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11результатов прижизненной диагностики и посмертной визуализации органа.
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CONNECTIVE TISSUE DYSPLASIA IN THE ASPECT OF SUDDEN CARDIAC DEATH
Smetanin M.
candidate of medicine, Republican Clinic and Diagnostics Center, Izhevsk
Russian Federation
Pimenov L.
doctor of medicine, Izhevsk State Medical Academy
Russian Federation Chernyshova T.
doctor of medicine, Izhevsk State Medical Academy
Russian Federation
Abstract
Sudden cardiac death (SCD) is an actual problem of the world medical practice nowadays. The analysis of young people sudden death cases shows that connective tissue dysplasia (CTD) is one of the vessel wall pathology reasons in that patient category. Without distinction of disease leading to SCD, its main mechanism is arrhythmic. The review considers the up-to-date view on the SCD reasons under well-defined monogenic hereditary disorders of connective tissue such as mitral valve prolapse (MVP) and Marfan syndrome. It is shown that in case of MVP the immediate cause of sudden death is probably ventricular tachyarrhythmia (ventricular fibrillation) while in case of Marfan syndrome the reason is aortic dissection and disruption. SCD prevention techniques in patients with CTD are timely detection of vascular malformation and clinically significant arrhythmias.
Keywords: sudden cardiac death, connective tissue dysplasia, mitral valve prolapse, variance of the QT interval, Marfan syndrome, ventricular fibrillation, prevention.
Sudden cardiac death (SCD) is currently understood as a natural death associated with cardiac causes, preceded by sudden loss of consciousness and occurring within one hour of a change in the patient's condition or the appearance of the first clinical symptoms; the patient may suffer from heart disease, but the time and nature of death are unexpected; or death that occurred without witnesses, but if the patient is known to have felt well in the last 24 hours [21]. Most often, SCD occurs due to ventricular fibrillation (VF),
in some cases, VF is preceded by ventricular tachycardia (VT). Asystole initially develops much less often; with the onset of SCD, its probability increases, since it transforms the VF; bradiarrhythmias, as the causes of SCD, are rare [3; 5].
The frequency of SCD varies significantly for different regions. In the United States, it is estimated at 300,000-400,000 cases per year (13% of all deaths from natural causes). In Europe, this figure is 18.5%, but in Europe and Russian Federation, SCD refers to
death occurring within 24 hours of the onset of symptoms, unlike in the United States, where the time period is one hour. The prevalence of SCD in the general population is 1-2 cases per 1000 cases (i.e. 0.1-0.2% per year). In Russian Federation, according to some authors, this figure is from 0.8 to 1.6 per 1000 people per year [4; 6]. The probability of SCD is significantly higher in men compared to women (in the menopausal period). This is mainly due to the fact that the main cause of SCD is coronary heart disease (CHD): approximately 50% of deaths in CHD occur suddenly. Regardless of the disease that led to the development of SCD, its main mechanism is arrhythmic. In 75-80% of cases, this is ventricular fibrillation, in 15-20% -various bradiarrhythmias, including high-grade atrioventricular block and asystole [6; 16].
Long-term observations and research of sudden death cases show that in 75-80% of cases, the basis of diseases of the cardiovascular system (CVS) is atherosclerotic damage of large and medium-sized vessels, leading to stenosis, obstruction, as well as venous damage with the development of thrombotic complications [11; 13]. However, the analysis of cases of SCD in young people (up to 39 years old), which in recent years have tended to increase, has shown that among other causes of SCD, a significant number of cases prevail, due exclusively to vascular pathology of various calibers, associated with a violation of the development of the vascular wall, leading to the formation of aneurysms of various types and structures [1; 2; 10]. The main cause of vascular wall pathology in young people is connective tissue dysplasia (CTD), which manifests itself as a pathology of the elastic framework of vessels. In the literature, there are indications of damage to the elastic structures of the vascular wall and the transformation of the resistive nature of the arterial vessel into a capacitive one [8; 12; 14]. Most aspects of SCD in CTD are poorly understood. There is only data on the frequency of SCD in clearly defined monogenic hereditary connective tissue disorders (HCTD), such as Marfan syndrome and mitral valve prolapse (MVP) [7].
According to E. V. Zemtsovsky, the problem of SCD should be considered from the standpoint of the existence of specific monogenic HCTD and dysplastic syndromes and phenotypes (DSAF), the latter include MVP, marfanoid appearance (MA), marfan-like, Eh-lers-like, mixed and unclassifiable phenotypes and joint hypermobility syndrome [6; 7; 9]. The main cause of SCD in patients with Marfan syndrome and a number of related HCTD is aortic dissection and rupture. Electrical instability of the myocardium often causes SCD in a variety of hereditary diseases, which include arrhythmogenic cardiomyopathy, right ventricular dysplasia, pre-arousal syndromes and various hereditary channelopathies, manifested by the known syndromes of elongated or shortened QT, Brugad syndrome, etc. [7; 18].
In MVP syndrome, signs of violations of myo-cardial electrogenesis, pre-arousal phenomena, signs of involvement of the skeletal system, skin and joints are very often detected [16], which indicates the need for a detailed analysis of the causes of SCD in each
specific clinical case. SCD is a rare complication of MVP, occurring in less than 0.2% of cases during long-term follow-up, with an annual mortality rate of less than 0.1%, which corresponds to that in the general population [7]. According to the guidelines for managing patients with ventricular arrhythmias and preventing SCD [16], MVP is generally not life-threatening, and its Association with SCD has never been conclusively shown. Prognostically unfavorable factors are: the presence of cases of SCD in the patient's family, fainting, pathological changes on the ECG at rest, prolongation of the QT interval and ventricular extrasystole, episodes of VT, the presence of elongated and myxomatous damaged mitral valve leaflets [3; 18]. MVP was the only heart pathology in 10 percent of patients who died suddenly at a young age. In most patients, MVP is characterized by a favorable course. Its presence is taken into account only in the case of surgical interventions that are combined with a high risk of bacteremia and the occurrence of infectious endocarditis (IE), which causes the appointment of antibiotic therapy. In the presence of symptoms (palpitations, heart failure, feeling of lack of air), beta-blockers are usually prescribed. According to experts, they can be used for long-term treatment of patients with an increased risk of sun. For patients who have undergone resuscitation due to VF or VT, implantable cardioverter-defibrillator (ICD) is recommended for secondary prevention [5; 23].
Ventricular tachyarrhythmia is probably the direct cause of SCD in MVP - there are published data on a higher frequency of complex ventricular arrhythmias during daily ECG monitoring in suddenly deceased patients with MVP, and in some patients the QT interval was prolonged [15; 19]. However, the question of what exactly is the substrate for the occurrence of malignant ventricular arrhythmias leading to SCD in MVP remains unclear. Valvular pathology itself is unlikely to cause ventricular arrhythmias, but it can contribute to their occurrence due to its effect on the myocardium [7; 16]. According to the ESC guidelines for SCD, the risk stratification of SCD in MVP is based on the following criteria: history of cardiac arrest or VT (class I), excess myxomatous leaflets, family history of SCD, QT interval and QT variance, frequent or complex ventricular arrhythmias, mitral regurgitation (class II, level of evidence: C) [23]. Special subgroups of MVPs with a high risk of developing SCD deserve the most attention. These should include patients with severe mitral insufficiency caused by the flailing leaflet of the mitral valve - a menacing complication of MVP that significantly affects the prognosis. According to F. Grigioni et al. [20] out of 348 patients over a ten-year follow-up period, 25 died suddenly. The frequency of sudden death was 1.8% per year, and its predictors according to multivariate analysis were: NYHA functional class, left ventricular ejection fraction, and the presence of atrial fibrillation. Surgical correction of mitral insufficiency in 186 of 348 patients resulted in a significant reduction in the risk of SCD. However, the official position of the ACC/AHA/ESC is as follows: the effectiveness of mitral valve repair or prosthetics to re-
duce the risk of SCD in patients with PMC, severe mitral regurgitation and serious ventricular arrhythmias has not been established (class lib, level of evidence: C) [16; 23].
The main cause of SCD in patients with Marfan syndrome and a number of related HCTD is aortic dissection and rupture [7]. It is known that about 1-2% of fatal cases are associated with rupture and dissection of the aorta [22]. At the same time, patients with aortic rupture on the background of various HCTD make up no more than 7% of the total number of patients with aortic dissection [24]. With a seemingly small number of patients, in the United States alone, the number of cases of SCD due to aortic dissection and rupture against the background of connective tissue diseases is about 3,500 per year. Patients with Marfan syndrome have a higher mortality rate for aortic dissection compared to other patients (40% for Marfan syndrome and 21% overall for aortic dissection). In addition, aortic dissection in such patients occurs on average at the age of 27 years, and may be the first complication of this disease. Traditionally, the indication for surgery in patients with a wide aorta is the size of the aorta more than 55 mm, but in patients with Marfan syndrome and related diseases, aortic dissection may occur at a smaller size. That is why it is so important to timely identify patients with a high risk of aortic dissection and refer them for surgery [7].
In accordance with the latest recommendations of the European society of cardiology (ESC) on the management of patients with hereditary heart diseases, several indications for cardiac surgery in patients with Marfan syndrome have been identified. A patient with Marfan syndrome should be referred for surgery if the size of the aorta at the level of the Valsalva sinuses is more than 50 mm. If the size of the aorta is 46-50 mm, the patient should be recommended for surgery if there is a family history of aortic dissection, progressive aortic dilation of 2 or more mm per year, severe aortic or mitral regurgitation, or planned pregnancy. If other parts of the aorta are more than 50 mm, the patient should be further examined by a cardiac surgeon to determine the indications for surgical treatment. All patients with Marfan syndrome should undergo dynamic monitoring, including echocardiography [17].
In a number of our works we have evaluated the relationship of the QT interval variance with the degree of MVP ant with the thickness of the mitral leaflets in the aspect of SCD. 105 patients with MVP (average age was 25,0±6.5 years) were examined. An-thropometric and phenotypic studies were also conducted. The QT interval was measured using a standard method, on a 12-channel cardiograph. Echo-cardiography was performed in 2D, Doppler and M modes. MVP was diagnosed at maximum systolic displacement of the mitral valve leaflets beyond the line of the mitral ring by more than 2 mm. The thickness of the mitral leaflets flaps was measured in diastole, in their middle part, outside the chord attachment zone. The patients were divided into 3 equal in size groups depending on the degree mitral valve leaflets prolapse. The data was presented as an average value ± standard deviation. The normality of the distribution
of analyzed data was evaluated according to the Kol-mogorov-Smirnov criterion. To evaluate differences between groups we used the method of one-way dispersion analysis (p<0.05). We have obtained the following conclusions: 1) In patients with a higher degree of mitral valve prolapse and the thickness of the mitral leaflets there were increased values of QT interval variance (predictors of myocardial electrical instability, pathogenetic associated with mechanisms of sudden cardiac death). Echocardiographic assessment of the severity of mitral valve prolapse and mitral regurgitation helps to identify a group of patients with an increased risk of developing of life threatening arrhythmias and sudden cardiac death [25-28].
Summary
Thus, the main methods of preventing SCD in patients with DST should be the timely detection of vascular abnormalities (primarily, aortic dilation, followed by surgical correction according to indications), as well as clinically significant arrhythmias. It is also necessary to identify high-risk groups among these patients and actively monitor them dynamically, prescribe medication for prevention and, if indicated, implantation of cardioverter defibrillators.
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