Морфологическое исследование телоцитов в левом предсердии у пациентов с длительно персистирующей фибрилляцией предсердий

Objective To evaluate prospects for clinical use of circulating biomarkers for characterizing fibrotic changes in the myocardium of patients with hypertrophic cardiomyopathy (HCMP) with left ventricular (LV) outflow tract obstruction. Materials and Methods This was a prospective study with a 12-month follow-up period. The study included 47 patients (29 females and 18 males) with obstructive HCMP who were selected for septal reduction. Echocardiography (EchoCG), cardiac magnetic resonance imaging (MRI) and measurements of serum C-reactive protein, N-terminal pro-brain natriuretic peptide, and relevant circulating markers of fibrosis (TGF-β1, MMP-2,-9, TIMP-1, galectin-3, sST2, CITP, PICP, and PIIINP) were performed for all patients. All patients were evaluated at baseline and at 7 days, 6 and 12 months following surgical treatment. Morphometrical analysis of intraoperative biopsy samples was performed for evaluation of the degree of fibrotic changes. Patients received beta-blockers (95.7%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (34%), loop diuretics (68.1%), aldosterone antagonists (34%), and statins (66%). Results Women with HCMP were older and more frequently had additional risk factors (arterial hypertension). Men had a higher risk of sudden cardiac death. Histological study of intraoperative myocardial biopsy samples showed that the area of fibrotic changes was 13.9±6.9%. According to cardiac MRI mean area of delayed contrast enhancement was 8.7±3.3% of LV myocardial mass. No association was established between traditional cardiovascular risk factors and severity of myocardial fibrotic changes or levels of circulating fibrosis markers. Perhaps that was due to the modifying effect of the drug therapy received by HCMP patients. According to EchoCG maximum pressure gradient in the LV outflow tract before the surgical treatment was 88 (55; 192) mm Hg, and interventricular septal thickness was 22 (16; 32) mm. A considerable decrease (p=0.0002) in the LV outflow tract gradient was observed after myectomy in all patients. At the same time, the left ventricular dimension, which tended to decrease in the early postoperative period, returned to baseline values by the 6th month of follow-up. Conclusion The study confirmed the increase in relevant circulating markers of fibrosis in patients with obstructive HCMP. At the same time, no correlation was observed between levels of circulating biomarkers and severity of fibrosis according to data of histology and cardiac MRI, which was probably due to the modifying effect of drug therapy and limited sampling.

Aim. To analyze 20 electrocardiographic (ECG) signs of left bundle branch block (LBBB) before and after septal myectomy in patients with hypertrophic cardio myopathy (HCM) and develop a criterion for proximal LBBB based on the selected signs.Material and methods. This retrospective non-randomized study included 50 patients with obstructive HCM who underwent septal myectomy. There were following inclusion criteria: QRS width <120 ms before surgery, transaortic access during septal myectomy, and QRS width ≥120 ms in the early postoperative period. For each patient, ECGs were analyzed before septal myectomy and in the first week after surgery. At the same time, 20 ECG signs proposed earlier in the LBBB criteria were independently assessed.Results. Exsection of a small myocardial area of the basal interventricular septal parts, weighing an average of 4,9±2 grams, led to a significant increase in the QRS width (by 61±14,6 ms) and the prevalence of almost all ECG signs of LBBB. In 100% of cases (n=50), the following signs demonstrated significant dynamics after surgery: (1) midQRS notching or slurring in ≥2 contiguous leads (I, aVL, V1-V2, V5-V6); (2) absence of q wave in V5-V6 and (3) discordant T wave in at least two leads (I, aVL, V5, V6). Based on the design of the study, (4) QRS width ≥120 ms was additionally included. These ECG characteristics were combined into a new criterion for proximal LBBBConclusion. A new criterion for proximal LBBB was developed using the pathophysiological model of iatrogenic conduction block of left bundle branch. Further estimation of this criterion on a set of candidates for CRT with heterogeneous level of LBBB is necessary.

Anderson–Fabry disease (AFD) results from decreased enzyme activity of lysosomal enzymes and intralysosomal storage of nonhydrolyzed forms. Cardiovascular complications, mainly in the form of HCM, contribute substantially to AFD patient mortality. Here, we report three new cases of obstructive HCM (HOCM) in nonclassical presentations of AFD and isolated cardiac involvement. In all three cases, the diagnosis of AFD was made postoperatively by routine genetic and morphological testing. Together with previously published cases, this report illustrates the potential safety and beneficial effect of septal surgical myectomy in patients with AFD-HOCM, as well as underlines the need for more thorough screening for clinical signs of AFD-associated cardiomyopathy and GLA variants among patients with HOCM.

Background: At present, there are no methods for intraoperative monitoring of the interventricular septum (IVS) thickness in a stopped and empty heart. This might be an obvious reason for unsatisfactory results after a number of septal myectomies.Aim: To provide an experimental background for the method to control the IVS thickness (that we had proposed) during septal myectomy.Materials and methods: The proposed technique is based on the transillumination method. The experimental models were cadaveric porcine hearts, as well as fragments of the human myocardium removed during septal myectomies. The thickness of the translucent myocardium was estimated depending on the local illumination value at the entrance to the myocardium and the external illumination of the surgical field. We compared the results of 67 septal myectomies performed in the clinic of the Almazov National Medical Research Centre with the results of 35 similar experimental procedures with cadaveric porcine hearts using the proposed way of measurement.Results: A graph of the illumination at the entrance to the myocardium against the thickness of the translucent myocardium was constructed. After conventionally performed septal myectomies the median variation of the myocardial thickness was 4 [3; 6] mm. In the experiment using the proposed control method, the median variation was 1 [1; 2] mm, i.e. significantly less than with the conventional approach (p = 3 x 10-10).Conclusion: The method to control the IVS thickness when performing septal myectomy makes it possible to achieve the required myocardial thickness the resection area with much greater accuracy than with the conventional one.

Aim. To determine the prevalence and profile of rare variants of the filamin C gene (FLNC) among patients with hypertrophic obstructive cardiomyopathy (HCM) referred for septal myectomy, and to provide a clinical description of HCM occurring with these variants.Material and methods. Ninety-eight adult patients with HCM who underwent septal myectomy underwent genetic testing by next-generation sequencing using a targeted cardiac panel (39-gene panel in 58 patients and 17-gene panel in 40 patients). In patients with rare FLNC variants (with a minor allele frequency <0,01%), the data of anamnesis, echocardiography, electrocardiography, Holter monitoring, and myocardial histological examination were analyzed.Results. Four patients with rare FLNC variants (two men and two women) were identified, which amounted to 4% (Pro1774Ser, Thr1317Pro and His1834Tyr, the latter was detected twice). These variants were missenses and classified as variants of uncertain clinical significance. The FLNC p.Thr1317Pro variant in one patient was combined with a pathogenic variant p.Val606Leu in MYH7 gene. All patients received diagnosis of HCM after age of 40 years. Clinical course was represented by mild symptoms of heart failure and class II stable angina. Episodes of non-sustained ventricular tachycardia, atrial fibrillation or clinically significant conduction block were not registered. One patient with p.His1834Tyr FLNC variant had reverse curve interventricular septum morphology, whereas other patients had predominant hypertrophy of basal segment of interventricular septum. Diastolic dysfunction did not exceed grade 1-2 in all four patients.Conclusion. The clinical characteristics of carriers of rare FLNC variants in our study did not differ from the majority of patients with HCM who underwent septal myectomy. Rare FLNC variants can act as causative or modifying factors of HCM course. Functional and population-based studies using segregation analysis should clarify the pathogenicity of rare FLNC variants.