Ассоциации полиморфных вариантов rs2305619 и rs3816527 гена пентраксина-3 (PTX3) с особенностями клинического течения и исходов у пациентов с гипертрофической кардиомиопатией: результаты 11-летнего наблюдения.

The objective of this study was to determine the association of polymorphic variants rs2305619 and rs3816527 of the PTX3 gene with clinical profile and outcomes in hypertrophic cardiomyopathy (HCM) patients.Methods and materials. The study population consisted of 153 patients ≥18 years old with a confirmed diagnosis of HCM. The control group included 200 healthy donors. Duration of follow-up was 11 years (2008–2019 yrs.). The study design included a new model for determining variants of the clinical profile and outcomes of HCM. Polymorphic variants rs2305619 and rs3816527 of the PTX3 gene were genotyped by polymerase chain reaction.Results. The mortality rate in patients ≥18 years old with 1, 2 and 3 adverse pathways of HCM progression was significantly higher, compared with those without adverse pathways (р<0.001). A combination of chronic heart failure (CHF) with midrange and reduced LVEF (<49 %) with 1, 2 and 3 adverse pathways in HCM patients occurred more frequently, compared with those who had CHF with preserved LVEF (≥50 %) (odds ratio (OR) = 0.168, 95 % confidence interval (CI) =0.068–0.412, р<0.001). The genetic testing showed no significant differences in genotype and allele frequencies of polymorphic variants rs2305619 and rs3816527 of the PTX3 gene in patients with HCM and control groups. It was found a tendency for increase in GG genotype frequency (p<0.068) and significant increase in G allele frequency of rs2305619 of the PTX3 gene in HCM patients ≥18 years old and CHF with mid-range and reduced LVEF (<49 %) (A:G, OR=0.521, 95 % CI=0.301–0.902, p<0.019). HCM patients (age – 63 [58; 75] years) and type 2 diabetes mellitus demonstrated high prevalence in AG and GG genotypes (p<0.008) and G allele frequencies of rs2305619 of the PTX3 gene (A:G, OR =1.952, 95 % CI=1.076–3.542, p<0.026).Conclusions. HCM progression along 1 and more adverse pathways in patients ≥18 years old has been characterized with adverse outcome. G allele of rs2305619 of the PTX3 gene is associated with CHF with mid-range and reduced LVEF (<49 %) in HCM patients ≥18 years old. The associations of G allele and AG and GG genotypes of rs2305619 of the PTX3 gene with diabetes type 2 are observed in elderly HCM patients.Цель – изучить ассоциации полиморфных вариантов rs2305619 и rs3816527 гена пентраксина-3 (PTX3) с особенностями клинического течения и исходов у пациентов с гипертрофической кардиомиопатией (ГКМП).Методы и материалы. В исследование (2008–2019) включены 153 пациента в возрасте ≥18 лет с подтвержденным диагнозом ГКМП. Группу контроля составили 200 практически здоровых человек. Дизайн исследования включал в себя новую модель определения вариантов клинического течения и исходов ГКМП. Полиморфные варианты rs2305619 и rs3816527 гена PTX3 были идентифицированы методом полимеразной цепной реакции.Результаты. У пациентов с ГКМП в возрасте ≥18 лет при наличии одного, двух и трех путей прогрессирования заболевания смертность за 11 лет значимо превышала аналогичный показатель у пациентов с малосимптомным течением (р<0,001). Хроническая сердечная недостаточность (ХСН) со средней и сниженной фракцией выброса левого желудочка (ФВ ЛЖ) (<49 %) значимо чаще сочеталась с наличием одного, двух и трех путей прогрессирования заболевания, по сравнению с ХСН с сохраненной ФВ ЛЖ (≥50 %) (ОШ=0,168, 95 % ДИ=0,068–0,412, р<0,001). Значимых различий в распределении генотипов и аллелей полиморфных вариантов rs2305619 и rs3816527 гена PTX3 у больных ГКМП и контрольной группе получено не было. Аллель G rs2305619 гена PTX3 определялся достоверно чаще у пациентов с ГКМП и ХСН со средней и сниженной ФВ ЛЖ (<49 %), по сравнению с сохраненной ФВ ЛЖ (≥50 %) (A:G, ОШ=0,521, 95 % ДИ=0,301–0,902, p<0,019). Была определена тенденция к преобладанию генотипа GG rs2305619 гена PTX3 при наличии ХСН со средней и сниженной ФВ ЛЖ (<49 %) (p<0,068). У пациентов с ГКМП и сахарным диабетом (СД) II типа (возраст – 63 [58; 75] года) статистически значимо преобладали генотипы AG и GG (p<0,008) и аллель G rs2305619 гена PTX3 (A:G, ОШ =1,952, 95 % ДИ=1,076–3,542, p<0,026)

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

The clinical use of the MOGE(S) classification in the differential diagnosis between idiopathic hypertrophic cardiomyopathy and its phenocopies

Aim. To determine  the relation between  idiopathic hypertrophic  cardiomyopathy (HCM) and HCM phenocopies, as well as to study the etiological pattern  of HCM phenocopies in patients  of the  North-Western  region  of Russia  in different age groups.Material  and  methods. The  study  included  321  patients  with left  ventricular hypertrophy ≥15 mm according  to an echocardiography. All the necessary clinical, laboratory and instrumental  diagnostic  methods  for verification of HCM and HCM phenocopies was carried out. In the diagnosis, the MOGE(S) classification was used.Results.  At  a  young  age,   idiopathic  HCM accounts  for  92%  (n=62),  HCM phenocopies — 8% (Danon disease (n=1 (2%)), isolated cardiac  sarcoidosis (n=1 (2%)) and systemic AL amyloidosis (n=3(4%)). Idiopathic HCM is also found in the vast majority of middle-aged patients — in 85% of cases (n=86). HCM phenocopies (15%) were in isolated  cardiac  sarcoidosis (n=3 (3%)), systemic amyloidosis variants (n=12 (12%)) — AL amyloidosis with predominant cardiac injury (n=11,11%), hereditary transthyretin amyloidosis (n=1,1%). Of the 153 examined  patients  with HCM aged  ≥60 years  old, 85% (n=131) were diagnosed with idiopathic HCM. HCM phenocopies were detected in 15% of cases (n=22). In the etiological pattern  of HCM phenocopies, transthyretin  amyloidosis was  10%:  non-hereditary   transthyretin  amyloidosis  — 6%  (n  =  9),  hereditary transthyretin  amyloidosis — 4% (n=6); AL amyloidosis — 4% (n=6). In 1 patient, acromegalic  cardiomyopathy (1%) was verified. In this article, we present 3 clinical cases that demonstrate the difficulty of differential diagnosis  between  idiopathic HCM and various HCM phenocopies.Conclusion. In all age groups,  idiopathic HCM predominates. Lysosomal storage diseases classify as  rare  diseases. Isolated  cardiac  injury with amyloidosis  and sarcoidosis is widely met but less often diagnosed. We determined a high frequency of isolated cardiac injury with amyloidosis under the age of 45 years. The etiological pattern  of HCM phenocopies in the elderly is represented mainly by transthyretin cardiomyopathic  amyloidosis of hereditary and non-hereditary  variants

ОСОБЕННОСТИ КЛИНИЧЕСКОГО ТЕЧЕНИЯ ГИПЕРТРОФИЧЕСКОЙ КАРДИОМИОПАТИИ И РОЛЬ ПОЛИМОРФНЫХ ВАРИАНТОВ В ИНТРОННОЙ И ПРОМОТОРНОЙ ОБЛАСТЯХ ГЕНА АЛЬФА-ГАЛАКТОЗИДАЗЫ А

The article reflects the importance of timely diagnosis sarcomeric and non sarcomeric hypertrophic cardiomyopathy (HCM). The results of the phenotypic and genotypic screenings aimed at identifying HCM phenocopies and, in particular Fabry disease, in the structure of left ventricular hypertrophy of unknown origin in patients of the North-West region of Russia. We analyzed the influence of polymorphisms in the intronic and promoter regions of the GLA gene on clinical course and the presence of extracardiac manifestations.Отражена важность своевременной диагностики саркомерной и несаркомерной гипертрофической кардиомиопатии (ГКМП). Приведены результаты фенотипического и генотипического скринингов, направленных на выявление фенокопий ГКМП и, в частности, болезни Фабри в структуре, гипертрофии левого желудочка неясного генеза у пациентов Северо-Западного региона России. Проанализировано влияние полиморфных вариантов в интронных и промоторных регионах гена GLA на особенности клинического течения и наличие экстракардиальных проявлений

Cardiometabolic risk factors and their relationship with the interleukin-6 receptor gene polymorphism (rs2228145) in patients with hypertrophic cardiomyopathy

Aim. To analyze associations of interleukin-6 receptor gene (IL6R) polymorphism (rs2228145) with the clinical course characteristics of hypertrophic cardiomyopathy (HCM) in groups of patients with various cardiometabolic risk factorsMaterial and methods. The sample consisted of 123 patients with HCM. The age  of the included patients ranged from 18 to 91 years (59 [41; 66.5]), of whom 59 were men, 64 — women. Two age groups were identified: the first group included patients from 18 to 44 years old, the second — 45 years and older. The control group consisted of 200 people without cardiovascular diseases and other severe comorbidities.For genetic testing, DNA was isolated from peripheral blood lymphocytes. Genotyping of the IL6R gene polymorphism (rs2228145) was carried out by realtime polymerase chain reaction.Results. A significant prevalence of CC genotype of the IL6R gene polymorphism (rs2228145) was revealed in patients aged ³45 years compared with the control group, which occurred in 14,1% and 3,0% of cases, respectively (CC:AC+AA, odds ratio (OR), 0,885, 95% confidence interval (CI), 1,051-0,691, p=0,006), and insignificant prevalence of C allele in this group, which does not reach the level of significance (A:C, OR, 0,870, 95% CI, 0,427-1,02, p=0,06). The prevalence of CC genotype (15,1% vs 3,0%) and C allele (39,0% vs 29,0%) was revealed in patients with HCM in combination with hypertension (HTN) compared with the control group (CC:AS+AA, OR=0,174, 95% CI, 0,047-0,650), p=0,004); (A:C, OR=0,638, 95% CI, 0,406-1,002), p=0,05).Conclusion. The relationship between the IL6R gene polymorphism (rs2228145) and HTN in patients with HCM was confirmed. The presence of CC genotype and C allele of the rs2228145 IL6R gene polymorphism is significantly more common in patients with HCM with the disease onset ³45 years of age. The presence of CC genotype and C allele of the IL6R gene polymorphism (rs2228145) is associated with HTN in patients with HCM

GENDER DIFFERENCES OF CLINICAL MANIFESTATION AND CARDIAC REMODELING IN IDIOPATHIC HYPERTROPHIC CARDIOMYOPATHY IN ELDERLY PATIENTS

Aim. To study gender differences of clinical course and myocardial remodeling in elderly patients with idiopathic hypertrophic cardiomyopathy (HCM).Material and methods. The study included 131 patients with idiopathic HCM. Patients underwent standard clinical, laboratory and instrumental diagnostics.Results. In the elderly patients with idiopathic HCM, proportion of females was 63% (n=82), males — 37% (n=49). Mean age of females 69±7 y. o., males — 68±7 y. o. Coronary artery disease (CAD) was more common in males (32%) than in females (22%), but with no significant difference (p=0,2). Atrial fibrillation was more common in males (49% vs 29%, respectively, p=0,03). Size of the left atrium and enddiastolic size of the left ventricle in males exceeded those in females (51,2±9,0 mm versus 46,3±4,7 mm, 51,5±7,6 mm versus 45,6±5,7 mm, respectively, p=0,01). In males, symmetrical myocardial remodeling was found more often (42% vs 25%, p=0,04). Obstructive form of HCM was predominant in females (45% and 14%, p=0,01). Chronic heart failure (CHF) with NYHA class III was found in 29% in female group (n=24) and in 12% in male group (n=6), with a tendency to difference (p=0,06). In females, CHF with NYHA class III was mostly due to the left ventricle outflow tract obstruction (n=13) and dilatation phase (n=3). In males, almost all cases of CHF in NYHA class III-IV (8 of 9 patients) were a result of combination of HCM with CAD and previous myocardial infarction. In males, the ejection fraction was significantly lower (55,7±14,8% versus 62,2±10,9%, p=0,01).Conclusion. Proportion of females was higher in elderly patients with idiopathic HCM. Females with HCM were characterized by a more severe course of the disease due to the left ventricle outflow tract obstruction and dilatation phase. In males with idiopathic HCM there were registered more often the following: atrial fibrillation, larger left atrium and end-diastolic size of the left ventricle, symmetrical myocardial remodeling, lower ejection fraction of the left ventricle, — probably associated with a combination of HCM with CAD and previous myocardial infarction

ACROMEGALIC CARDIOMYOPATHY WITH DYNAMIC OBSTRUCTION OF THE LEFT VENTRICLE OUTFLOW TRACT

Aim. To explore genesis of the left ventricle hypertrophy in acromegaly patient, with the method of next generation sequencing.Material and methods. Standard clinical and laboratory minimum was done, with electrocardiography, 24 hour ECG monitoring, echocardiography, magnete resonance tomography of the heart, new generation sequencing on the IlluminaHiSeq 2000 equipment with simultaneous analysis of 108 genes associated with idiopathic hypertrophic cardiomyopathy (HCMP) and phenocopies of HCMP.Results. At the age 59 y. o. the female patient had beed first time diagnosed with asymmetric HCMP, non-obstructive type (interventricular septum 19 mm, posterior wall 11 mm, pressure gradient in outflow tract of the left ventricle (OTLV) — 25 mmHg). At the age 62 y. o. she developed HCMP with dynamic obstruction of OTLV (pressure gradient in OTLV up to 80 mmHg) with progressing dyspnea on exertion, and required non-surgical reduction of interventricular septum. By the computed tomography data, at the age 63 y. o. the patient was diagnosed with endocellar hypophysis microadenoma (a tumor 6,7*7,3 mm), somatotropic hormone — 53,39 mU/L (normal: 0,1-20 mU/L), insulin-like growth factor 1 — 359 ng/mL (normal: 118-314 ng/mL). However, with retrospective analysis of her photos, even from the age 40 y. o. there were enlarged hands, feet, nasal cartilages, ears, lips and eyebrow arcs that witness for long lasting disease course. With the new generation sequencing, there were no pathological mutations revealed.Conclusion. The case represents hypertrophic cardiomyopathy as a leading clinical sign in acromegalic cardiomyopathy that imitated idiopathic HCMP. Patient management in such case should include on-time etiopathogenetic therapy that works against disease progression, and in some cases even for regression of the left ventricle hypertrophy

NON-VAL30MET-TRANSTHYRETIN AMYLOID CARDIOMYOPATHY. LITERATURE REVIEW AND CLINICAL CASE

A literature review presented, with a clinical observation of non-Val30Mettransthyretin amyloid cardiomyopathy. Modern diagnostic and management algorithms discussed