5.7 million/µl; Hb - 154 g/l; Tr - 260 thousand/ál; Le - 4.5 thousand/ál (eosinophils 2%, stab neutrophils 2%, segmented neutrophils 58%, lymphocytes 37%, monocytes 10%); ESR - 10 mm/h

In the biochemical blood test: whole protein 72 g/l, glucose 5.1 mmol/l, creatinine 77 µmol/l, bilirubin 14.0 mmol/l, ASAT 24.1 u/l, Alat 28.5 u/l, potassium 4.66 mmol/L.

Lipid profile: total cholesterol - 4.1 mmol/the, low-density lipoprotein - 2.2 mmol/l, high density lipoprotein - 1.61 mmol/l, triglycerides - 1.1 mmol/l thyroid Hormones: TSH - 1.60-mkme/ml, free T4 - 1.3 ng/DL.

ECG: sinus rhythm with the correct heart rate 70 minutes

Echocardiography: the root of the aorta 2.7 cm, the opening of the aortic valve 1.8 cm, pulmonary artery 1.7 cm, the CRA annuals 0.9 cm, the CRA ssli 0,85 cm, the CRA LV 4.2 cm, DAC LV 62 cm, FU LV 34%, LV EDV 88.9 ml CSR LV 25,1 ml, PP LV 53,7 ml, LVEF 68.1%of CRA mud of 2.18 cm, the CRA PL 3,7 see the Conclusion: heart cavity is not expanded. Global airway maintained. Hypertrophy of the myocardium is not revealed. Kinetics and morphology of the valves without features.

HMM-EKG: while monitoring heart rate average 77 per minute (maximum 174, minimum - 52 in a moment). Registered single ventricular extrasystoles - 2506/day, 181.5 per hour, including the type of bigeminy 1834/day. Other LDCs, changes ST, T is not detected.

The purpose: test against angina negative, reached a maximum heart rate of 152 per minute, HELL the maximum 170/90 mm Hg, tolerance to physical load is not reduced, the recovery period without features.

Inflammatory markers: PSA 3.81 mg/l, fibrinogen 3,15 g/L. Interleukin 6 - 10.6 PCG/ml, i.e. defined low risk of developing life-threatening ventricular arrhythmia.

Set Ds: Hypertension Art. I, 2 century AD, rice is 2. LDCs by type ventricular arrythmia 2 gradations in Lown. Treatment: Prestarium 5 mg daily, aspirin-KARDIO 100 mg per day. Antiarrhythmic therapy was not carried out. The treatment condition improved - heart pain decreased, dizziness, and palpitations are not notes, HELL normalized.

Example 3: Patient M, 48 years old, was admitted to cardiology Department of KKB Perm complaints: interruptions in the heart, constricting pain in precordial region, after intense physical exercise.

From the anamnesis: interruptions in heart for 5 years, pain in the precardiac area in the last 2 months. Not previously surveyed, treatment is not received.

Objectively: the patient is in satisfactory condition, BP 120/80 mm Hg, muffled heart sounds, regular rhythm.

In OAK: er - 4.6 million/µl; Hb - 126 g/l; Tr - 205 thousand/ál; Le - 4.1 thousand/ál (eosinophils 1%, stab neutrophils 2%, segmented neutrophils 56%, lymphocytes 29%, monocytes 8%); ESR - 7 mm/h

In the biochemical blood test: whole protein 76 g/l, glucose 5.1 mmol/l, creatinine 72.5 mmol/l, bilirubin 9.0 mmol/l, ASAT 25.1 u/l, Alat 27.1 u/l, potassium 4.7 mmol/L.

Lipid profile: total cholesterol - 4.9 mmol/l, low density lipoprotein - 2.4 mmol/l, high density lipoprotein - 1.57 mmol/l, triglycerides - 1.3 mmol/l thyroid Hormones: TSH - 1.12, mkme/ml, free T4 - 2.4 ng/DL.

ECG: rhythm is inpoly correct with 72 HR in minutes Ventricular premature beats on the type bigeminy, trigeminy.

Echocardiography: the aortic root 2.3 cm, the opening of the aortic valve 1.9 cm, pulmonary artery 1.8 cm, the CRA annuals 1.1 cm, the CRA ssli 1.0 cm, the CRA LV 4,6 cm, DAC LV 3,7 cm, FU LV 35%, LV EDV 98 ml, CSR LV 47 ml, PP LV 89 ml, LVEF of 65%, the CRA mud 2.3 cm, the CRA PL 2,1 see the Conclusion: heart cavity is not expanded. Global airway maintained. Hypertrophy of the myocardium is not revealed. Kinetics and morphology of the valves without features.

HMM-EKG: while monitoring heart rate average of 68 per minute (the maximum is 125, the minimum - 43 min). Registered single ventricular extrasystoles - 14250/day, 412/ hour, including type coupled 321/day (to a maximum of 110 per hour), bigeminy, trigeminy, 2 short paroxysm monomorphic ventricular tachycardia (5 complexes) with HR=178/min Rare single supraventricular extrasystoles. Other LDCs, changes ST, T is not detected.

Coronary angiography: Coronary artery without pathology. The type of blood circulation right. LUGA normal.

Inflammatory markers: PSA 1.5 mg/l, fibrinogen 2.8 g/L. Interleukin 6 - 46.3 PCG/ml, i.e. defined high risk of developing life-threatening ventricular arrhythmia.

Set Ds: Idiopathic ventricular extrasystole 5 gradations in Lown. Conducted antiarrhythmic treatment: cordarone 400 mg / day, aspirin-KARDIO 100 mg per day. On the background of treatment SOS is the right improved interruptions in the heart decreased, pain in precardiac region not had anticipated.

In this way were examined 80 patients in the cardiology Department of the Perm Krai clinical hospital with ventricular arrhythmias. All patients in addition to clinical examination was conducted thorough cardiac examination (ECG, Holter ECG monitoring, echocardiography, electrophysiological study on the testimony of coronaroventriculography). Obtained the following results: 33 patients (47,1%) without structural changes of the myocardium detected ventricular extrasystole high gradations in .Lown and .Wolf, there was no acute inflammatory diseases and the level of interleukin-6 in serum was >to 14.9 PG/ml (mean level 23,33±11,83 PG/ml). In these patients, ventricular arrhythmia was regarded as life-threatening, and conducted anti-arrhythmic therapy. 47 patients (52,9%) without structural changes of the myocardium diagnosed with ventricular premature beats high gradations in B.Lown and .Wolf, there was no acute inflammatory diseases and the level of interleukin-6 in serum ranged from 0.2 to 14.6 PG/ml (average 5.26±4.8 PG/ml). In this case, ventricular arrhythmia believed neispovedimy and antiarrhythmic therapy was not performed. The comparison group comprised the or 20 practically healthy people, comparable with major groups by age and gender composition, and the level of interleukin-6 in serum was in the range of from 0 to 10.2 PG/ml (mean level 4,63±of 2.51 PG/ml). For interleukin-6 was obtained split point, she was 14.9 (for this value was observed optimal ratio sensitivity 86,7 and specificity of 88.6).

The positive effect of the claimed method consists in the following: the method is highly sensitive, specific, technical; allows to predict the development of life-threatening ventricular arrhythmias in patients with ventricular extrasystoles without structural changes of the heart, thereby to provide adequate medical tactics; high performance; high availability; ease of implementation research and analysis of the results.

The proposed method can be applied as a method for the selection of patients requiring active anti-arrhythmic therapy.

A method for predicting the development of life-threatening ventricular arrhythmias in patients without structural changes of the heart, which consists in the fact that patients with ventricular arrhythmias without structural changes of the heart determine the level of interleukin-6 in serum quantitative method, and its value>to 14.9 PG/ml predict the development of life-threatening ventricular arrhythmias.



 

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