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16ЭФФЕКТИВНЫЕ МЕТОДЫ ЛЕЧЕНИЯ И АКТУАЛЬНОСТЬ КАРДИОМИОПАТИИ
Носиров Махамаджон
Андижанский государственный медицинский институт
Кардиомиопатия - это термин, обозначающий заболевания сердечной мышцы. Их также иногда называют просто увеличенным сердцем. У людей с этими заболеваниями очень большое, толстое или твердое сердце. Их сердца не могут перекачивать достаточно крови. Если не лечить, кардиомиопатия ухудшится. Они могут привести к сердечной недостаточности и нарушению сердечного ритма. Кардиомиопатия иногда может быть наследственной, но также может быть вызвана высоким кровяным давлением, диабетом, ожирением, нарушениями обмена веществ или инфекциями. В статье мы подумаем об актуальности этого заболевания и новых методах его лечения.
Ключевые слова: Кардиомиопатия, сердечная недостаточность, ритм сердца, повышенное артериальное давление, диабет, ожирение, нарушения обмена веществ, инфекции.
KARDIOMIYOPATIYANING SAMARALI DAVOLASH USULLARI VA DOLZARBLIGI
Kardiomiopatiya bu yurak muskullarining kasalliklari uchun atama hisoblanadi. Ular ba'zan oddiygina kengaygan yurak deb ham ataladi. Bunday kasalliklarga chalingan odamlarning yuraklari juda katta, qalin yoki qattiq holatda bo'ladi. Ularning yuraklari qonni kerakli darajada haydab bera olmaydi. Davolash muolajalari olib borilmasa, kardiyomiyopatiya yomonlashadi. Ular yurak yetishmovchiligiga va yurak ritmining buzilishiga olib kelishi mumkin. Kardiyomiyopatiya ba'zan irsiy paydo bo'lishi mumkin, ammo u yuqori qon bosimi, diabet, semizlik, metabolic kasalliklar yoki infektsiyalardan ham kelib chiqishi mumkin. Maqolada ushbu kasallikning dolzarbligi va uni davolashning yangi metodlari haqida fikr yuritamiz.
Kalit so'zlar: Kardiomiopatiya, yurak yetichmovchiligi, yurak ritmi, yuqori qon bosimi, diabet, semizlik, metabolic kasalliklar, infektsiya.
EFFECTIVE TREATMENT METHODS AND RELEVANCE OF CARDIOMYOPATHY
This is the term for diseases of the heart muscle. They're sometimes simply called enlarged heart. People with these conditions have hearts that are unusually big, thick, or stiff. Their hearts can't pump blood as well as they should. Without treatment, cardiomyopathy_get worse. They can lead to heart failure and abnormal heart rhythms.Cardiomyopathy may sometimes run in families, but it can also be caused by high blood pressure, diabetes, obesity, metabolic diseases, or infections.In the article we will think about the relevance of this disease and new methods of its treatment.
Keywords: Cardiomyopathy, heart failure, heart rhythm, high blood pressure, diabetes, obesity, metabolic disorders, infection.
Introduction: Cardiomyopathy is a disease of the heart muscle that makes it harder for your heart to pump blood to the rest of your body. Cardiomyopathy can lead to heart failure. The main types of cardiomyopathy include dilated, hypertrophic and restrictive cardiomyopathy. Treatment - which might include medications, surgically implanted devices,
heart surgery or, in severe cases, a heart transplant - depends on which type of cardiomyopathy you have and how serious it is.
Also this article will review recent developments in pharmacotherapy, procedural techniques, and gene-based therapies (Figure 1).
Figure 1. Novel therapeutic targets in hypertrophic cardiomyopathy. (Left) Novel procedural approaches target cardiac structural abnormalities in hypertrophic cardiomyopathy. (Middle) Novel pharmacotherapies target abnormal cellular processes in hypertrophic cardiomyopathy. (Right) Allele-specific gene silencing and genome editing using CRISPR/Cas9 target the genetic underpinnings of hypertrophic cardiomyopathy. ARB, angiotensin II receptor blocker; LV, left ventricular; LVOT, left ventricular outflow tract; SAM, systolic anterior motion.
End-stage (ES) hypertrophic cardiomyopathy (HCM) has been considered a particularly grim and unfavorable disease complication, associated with substantial morbidity and mortality, frequently requiring heart transplant. According to conclusions which are belong to group of some scientists [1], Although ES remains an important complication of HCM, contemporary treatment strategies, including ICDs and heart transplant, are associated with significantly lower mortality than previously considered. Primary prevention ICDs should be considered when EF is <50% in HCM. Rapid heart failure progression is not an inevitable consequence of ES, and some patients experience extended periods of clinical stability.
Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic disorder most often caused by sarcomeric mutations resulting in left ventricular hypertrophy, fibrosis, hypercontractility, and reduced compliance. It is the most common inherited monogenic cardiac condition, affecting 0.2% of the population. Whereas currently available therapies for HCM have been effective in reducing morbidity, there remain important unmet needs in the treatment of both the obstructive and non-obstructive phenotypes. Novel pharmacotherapies directly target the molecular underpinnings of HCM, while innovative procedural techniques may soon offer minimally-invasive alternatives to current septal reduction therapy. With the
advent of embryonic gene editing, there now exists the potential to correct underlying genetic mutations that may result in disease.
Some group scientists [2] say that hypertrophic cardiomyopathy is a complex cardiac disease with unique pathophysiologic characteristics and a great diversity of morphologic, functional, and clinical features. The heterogeneity of the disease is accentuated by the fact that it afflicts patients of all ages. During the past few years, technological developments in implantable defibrillators and pacemakers have provided new therapeutic options for patients with the disease. In addition, rapid advances in our knowledge of the molecular defects responsible for hypertrophic cardiomyopathy have deepened our understanding of the disorder and have suggested new approaches to the assessment of prognosis. These recent developments, however, have also generated considerable uncertainty and raised new questions about the optimal management of hypertrophic cardiomyopathy.
Another group of scientists is of the opinion that, the main conclusion is that patients with rCS-complicating PPCM appear to benefit from mechanical cardiac unloading with a high 30-day survival rate of 100%. This applies to PPCM patients with isolated LV failure and LV-unloading with the Impella CP as well to those with biventricular failure and combined support with the Impella CP and VA-ECMO. MCS allowed for recovery of systolic function in two patients and bridge to LVAD in three patients. However, one patient suffered from overwhelming sepsis and died after explantation of the permanent LVAD after myocardial recovery 131 days after hospital admission. MCS obviously counteracted the severe shock status of our patients, as the CARDShock risk score [3 ] and SAVE score [4] predicted a mortality of 36% and 42%, respectively. The Impella CP is a promising device for isolated LV failure in CS. [5] The Impella micro-axial pump unloads the left ventricle, thereby reducing LV end diastolic pressure, LV wall tension and myocardial oxygen consumption. Moreover, pulmonary capillary pressure routinely decreases on Impella support. [6,7] VA-ECMO is increasingly used in the treatment of CS to support oxygenation and maintain circulation. [8] However, retrograde blood flow from the arterial ECMO cannula results in increased LV afterload, distension of the left ventricle, thrombus formation and pulmonary congestion in patients with impaired LV function. Thus, the combination of the Impella and VA-ECMO is promising to prevent LV deterioration and to maintain perfusion and oxygenation in biventricular failure, hypoxaemia and intractable CS. Previously published data in patients with rCS indicate that biventricular unloading is feasible. They concluded their research with the following conclusions [9 ], mechanical circulatory support in patients with refractory cardiogenic shock complicating peripartum cardiomyopathy was associated with a 30-day survival of 100% and a favourable outcome. Notably, early left ventricular unloading combined with bromocriptine therapy was associated with left ventricular recovery. Therefore, an immediate transfer to a tertiary hospital experienced in mechanical circulatory support in combination with bromocriptine treatment seems indispensable for successful treatment of peripartum cardiomyopathy complicated by cardiogenic shock.
There are few opinions about the disease. Recent observations suggest that the prevalence of hypertrophic cardiomyopathy in the general population is higher (about 1 in 500) than previously thought. [10] The condition therefore appears to be a common genetic malformation of the heart. The clinical course varies markedly; some patients remain asymptomatic throughout life, some have severe symptoms of heart failure, and others die suddenly, often H in the absence of previous symptoms. The heterogeneous natural history of the disease and the fact that patients with severe symptoms are preferentially referred to tertiary care centers have been major impediments to assembling large study populations that truly represent the overall spectrum of the disease. Indeed, because most of the literature on hypertrophic cardiomyopathy is derived from investigations performed at tertiary care
centers, the clinical picture of the disease that has emerged from published studies is profoundly influenced by referral bias. [11-16] This is evident in the fact that the annual mortality figures for hypertrophic cardiomyopathy from such institutions (3 to 4 percent overall and up to 6 percent in children) [17-19] are substantially higher than those recently reported in unselected populations (1 percent or less). [11-16] These observations suggest that in a substantial proportion of patients the disease has a more favorable clinical course than previously believed.
Figure 2. Components of the Sarcomere.
Cardiac contraction occurs when calcium binds the troponin complex (subunits C, I, and T) and a-tropomyosin, making possible the myosin-actin interaction. Actin stimulates ATPase activity in the globular myosin head and results in the production of force along actin filaments. Cardiac
myosin-binding protein C, arrayed transversely along the sarcomere, binds myosin and, when phosphorylated, modulates contraction. In hypertrophic cardiomyopathy, mutations may impair
these and other protein interactions, result in ineffectual contraction of the sarcomere, and produce hypertrophy and disarray of myocytes. Percentages represent the estimated frequency with which a mutation on the corresponding gene causes hypertrophic cardiomyopathy.
Modified from Seidman and Seidman.
Strategies for treatment should therefore rely on data from relatively unselected populations, as well as from studies at tertiary care referral centers, and on the clinical experience of physicians who have focused their investigative efforts on this disease and acquired particular expertise in its management. Molecular studies of the genetic alterations responsible for hypertrophic cardiomyopathy also provide insight into the heterogeneity of its clinical features. The disease can be caused by a mutation in one of four genes that encode proteins of the cardiac sarcomere: the b-myosin heavy-chain, cardiac troponin T, a-tropomyosin, and myosin-binding protein C genes (Figure 2). [20-23] In addition, mutations
in the two genes encoding the myosin light chains have been reported in what appears to be a rare form of hypertrophic cardiomyopathy,38 and other genes that cause the disease are likely to be found. [24] This etiologic complexity is further compounded by intragenic heterogeneity; more than 50 disease-causing mutations have been identified in these genes of the sarcomere. Hence, the precise molecular defect responsible for hypertrophic cardiomyopathy often differs in unrelated patients. The diverse clinical and genetic features of hypertrophic cardiomyopathy make it impossible to define precise guidelines for management. As in many diseases, it is often necessary to individualize therapy. In hypertrophic cardiomyopathy, the treatment of symptoms to improve quality of life and the identification of patients who are at high risk for sudden death and require aggressive therapy are two distinct issues that must be addressed by largely independent strategies.
Pharmacologic therapy to improve diastolic filling and possibly reduce myocardial ischemia is the primary means of relieving symptoms in hypertrophic cardiomyopathy; it is also the sole therapeutic option for patients without obstruction of the left ventricular outflow, who constitute the great majority of patients with this disease. Invasive interventions to abolish the outflow gradient should be considered only for the minority of patients (about 5 percent) who have both marked outflow obstruction and severe symptoms unresponsive to medical therapy.
Patients with symptomatic oHCM are generally offered first-line pharmacotherapy with ^-blockers or the non-dihydropyridine calcium-channel blockers. [25-27] Disopyramide is effective as an add-on therapy, although it can be poorly tolerated. These medications have been the mainstay of treatment for decades and share in common their negative inotropic effect resulting in reduction of SAM/septal contact and LVOT obstruction. Despite their utility, current guideline-directed pharmacotherapies were never designed for the treatment of HCM and have limited evidence. In fact, there have been no randomized trials that demonstrate the efficacy of any agent over placebo in HCM, [28] and currently propranolol is the only Food and Drug Administration-approved drug based on a small study from 1966. [29] Moreover, nonobstructive HCM (noHCM), representing ~30% of HCM, remains poorly addressed with no known disease-modifying therapies. Recent evidence has also demonstrated important gender differences in HCM, with women being older and more symptomatic at presentation, and perhaps having lower survival when compared to men.
Tuohy, C. V., Kaul, S., Song, H. K., Nazer, B., & Heitner, S. B. gave own conclusions in own article [30]: Despite tremendous strides in improving care for patients suffering from HCM, there remains a significant burden of disease. In recent years, we have seen the emergence of novel pharmacotherapies, minimally-invasive procedures, and gene-directed approaches with the potential to fundamentally alter the therapeutic landscape. While most recent drug trials have failed, they have advanced our understanding of therapeutic targets, and there is promise for the myosin inhibitors. Surgical techniques continue to evolve and now frequently address the mitral valve, while novel procedures including transcatheter mitral valve repair, RF myocardial ablation, and HIFU may soon offer alternatives for patients with oHCM. Looking to the distant future, there is even the potential to address the very genetic mutations responsible for the disease and prevent transmission to future generations. We believe that this blossoming field offers tremendous opportunities for young investigators and clinicians working to improve quality of life for patients with HCM. Conflict of interest: S.B.H. has received research and consulting funding from MyoKardia Inc. and Cytokinetics Inc.; and he serves as co-chair on the Steering Committee for the EXPLORER-HCM study. The other authors have nothing to disclose. Certainly, we also agree with their opinions and we support it.
As for as some group scientists go said [31] that the management of VT/VF to prevent SCD after myocardial infarction remains challenging and calls for novel mechanistic-based non-invasive treatment. Identification of the arrhythmia critical sites and characterisation of the molecular signature unique to these sites can open avenues to targeted therapy and reduce off-target effects that have hampered systemic pharmacotherapy. Such advances are in line with precision medicine and a patient-tailored therapy. In addition, there are extra conclusions [32]. The last 60 years has brought unimaginable advances in our understanding of HCM. Only recently, however, drug development has started to exploit available knowledge and to provide innovative molecules addressing specific mechanisms of disease. In all likelihood, the present decade will witness a paradigm shift in targeted management of HCM patients, with implication potential reaching other fields of cardiovascular medicine overlapping this complex disease.
Conclusion: In conclusion, in this article we have reviewed the current status of cardiomyopathy. We also discussed the treatment options for this disease. We have analyzed the opinions and conclusions of several scientists on this topic. We believe that this article can be an impetus for further in-depth research.
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