Course Of Hypertrophic Cardiomyopathy Research Articles

Structural and Functional Impact of Adrenoceptor Beta-1 Gene Polymorphism in Patients with Hypertrophic Cardiomyopathy and Response to Beta-Blocker Therapy.

Hypertrophic cardiomyopathy (HCM) is a genetically inherited cardiac disorder with diverse clinical presentations. Adrenergic activity, primarily mediated through beta-adrenoceptors, plays a central role in the clinical course of HCM. Adrenergic stimulation increases cardiac contractility and heart rate through beta-1 adrenoceptor activation. Beta-blocker drugs are recommended as the primary treatment for symptomatic HCM patients to mitigate these effects. This prospective study aimed to investigate the impact of common ADRB-1 gene polymorphisms, specifically serine-glycine at position 49 and arginine-glycine at position 389, on the clinical and structural aspects of HCM. Additionally, the study explored the association between these genetic variations and the response to beta-blocker therapy in HCM patients. A cohort of 147 HCM patients was enrolled, and comprehensive assessments were performed. The findings revealed that the Ser49Gly polymorphism significantly influenced ventricular ectopic beats, with beta-blocker therapy effectively reducing them in Ser49 homozygous patients. Moreover, natriuretic peptide levels decreased, particularly in Ser49 homozygotes, indicating improved cardiac function. Left ventricular outflow obstruction, a hallmark of HCM, was also reduced following beta-blocker treatment in all patient groups. In contrast, the Arg389Gly polymorphism did not significantly impact baseline parameters or beta-blocker response. These results emphasize the role of the Ser49Gly polymorphism in the ADRB-1 gene in shaping the clinical course and response to beta-blocker therapy in HCM patients. This insight may enable a more personalized approach to managing HCM by considering genetic factors in treatment decisions. Further research with larger populations and longer follow-up periods is needed to confirm and expand upon these findings.

End-stage Hypertrophic Cardiomyopathy with Advanced Heart Failure in Patients Carrying MYH7 R453 Variants: A Case Series.

The MYH7 R453 variant has been identified in inherited hypertrophic cardiomyopathy (HCM) and is associated with sudden death and a poor prognosis. The detailed clinical course of HCM with the MYH7 R453 variant, from a preserved to a reduced left ventricular ejection fraction, has not been reported. We identified the MYH7 R453C and R453H variants in three patients who progressively developed advanced heart failure requiring circulatory support and summarized the clinical course and echocardiographic parameters of these patients over the years. Because of the rapid disease progression, we consider genetic screening for patients with HCM imperative for future prognosis stratification.

Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers.

Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiomyopathy. HCM is considered to be caused by mutations in cardiac sarcomeric protein genes. Recent research suggests that the genetic foundation of HCM is much more complex than originally postulated. The clinical presentations of HCM are very variable. Some mutation carriers remain asymptomatic, while others develop severe HCM, terminal heart failure, or sudden cardiac death. Heterogeneity regarding both genetic mutations and the clinical course of HCM hinders the establishment of universal genotype-phenotype correlations. However, some trends have been identified. The presence of a mutation in some genes encoding sarcomeric proteins is associated with earlier HCM onset, more severe left ventricular hypertrophy, and worse clinical outcomes. There is a diversity in the mechanisms implicated in the pathogenesis of HCM. They may be classified into groups, but they are interrelated. The lack of known supplementary elements that control the progression of HCM indicates that molecular mechanisms that exist between genotype and clinical presentations may be crucial. Secondary molecular changes in pathways implicated in HCM pathogenesis, post-translational protein modifications, and epigenetic factors affect HCM phenotypes. Cardiac loading conditions, exercise, hypertension, diet, alcohol consumption, microbial infection, obstructive sleep apnea, obesity, and environmental factors are non-molecular aspects that change the HCM phenotype. Many mechanisms are implicated in the course of HCM. They are mostly interconnected and contribute to some extent to final outcomes.

Features of Diagnostics and Course of Hypertrophic Cardiomyopathy in Real Clinical Practice

Introduction and purpose. Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular (LV) wall thickening not associated with increased afterload (hypertension and aortic stenosis), is usually caused by mutations in sarcomeric protein genes, and is inherited in an autosomal dominant manner. Unlike HCM, myocardial hypertrophy in its phenocopies is associated with the accumulation of substances such as amyloid, glycogen, etc. in the myocardium. The aim of our work was to analyze the features of the diagnosis and course of HCM in real clinical practice. Material and methods. A retrospective analysis of medical records of 80 patients (56.3 % of men) discharged with a diagnosis of HCM from a multidisciplinary hospital in Moscow in the period from 2007 to 2021 was carried out. The diagnosis of HCM in all patients was established on the basis of echocardiography data. The median age (25th and 75th percentiles are indicated in brackets) was 57 (48.5; 63) years. The duration of hospitalization was 8 (6; 12.5) days. Results. The reason for hospitalization was angina syndrome in 35 %, suspicion of acute coronary syndrome in 16.3 %, paroxysmal atrial fibrillation (AF) in 11.3 %, decompensation of chronic heart failure in 11.3 %, syncope in 7.5 % %, hypertensive crisis in 3.8 %, coronary angiography in 3.8 %, pacemaker implantation in 2.5 %, consultation with an arrhythmologist in 2.5 %, implantation of a cardioverter-defibrillator in 1.2 %, medical examination to resolve the issue of fitness for military service in 1.2 %, acute cerebrovascular accident in 1.2 %, hypotension in 1.2 %, drug bradycardia in 1.2 % of patients. Before hospitalization, a history of myocardial infarction was diagnosed in 15 %, arterial hypertension — in 53.8 %, chronic heart failure — in 77.6 %, chronic kidney disease — in 21.3 % of patients. Prior to the analyzed hospitalization, a history of myocardial infarction was diagnosed in 15 %, arterial hypertension in 53.8 %, chronic heart failure in 77.6 %, chronic kidney disease in 21.3 % of patients. LV wall thickness ≥1.5 cm was detected in 91.2 %, symmetrical form of hypertrophy — 22.1 %, apical — 5.2 %, papillary muscle hypertrophy — 1.3 %, interventricular septum — 71.4 % of patients. Permanent obstruction of the LV outflow tract (LVOTO) was detected in 62.8 % (9.0 % of patients had a history of septal reduction), transient LVOTO — in 1.3 %, non-obstructive HCM — in 35.9 %. The ejection fraction (EF) of the LV (according to Simpson) was 63 (55-70) %, CHF with reduced LV EF <40 % was detected in 3.8 %, with a moderately reduced LV EF (40-49 %) — in 5 %, with preserved LV EF — in 68.8 % of patients. Anterior systolic movement of the anterior leaflet of the mitral valve occurred in 47.5 %, prolapse of the anterior leaflet of the mitral valve was described in 7.14 %. Mitral regurgitation was registered in 75 % of patients. 45 % of patients with HCM suffered from AF: permanent 15 %, paroxysmal 23.8 %, persistent 6.2 % of patients. During hospitalization, ventricular tachycardia was registered in 7.5 %, supraventricular tachycardia — 3.8 %, conduction disturbances were noted in 36.3 % of patients, of which atrioventricular block in 6.3 %, blockade of the right bundle branch block in 21.3 %, left bundle branch block in 15 %, and Wolff-Parkinson-White syndrome in 1.3 % . Implantation of a pacemaker in history was in 5 %, including in connection with MorgagniAdams-Stokes attacks — in 3.8 % of patients. During a median follow-up of 87 (interquartile range 45–131.5) months, 13.8 % of patients with HCM died. In deceased patients, LVOTO was significantly more common (in the dead 100 %, in the living 58.2 %, p = 0.006) and AF (in the dead 72.7 %, in the living 40.6 %, p = 0.047). Genetic testing and exclusion of HCM phenocopies was not performed during hospitalization and was not recommended for any patient. Conclusion. In real clinical practice, in most cases, only phenotypic diagnosis of HCM is carried out according to echocardiography, and screening for genetic mutations and HCM phenocopies is not performed. It is necessary to widely introduce genetic testing and screening for HCM phenocopies for the timely diagnosis of pathology that requires the appointment of specific pathogenetic therapy to improve the prognosis of patients

Lifetime Clinical Course of Hypertrophic Cardiomyopathy: Outcome of the Historical Florence Cohort Over 5 Decades

BackgroundThe current understanding of the clinical course and long-term outcome of patients with hypertrophic cardiomyopathy (HCM) has been extrapolated from cohorts with relatively short follow-up, usually <10 years. Extended assessments more closely reflecting HCM lifetime burden are not available. ObjectivesThe purpose of this study was to report the lifetime clinical course of HCM. MethodsWe analyzed the clinical course of HCM patients diagnosed at our center from 1970 to 1992 and followed annually to the present. Cumulative incidence functions were used to estimate the incidence of HCM-related mortality (including heart failure [HF]/stroke related, sudden cardiac death [SCD]) and non-HCM related. ResultsA total of 202 patients (age 41 ± 17 years; 63% male) were followed 27 ± 6 [range: 3-50] years. Overall, 97 (48%) survived and 105 (52%) died during the particularly long follow-up; 69 deaths were related to HCM, including 53 HF related, 11 fatal embolic strokes, and 16 SCDs. Annual overall HCM-related mortality was 1.3%/y, increasing from 0.7% during the first decade to 1.8% in the second/third decade (P < 0.01), mainly driven by increase in HF-/stroke-related events (from 0.6% to 1.3%). The SCD mortality rate was similar in the 2 periods (0.1% vs 0.44%, P = 0.10). Of the 69 HCM deaths, 29 (42%) occurred before the widespread availability of effective contemporary treatment strategies and are considered potentially preventable. ConclusionsIn this unique HCM cohort followed for up to 50 years, often before contemporary therapies became widely implemented for HCM, HF frequently progressed over time, while arrhythmic SCD events were less common and remained constant over time. Despite spanning different management eras over 5 decades, HCM-related mortality remained relatively low (1.3%/y).

First results of maintenance of register in electronic form in pediatric patients with hypertrophic cardiomyopathy

Background. The problem of managing children with hypertrophic cardiomyopathy (HCM) remains relevant due to the high risk of sudden cardiac death (SCD). Registers of patients with HCM contribute to a better understanding of the course of the disease and its outcomes.Objective. To study the structure of CMP with a hypertrophic phenotype, as well as to identify clinical, molecular and genetic features of the course of HCM and outcome in children based on anamnestic, clinical and instrumental data from an electronic database.Design and method/ Currently, the database includes complete information on 80 children from 0 to 18 years of age inclusive with a hypertrophic phenotype of CMP. The study was performed on the basis of the Department of Pediatric Cardiology and Medical Rehabilitation of the V.A. Almazov” of the Ministry of Health of Russia. The database contains the history of the disease and family history, the results of clinical and laboratory-instrumental examination, the results of molecular genetic research. The register is dynamically updated.Results. The mean age of onset of HCM was 1.75 [0.02; 10.00] years. There were more boys than girls — 54 (67.5 %). The main complaints were decreased exercise tolerance in 35 (43.8 %) children and shortness of breath in 30 (37.5%) children. All children had signs of heart failure (HF): 53 (66.3 %) had signs of functional class 2 HF, 26 (32.5 %) — functional class 1 and 1 (1.2 %) — functional class 3. Ventricular arrhythmias were recorded in 23 (29 %) children, unstable ventricular tachycardia in 2 (2.5 %) children. Myocardial fibrosis of the left ventricle according to the results of MRI of the heart was found in 60.7 %. A lethal outcome was registered in 5 % (n = 4) of cases on average at 241 ± 117 days of life. All the deceased had phenocopies of HCM.Conclusion. Maintaining an electronic database of patients with HCM will allow a better understanding of the influence of factors, including genetic ones, on the course, outcomes, and prognosis of the disease in the pediatric population.

Clinical course of patients with hypertrophic cardiomyopathy away from tertiary referral care.

Data on the clinical course of hypertrophic cardiomyopathy (HCM) are mainly derived from tertiary HCM centre studies, and knowledge of clinical outcomes of patients leaving specialty care and returning to local physicians is limited due to gaps between clinical encounters or complete loss of follow-up. This survey aims to describe the clinical course of HCM in patients following their evaluation at a tertiary referral centre. A comprehensive outcomes survey was developed and sent to 4495 eligible patients with HCM previously evaluated at Mayo Clinic. Questions assessed general well-being, New York Heart Association class, procedures performed, and probable HCM-triggered ventricular arrhythmic events (VAEs) since last visit. In total, 2058 patients (mean age 63±15years; 42% female) responded to the survey covering a total of 10510 patient-years with an average of 5.4±6.4years of follow-up since their last on-campus/virtual visit to Mayo Clinic. During their time away from specialty care, 20% of patients reported having cardiac-related hospitalizations and 25% reported having cardiac-related procedures. Similar to high-risk referral cohorts, 5% of patients reported VAEs with an event rate of 0.98 events/100 patient-years. The prevalence of atrial fibrillation, syncope, pre-syncope, cardiac-related hospitalizations, and VAEs during time away from specialty care increased significantly with increasing New York Heart Association class (P<0.001). Acknowledging ascertainment bias, the clinical course of patients away from tertiary care may be more severe than previously anticipated. Among those with exertional symptoms, HCM-related morbidity increased substantially. Higher risk HCM patients should remain in contact with HCM specialty care.

Clinical features of hypertrophic cardiomyopathy depending on the hereditary factor

The objective was to study the clinical features of symptomatic hypertrophic cardiomyopathy (HCM) depending on the form (familial / non-familial), the age of onset and the presence of arterial hypertension (AH).Methods and materials. During 6 years, we examined 250 HCM patients, 100 patients with symptomatic HCM aged from 18 to 86 years were included in the study. Results. Patients with the clinical manifestations onset at a young age more often had a familial form of the disease, an autosomal dominant type of inheritance, an asymmetric HCM with reverse curve interventricular septal morphology. On the contrary, patients with the clinical manifestations onset at the age of ≥45 years had non-familial form of the disease and asymmetric HCM with basal interventricular septal hypertrophy. The young HCM patients with associated AH more often were obese, had CHF of III–IV functional class (NYHA), larger anteroposterior left atrial diameter than patients without AH and more often needed interventricular septal reduction. HCM patients and associated AH with the disease onset at the age of ≥45 years significantly more often had angina syndrome. Absolute indications for interventricular septal reduction in HCM patients with the disease onset ≥45 years of age were determined only for HCM patients and associated AH. At the same time, 50 % of HCM+AH patients both at a young age and in the older group, had obesity. Conclusions. The interventricular septal morphology differs significantly depending on the age of clinical manifestations onset. Co-existing AH and obesity are predictors of the progressive HCM course and an increase in the proportion of patients with absolute indications for interventricular septal reductions regardless of the age of clinical manifestations onset.

The impact of adrenoceptor-1 gene polymorphism on structural and functional features in patients with hypertrophic cardiomyopathy

Abstract Background The adrenergic system plays a central role during the clinical course of hypertrophic cardiomyopathy (HCM) and hence beta-blocker therapy is the first-line treatment option according to current guidelines. Previous studies demonstrated variable cellular response to an adrenergic stimulus due to adrenoceptor-1 (ADRB-1) gene polymorphism in several patient groups including hypertension and dilated cardiomyopathy. Moreover, the impact of beta-blockers is also variable in these patients. Purpose We aimed to investigate the impact of ADRB-1 gene polymorphism on structural and functional features among patients with HCM. Methods In this study, we investigated the roles of Arginin389Glycine and Glycine49Serine polymorphism. Patients with a clear diagnosis of HCM according to current guidelines were included. Structural features including maximal wall thickness, interstitial fibrosis and left ventricular/atrial volumes were obtained using cardiac MRI and transthoracic echocardiography. Functional features including heart rate, blood pressure, left ventricular outflow obstruction were also recorded. The risk of sudden cardiac death was calculated using the HCM risk score. The impact of beta-blocker therapy on heart rate and blood pressure were also compared. Results After the exclusion of patients, 147 patients were included in the study. 77% of the study population were male and the mean age was 49.5 years. The hypertrophic segment was septum in 83% of the study population. The mean maximum wall thickness was 20 mm (19–23). With respect to Ser49Gly polymorphism, Serine homozygotes demonstrated higher late-gadolinium enhancement and indicator of interstitial fibrosis (p: 0.007). In concordance with higher LGE, the presence of fragmented QRS on surface ECG (p: 0.026) and a higher prevalence of non-sustained ventricular tachycardia (p: 0.016) in these patients were observed. The risk of sudden cardiac death was also higher in Ser49 homozygotes (p: 0.041). However, with respect to Arg389Gly gene polymorphism, there was no significant difference between Arg389 homozygotes, Arg389Gly heterozygotes and Gly389 homozygotes in terms of structural and functional features. The vast majority of patients reported improved functional capacity and decreased shortness of breath during the follow-up regardless of ADRB-1 gene polymorphism which is objectively validated by decreased pro-BNP levels in all patients. Conclusion Our results indicated that ADRB-1 gene polymorphism, particularly Ser49Gly gene polymorphism may have a significant role during the clinical course of HCM. Since Ser49 homozygote patients demonstrated higher interstitial fibrosis and a higher risk of sudden cardiac death, further studies are required to determine the significance of Ser49Gly gene polymorphism in HCM patients. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Bilimsel Arastırma Projesi (BAP) - Istanbul University - Cerrahpasa, Cerrahpasa Medical School

Novel molecular insights and potential approaches for targeting hypertrophic cardiomyopathy: Focus on coronary modulators

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder that associates with nucleotide sequence variants in genes encoding sarcomere related proteins, and is recognized as the most common heritable cardiac diseases. Clinically, HCM can be extremely variable and this makes the diagnosis difficult until the development of serious or fatal events. Nevertheless, the main hallmark of HCM is represented by left ventricle hypertrophy that can be occasionally associated to cardiac arrhythmias, chest pain, diastolic dysfunction, obstruction of left ventricular outflow tract. The present review aims to focus on the complex interplay existing between the multifaceted non-genetic molecular mechanisms underlying HCM onset and progression, and the key pathophysiological role of abnormal coronary artery function. As the clinical course of HCM shows a mortality rate per year up to 6% the importance of innovative therapeutic strategies will be discussed, especially in regard to the use of potential endogenous coronary modulators to be enrolled as modifiers of HCM phenotype.

PO-704-01 CLINICAL COURSE OF PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY AWAY FROM TERTIARY REFERRAL CARE

Hypertrophic cardiomyopathy (HCM) is one of the most common genetic heart diseases characterized by asymmetric left ventricular hypertrophy (LVH). Advances in diagnosis and management have made HCM a manageable disease with reduced morbidity and mortality. The clinical course of HCM mainly derives from studies in tertiary HCM centers. However, these studies are limited due to gaps in follow-up between clinical encounters or loss of follow-up as local physicians resume care.

Correlation between markers of fibrosis and myocardial remodeling in patients with various course of hypertrophic cardiomyopathy

Aim. To assess the relationship between fibrosis markers and structural and functional parameters in patients with various types of hypertrophic cardiomyopathy (HCM).Material and methods. This prospective comparative non-randomized study included 49 patients with HCM. Patients were divided into 3 groups according to the disease course: group 1 — stable course (n=12; men, 8 (67%), mean age ‒ 41±12 years); group 2 — progressive course (n=26; men, men, 16 (61%). mean age — 57±11 years); group 3 — patients with atrial fibrillation (AF) (n=11; men, 4 (36%), mean age — 63±6 years). Patients underwent standard clinical and paraclinical investigations. The levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) were determined in all patients using enzyme-linked immunosorbent assay in blood serum.Results. In all patients with HCM, elevated levels of MMP-9 and TIMP-1 are noted compared to the reference values. In group 1, the MMP-9 level [Me (Q1; Q3)] was 226 (201;271) ng/ml; TIMP-1 — 410 (267;488) ng/ml; in group 2, the MMP-9 level was 236 (187;285) ng/ml; TIMP-1 — 421 (321;499) ng/ml. In the course with AF, the MMP-9 level was 260 (228;296) ng/ml, while TIMP-1 — 381,5 (305;466) ng/ml; no significant difference was revealed (p=0,59; p=0,90, respectively). A correlation was found between age and MMP-9 levels, as well as between MMP-9 levels and left atrial volume (p=0,034; p=0,035, respectively).Conclusion. The high activity of matrix metalloproteinases and their tissue inhibitors reflects enhanced fibrosis and myocardial remodeling in HCM, which is especially characteristic of patients with AF.

Transcatheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy: Long-term results and clinical outcomes.

Radiofrequency transcatheter ablation (RFCA) for atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM) has been proven feasible. However, the long-term results of RFCA and its impact on clinical course of HCM are unknown. The aim of this study was to analyse clinical outcomes and long-term efficacy of RFCA in a multicentre cohort of patients with HCM and concomitant AF. Patients with HCM and AF consecutively undergoing RFCA were included. Ablation failure was defined as recurrence of AF, atrial tachycardia, or flutter lasting more than 3 min and occurring after the blanking period. Overall, 116 patients with symptomatic AF refractory to antiarrhythmic drugs were included. Over a median follow-up of 6.0 years (interquartile range: 3.0-8.9 years) recurrence rate after a single RFCA was 32.3 per 100 patient/years with 26% of patients free from AF relapses at 6-year follow-up. Among patients experiencing AF recurrence, 51 (66%) underwent at least one redo-procedure. The overall recurrence rate considering redo-procedures was 12.6 per 100 patients/years with 53% of patients free from AF relapses at 6 years. At last follow-up, with an average of 1.6 procedures, 67 (61%) patients were in sinus rhythm (SR). Patients remaining in SR showed better functional status compared with those experiencing arrhythmic recurrences (NYHA Class 1.6 ± 0.1 vs. 2.0 ± 0.1, p = .009). RFCA of AF in HCM patients is an effective and safe strategy favoring long-term SR maintenance, reduction of atrial arrhythmic events, and improved functional status. However, most patients need repeat procedures and continuation of antiarrhythmic drugs.

Abstract 14705: Clinical Profile and Health Disparities in Patients With Hypertrophic Cardiomyopathy in a Multi-ethnic Cohort

Background: The clinical characteristics and management of hypertrophic cardiomyopathy (HCM) are well-described in European cohorts. However, less is known about other ethnic groups. We compared demographic, clinical, genetic and service use characteristics of patients with HCM across major ethnic groups represented in our cohort. Methods: Retrospective cohort study of 812 HCM probands attending a specialised clinic between 2002 and 2020. The ethnic groups were European n=611, East Asian n=75, South Asian n=58 and Middle Eastern and North African n=68. Analysis included one-way ANOVA with Dunnett's post-hoc comparison or Bonferroni adjustment. Results: The mean age was 55 ± 17 years and 527 (65%) were male. Using the European group as the control, East Asians had a lower body mass index (29 versus 25 kg/m 2 , p&lt;0.05) and South Asians had a lower prevalence of atrial fibrillation (10% versus 31%, p&lt;0.02). Differences also existed in echocardiographic characteristics with East Asians more likely to have apical hypertrophy (23% versus 6%, p&lt;0.02 and Middle Eastern and North African patients more likely to present with left ventricular outflow tract obstruction (46% versus 34%, p&lt;0.02). East Asians were less likely to undergo genetic testing (55% versus 85%, p&lt;0.02) or have an implantable cardioverter defibrillator (19% versus 36%, p&lt;0.02) despite similar HCM-Risk score. Middle Eastern and North Africans and South Asians had the highest rates of variants of unknown significance (27% and 21%, p&lt;0.02; Fig A), while East Asians were more likely to have a causative sarcomere gene variant other than MYBPC3 or MYH7 (58% versus 11%, p&lt;0.02 (Fig B). Conclusion: We demonstrate variability in the phenotype expression and management of HCM by ethnic group, representing differences in pathophysiology, sociocultural contexts, and access to healthcare. This may indicate a role of ethnicity in understanding the clinical course of HCM, and highlight disparities faced by some groups.

Characterisation of circulating microRNA-21 levels in patients with hypertrophic cardiomyopathy

To study the levels of circulating microRNA-21 in patients with hypertrophic cardiomyopathy (HCM) of different ages. The study included 49 patients with HCM. The proportion of females was 55.1%, males 44.9%. The average age was 50 [32; 65] (from 19 to 86 years). The control group for microRNA-21 included 44 healthy individuals, respectively, matched by the age and sex with the studied patients. Patients was made in accordance with the recommendations of the European society of cardiology. Plasma microRNA expression was determined by PCR with reverse transcription and real-time detection of results. The relative level of gene expression was calculated in accordance with the standard procedure 2-Ct. Septal wall thickness at end diastole has a significant negative correlation with age in patients with HCM (r=-0.56; р0.001). PWTd (posterior wall thickness at end diastole) has a significant positive correlation with age in patients with HCM (r=0.67, р0.001). The level of circulating microRNA-21 in plasma is higher in patients with HCM compared to healthy individuals (5.28 [2.64; 13.96] and 0.84 [0.55; 1.23], respectively; p0.001). Significantly higher levels of microRNA-21 were found in young patients aged from 19 to 45 years with the symptomatic course of HCM (36.76 [5.66; 42.22]) compared to patients with asymptomatic course 45 years of age (2.81 [1.45; 5.28]; p0.002) and symptomatic patients 45 years (3.88 [2.16; 8.63]; p0.002).) The calculated risk of SCD was significantly higher in young symptomatic patients with HCM (6.01 [3.64; 9.67]) compared to patients with asymptomatic course 45 years (2.41 [1.21; 3.89]; p0.001) and symptomatic patients 45 years (2.56 [1.67; 4.41]; p0.001). The level of circulating microRNA-21 is significantly in patients with HCM compared to control group. The maximum level of circulating microRNA-21 was detected in patients with symptomatic course of HCM at the age of 45 years.

Gender-specific differences in clinical profile of hypertrophic cardiomyopathy and their association with the polymorphic variant rs1739843 of the hspb7 gene

Objective. The aim of this study was to investigate gender-specific differences in the clinical profile of hypertrophic cardiomyopathy (HCM) and to determine the impact of polymorphic variant rs1739843 of the HSPB7 gene on clinical profile and outcomes in women and men with HCM. Design and methods . The study population consisted of 171 patients with HCM ≥ 18 years old. A novel disease pathway model was employed to assess clinical course of HCM. Single nucleotide polymorphism (SNP) rs1739843 of the HSPB7 gene was genotyped by allele-specific real-time polymerase chain reaction assay. Results. We found no significant gender-specific differences in clinical course of HCM in patients ≥ 18 years old during 10-year follow-up. High prevalence of T allele of rs1739843 of the HSPB7 gene was observed in women > 18 years old with HCM and chronic heart failure (CHF) with preserved ejection fraction (EF) ( ≥ 50 %) (C: Т , odds ratio (OR) = 0,213, 95 % confidence interval (CI) = 0,077-0,593, p 18 years old.

113 Echocardiographic assessment of right ventricular outflow tract obstruction in hypertrophic cardiomyopathy - efficacy of dual chamber pacing in reducing of gradient

Abstract Hypertrophy of the right ventricle (RV) in the course of hypertrophic cardiomyopathy (HCM) is found in 30-60% of cases, with the possibility of a right ventricular outflow tract obstruction (RVOTO), obstruction in the apex or the middle part of the right ventricle. A patient, aged 41, admitted due to limitation of exercise tolerance, effort dyspnea, presyncope. In an echocardiogram, interventricular septum (IVS) hypertrophy was observed up to 2.0 cm; normal size of the heart cavities; normal left ventricular systolic function (EF-70%). A color doppler mapping detected the zone of flow acceleraction and turbulent flow in right ventricular outflow tract (RVOT), next a spectral doppler examination showed the RVOT obstruction with a maximal gradient of 64 mmHg. Because of the suboptimal echocardiographic imaging, a heart CT scan was performed, revealing the features of left ventricular hypertrophy, most severe at the base and the medium part of IVS (up to 25 mm). Asymmetric hypertrophy of the middle portion of the right ventricle and right ventricular outflow tract obstruction was also observed. A hemodynamic study confirmed the presence of gradient in RVOT, up to 40 mmHg. Holter electrocardiogram recorded an episode of non-sustained ventricular tachycardia. Taking into account the clinical picture, the family history of the disease, and calculated HCM Risk SCD (7.55%), the decision was made to implant a dual chamber cardioverter defibrillator. The defibrillator electrode was fixed at the apex of the right ventricle. A short AV delay was programmed for prevalent right ventricular stimulation (AV delay 100 ms), resulting in 99.6% ventricular stimulation. The control echocardiogram showed a reduction in the maximum gradient in RVOT to 24 mmHg. In addition, the patient was treated with a beta-blocker. To sum up, in the case of HCM we should always examine the RV with color and spectral doppler to exclude potential narrowing in RV. Constant AV sequential stimulation with a short AV delay is a recognized method that can be considered in symptomatic adult HCM patients with a left ventricular outflow tract obstruction. In the case described here, the above mentioned method proved effective in the significant reduction of the gradient in the right ventricular outflow tract. Abstract 113 Figure. gradient in RVOT

Трудности диагностики и варианты клинического течения гипертрофической кардиомиопатии у больных пожилого возраста

Hypertrophic cardiomyopathy (HCM) is a genetically determined disease with a morphological abnormality of myocardial contractile proteins, manifested by asymmetric left ventricular myocardial hypertrophy. Currently, there is evidence that the HCM incidence rate in the population can be up to 1:200, as opposed to the traditionally quoted 1:500. In early works on HCM, this disease has been mostly perceived as a pathology of young and middle age with a high risk of sudden cardiac death. Now it is generally accepted that patients with HCM are likely to reach the old or even geriatric age subject to the benign course of the disease. Comorbidity in such patients contributes to the clinical aspect of the disease. The article deals with problem areas of HCM diagnostics in elderly patients with an emphasis on differential diagnosis of HCM and left ventricular hypertrophy as part of hypertension. It contains a discussion of differential diagnosis of ischemic heart disease in HCM. The authors also focus on the specifics of the course of HCM in old age patients and present factors affecting the prognosis for this group of patients.

Polymorphic variant rs1739843 of heat shock protein beta-7 (HSPB7) gene and its relationship with on clinical profile and outcomes in patients with hypertrophic cardiomyopathy (results of a 10-year follow-up)

Aim. To determine the impact of polymorphic variant rs1739843 of the HSPB7 gene on clinical profile and outcomes in patients with hypertrophic cardiomyopathy (HCM).Material and methods. The study population consisted of 108 patients with HCM ≥45 years old. The control group included 192 healthy donors. The design of the study included an assessment of the clinical course, determining the outcome of HCM using a new methodological approach proposed by Rowin EJ, et al. (2017). Polymorphic variant rs1739843 of the HSPB7 gene was genotyped by allele-specific real-time polymerase chain reaction (PCR) assay.Results. It was found a significant increase in frequency of TT genotype of rs1739843 of the HSPB7 gene in patients with HCM — 20,4%, compared with control group — 4,2% (ТТ: ТС+СС, odds ratio (OR) =5,88, 95% confidence interval (CI) =2,52-13,75, p&lt;0,001). High prevalence of CC genotype of rs1739843 of the HSPB7 gene was observed in control group — 80,2% vs 31,5% in HCM group (CC: ТС+TT, OR=0,11, 95% CI=0,07-0,19, p&lt;0,001). The allele frequency (С:Т) also differs between HCM and control groups — 55,6:44,4% in HCM vs 88,02:11,98% in control group (OR=5,88, 95% CI=3,91-8,85, p&lt;0,001). It was also found a significant increase in frequency of TT genotype and T allele of rs1739843 of the HSPB7 gene in HCM patients with oligosymptomatic HCM course — 16,7%, compared with control group — 4,2% (ТТ: ТС+СС, OR=4,60, 95% CI=1,63-12,99, p&lt;0,001). HCM patients ≥45 years old showed a significant increase in T allele frequency in cases of presence of 2 (FC III-IV CHF (chronic heart failure)+AF (atrial fibrillation), 18,8% vs 6,6%) and 3 adverse pathways (FC III-IV CHF+AF+SCD (sudden cardiac death), 4,2% vs 1,6%).Conclusion. HCM progression along 2 and more adverse pathways in patients ≥45 years old has been characterized with adverse outcome. The T allele and TT genotype of rs1739843 of the HSPB7 gene were more frequent in patients with HCM ≥45 years old, compared with control group. It was also found a significant increase in frequency of TT genotype and T allele of rs1739843 of the HSPB7 gene in HCM patients with oligosymptomatic HCM course, compared with control group.Allele T of rs1739843 of the HSPB7 gene is associated with 2 and more adverse pathways of HCM progression.

P1610The genetic background of the disease in a group of patients with severe course of hypertrophic cardiomyopathy

Abstract Background End-stage hypertrophic cardiomyopathy (esHCM) indicates the most progressive form of HCM with progression to left ventricle remodeling and systolic dysfunction and is common indication to heart transplant. It affects 2.4–15.7% of HCM cases and is associated with a poor prognosis (mortality in this group of patients reaches 11%). Purpose In this study patients with esHCM were investigated using next generation sequencing in order to examine the genetic causes of the most severe course of the disease. Despite huge amount of data from many studies, a clear genotype-phenotype correlation is still lacking and predictive value of genetic testing is sometimes undermined. However, there is an ongoing need for a prediction factors in HCM patients. Methods Fifty seven patients (21 male, 36.8%) with esHCM were genetically investigated with next generation sequencing of a TruSight Cardio panel by Illumina that provides coverage of 174 genes with known associations to cardiac conditions including cardiomyopathies (n=52) or custom panel of 35 cardiomyopathies genes (n=5). Results Disease-causing variants where found in 47 probands (82.5%). Thirty-two probands (77.2%) had a single pathogenic or potentially pathogenic mutation in one of the sarcomeric genes: MYBPC3 (13, 22.8%), MYH7 (11, 19.3%), TNNT2 (3, 5.3%), TNNI3 (3, 5.3%), MYL3 (1, 1.8), TPM1 (1, 1.8%). In 13 (22.8%) probands we found a double mutation: in 7 (12.3) both variants sarcomeric (MYBPC3 and TNNT2 with MYH7, MYBPC3 and ACTA1) and in 5 (8.8%) one sarcomeric and the second non-sarcomeric cardiomyopathy variant (BAG3, ILK, PRKAG2, RBM20, SCN5A). In 3 (5.3%) probands we identified mutations or potentially disease-causing variants in genes associated Danon disease (LAMP2), glycogen storage disease of heart (PRKAG2) and double mutation FHL1 + PTPN11 (myopathy/Emery-Dreifuss muscular dystrophy and Noonan syndrome). In 10 (17.5%) patients, genetic examination did not reveal a candidate for disease-causing mutation. Surprisingly, a half of them had documented familial history of the disease. The majority of mutations in MYBPC3 were truncating variants (14/18, 78%). Thirty-three probands (57.9%) had a heart transplant or qualification to the procedure. Conclusion Despite a similar background of typical HCM and esHCM and still ambiguous genotype-phenotype correlation, results may indicate that certain mutations (and not genes) may determine a more severe course of the disease. The majority of truncating variants in MYBPC3 gene may suggest their very strong impact on the course of the disease. Also, 3 neighboring variants in TNNT2 gene indicate a hot spot region for esHCM in our population. As expected, in single cases esHCM was related to specific non-sarcomeric genes (LAMP2, PRKAG2, FHL1). 17.5% of unsolved cases suggests that in such cases whole exome/genome sequencing might be needed to recognize the disease-causing mutation, especially when disease is familial. Acknowledgement/Funding This work was supported by a grant 2.7/II/17 from the Institute of Cardiology, Warsaw, Poland.