Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease with an estimated prevalence of up to 1 in 200 individuals. In the majority of cases, HCM is considered a Mendelian disease, with mainly autosomal dominant inheritance. Most pathogenic variants are usually detected in genes for sarcomeric proteins. Nowadays, the genetic basis of HCM is believed to be rather complex. Thousands of mutations in more than 60 genes have been described in association with HCM. Nevertheless, screening large numbers of genes results in the identification of many genetic variants of uncertain significance and makes the interpretation of the results difficult. Patients lacking a pathogenic variant are now believed to have non-Mendelian HCM and probably have a better prognosis than patients with sarcomeric pathogenic mutations. Identifying the genetic basis of HCM creates remarkable opportunities to understand how the disease develops, and by extension, how to disrupt the disease progression in the future. The aim of this review is to discuss the brief history and recent advances in the genetics of HCM and the application of molecular genetic testing into common clinical practice.

• Klíčová slova
• genetics, hypertrophic cardiomyopathy, molecular genetic testing, next-generation sequencing, pathogenic mutations, variants of uncertain significance,
• MeSH
• genetické testování * MeSH
• hypertrofická kardiomyopatie diagnóza   genetika   MeSH
• lidé MeSH
• mutace * MeSH
• sarkomery genetika   MeSH
• svalové proteiny genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• svalové proteiny MeSH

Conflicting results have been published considering the role of head-up tilt test (HUTT) positivity as a prognostic factor in patients with hypertrophic cardiomyopathy (HCM). The relationship between HCM patients' genotype and their HUTT results has not been previously reported. The aim of this study was to evaluate patients with HCM and their HUTT results in regard to its value for outcome prediction and to investigate the relation of patients' genotype and their HUTT results. Seventy-four (51 ± 15 years; 42% women; median follow-up 72 months) HCM patients were divided into two groups based on their HUTT results and were retrospectively analyzed. In 67 (90.5%) subjects included in the analysis, next-generation sequencing-based genomic testing was performed. A composite end point of unexplained syncope, heart failure hospitalization, and death was defined. A total of 14 patients (18.9%) had positive HUTT (HUTT+), whereas 60 (81.1%) had negative HUTT (HUTT-). Except for the New York Heart Association functional class ( p = 0.01), both groups had similar characteristics. Positive genotype was evenly distributed between the two groups. Composite end point occurred in 5 patients (35.7%) in HUTT+ group versus 14 (23.3%) patients in HUTT- group ( p = 0.33). We did not find a relationship between HUTT results and long-term outcome. We found no association between HUTT results and genotype.

• Klíčová slova
• HCM, HOCM, abnormal baroreflex, genotype, head-up tilt test, hypertrophic cardiomyopathy, hypertrophic obstructive cardiomyopathy,
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: The outcome of patients ≥ 60 years of age after alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) remains unresolved. We sought to determine the long-term survival and the causes of death in this population. MATERIAL AND METHODS: We enrolled 156 consecutive patients (69 ±6 years, 69% women, follow-up: 4.8 ±3.5 years) who underwent ASA at ≥ 60 years of age. RESULTS: The 30-day mortality rate was 1.3%. At the last check-up, 81% of patients were in New York Heart Association class ≤ 2 and 76% had a left ventricular outflow tract gradient (LVOG) ≤ 30 mm Hg. A total of 39 patients died (51% of cardiovascular causes, 44% of non-cardiovascular causes, 5% of unknown causes) during the 734 patient-years. The annual sudden mortality, the sudden mortality and the all-cause mortality rates were 0.5%, 1.1%, and 4.8%, respectively. The all-cause mortality was higher compared to the age- and sex-matched general population (p = 0.002). CONCLUSIONS: Alcohol septal ablation was safe and effective in the long-term follow-up. We observed a reduced life expectancy compared to the age- and sex-matched general population. Mortality was almost equally due to cardiovascular and non-cardiovascular causes of death.

• Klíčová slova
• hypertrophic cardiomyopathy, sudden cardiac death, survival,
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: The yield of genetic testing in hypertrophic cardiomyopathy (HCM) is variable. The Mayo HCM Genotype Predictor score (Mayo Score) provides the pre-test probability of a positive HCM genetic test. In the original cohort of Mayo Score patients, only 9 HCM-associated myofilament genes were evaluated. The aim of this study was to validate the Mayo Score in the national HCM cohort and assess the yield of genetic testing using next generation sequencing (NGS) evaluating up to 229 genes. MATERIAL AND METHODS: We included 336 consecutive unrelated HCM patients (41% women, mean age: 53 ±15 years). We performed NGS-based genomic testing with classification of identified variants according to American College of Medical Genetics and Genomics guidelines. NGS findings were compared with the Mayo Score (ranging from -1 to 5) based on clinical and echocardiographic variables. RESULTS: We identified 72 variants classified as pathogenic or likely pathogenic in 70 (21%) HCM patients. One patient with the highest Mayo Score of 5 had a pathogenic mutation (100% yield). Patients with a Mayo Score of 4 had a pathogenic mutation in 71% of cases. Patients with a Mayo Score of 3 or 2 had a pathogenic mutation in 50 and 35% of cases, respectively. The yield of genetic testing in patients with a Mayo Score of -1 to 1 was low (6-21%). CONCLUSIONS: The overall yield of genetic testing using NGS evaluating up to 229 genes was low. The yield of genetic testing was consistently predicted with Mayo Score values.

• Klíčová slova
• diagnostic value, genetic mutations, genetic testing, hypertrophic cardiomyopathy,
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• časopisecké články MeSH

BACKGROUND: The long-term efficacy and safety of alcohol septal ablation (ASA) in patients with highly symptomatic hypertrophic obstructive cardiomyopathy has been demonstrated. The aim of this study was to evaluate the long-term outcomes of mildly symptomatic patients with hypertrophic obstructive cardiomyopathy treated with ASA. METHODS AND RESULTS: We retrospectively evaluated consecutive patients enrolled in the Euro-ASA registry (1427 patients) and identified 161 patients (53±13 years; 27% women) who were mildly symptomatic (New York Heart Association [NYHA] class II) pre-ASA. The median (interquartile range) follow-up was 4.8 (1.7-8.5) years. The clinical outcome was assessed and compared with the age- and sex-matched general population. The 30-day mortality after ASA was 0.6% and the annual all-cause mortality rate was 1.7%, which was similar to the age- and sex-matched general population (P=0.62). A total of 141 (88%) patients had resting left ventricular outflow tract gradient at the last clinical checkup ≤30 mm Hg. Obstruction was reduced from 63±32 to 15±19 mm Hg (P<0.01), and the mean NYHA class decreased from 2.0±0 to 1.3±0.1 (P<0.01); 69%, 29%, and 2% of patients were in NYHA class I, II, and III at the last clinical checkup, respectively. CONCLUSIONS: Mildly symptomatic hypertrophic obstructive cardiomyopathy patients treated with ASA had sustained symptomatic and hemodynamic relief with a low risk of developing severe heart failure. Their survival is comparable to the general population.

• Klíčová slova
• ablation, hypertrophic cardiomyopathy, outcome,
• MeSH
• ablace * škodlivé účinky   mortalita   MeSH
• časové faktory MeSH
• dospělí MeSH
• ethanol aplikace a dávkování   škodlivé účinky   MeSH
• funkce levé komory srdeční MeSH
• hypertrofická kardiomyopatie diagnóza   mortalita   patofyziologie   chirurgie   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• obnova funkce MeSH
• obstrukce výtoku ze srdeční komory diagnóza   mortalita   patofyziologie   chirurgie   MeSH
• proporcionální rizikové modely MeSH
• registrace MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• ethanol MeSH