Hypertrophic cardiomyopathy (HCM) is a primary disease of the myocardium most commonly caused by mutations in sarcomeric genes. We aimed to perform a nationwide large-scale genetic analysis of a previously unreported, representative HCM cohort in Hungary. A total of 242 consecutive HCM index patients (127 men, 44 ± 11 years) were studied with next generation sequencing using a custom-designed gene-panel comprising 98 cardiomyopathy-related genes. A total of 90 patients (37%) carried pathogenic/likely pathogenic (P/LP) variants. The percentage of patients with P/LP variants in genes with definitive evidence for HCM association was 93%. Most of the patients with P/LP variants had mutations in MYBPC3 (55 pts, 61%) and in MYH7 (21 pts, 23%). Double P/LP variants were present in four patients (1.7%). P/LP variants in other genes could be detected in ≤3% of patients. Of the patients without P/LP variants, 46 patients (19%) carried a variant of unknown significance. Non-HCM P/LP variants were identified in six patients (2.5%), with two in RAF1 (p.Leu633Val, p.Ser257Leu) and one in DES (p.Arg406Trp), FHL1 (p.Glu96Ter), TTN (p.Lys23480fs), and in the mitochondrial genome (m.3243A>G). Frameshift, nonsense, and splice-variants made up 82% of all P/LP MYBPC3 variants. In all the other genes, missense mutations were the dominant form of variants. The MYBPC3 p.Gln1233Ter, the MYBPC3 p.Pro955ArgfsTer95, and the MYBPC3 p.Ser593ProfsTer11 variants were identified in 12, 7, and 13 patients, respectively. These three variants made up 36% of all patients with identified P/LP variants, raising the possibility of a possible founder effect for these mutations. Similar to other HCM populations, the MYBPC3 and the MYH7 genes seemed to be the most frequently affected genes in Hungarian HCM patients. The high prevalence of three MYBPC3 mutations raises the possibility of a founder effect in our HCM cohort.

Although the clinical manifestations of SARS-CoV-2 viral infection affect mainly the respiratory system, cardiac complications are common and are associated with increased morbidity and mortality. While echocardiographic alterations indicating myocardial involvement are widely reported in patients hospitalized for acute COVID-19 infection, much fewer data available in non-hospitalized, mildly symptomatic COVID-19 patients. In our work, we aimed to investigate subclinical cardiac alterations characterized by parameters provided by advanced echocardiographic techniques following mild SARS-CoV-2 viral infection. A total of 86 patients (30 males, age: 39.5 ± 13.0 yrs) were assessed 59 ± 33 days after mild SARS-CoV-2 viral infection (requiring no hospital or <5 days in-hospital treatment) by advanced echocardiographic examination including 2-dimensional (2D) speckle tracking echocardiography and non-invasive myocardial work analysis, and were compared to an age-and sex-matched control group. Altogether, variables from eleven echocardiographic categories representing morphological or functional echocardiographic parameters showed statistical difference between the post-COVID patient group and the control group. The magnitude of change was subtle or mild in the case of these parameters, ranging from 1–11.7% of relative change. Among the parameters, global longitudinal strain [−20.3 (−21.1–−19.0) vs. −19.1 (−20.4–−17.6) %; p = 0.0007], global myocardial work index [1975 (1789–2105) vs. 1829 (1656–2057) Hgmm%; p = 0.007] and right ventricular free wall strain values (−26.6 ± 3.80 vs. −23.8 ± 4.0%; p = 0.0003) showed the most significant differences between the two groups. Subclinical cardiac alterations are present following even mild SARS-CoV-2 viral infection. These more subtle alterations are difficult to detect by routine echocardiography. Extended protocols, involving speckle-tracking echocardiography, non-invasive measurement of cardiac hemodynamics, and possibly myocardial work are necessary for detection and adequate follow-up.

Background: Variant transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited disease, where the mutation of the transthyretin gene (TTR) results in the deposition of pathogenic protein fibrils in various tissues. The mutation type influences the clinical course. Until now, no data were available on the genotype, phenotype, and prevalence of Hungarian ATTRv patients. The aim of our study was to assess the prevalence, regional distribution, genotypes, and phenotypes of Hungarian patients with ATTRv. Methods: With the collaboration of Hungarian regional and university centers, we identified patients diagnosed with ATTRv. We also searched prior publications for case studies of Hungarian ATTRv patients. Results: 40 individuals in 23 families with ATTRv were identified within the borders of Hungary. At the time of the diagnosis, 24 of them were symptomatic. The two most common mutations were ATTRHis88Arg (nine families) and ATTRIle107Val (8 families). ATTRVal30Met was demonstrated in 2 families, and ATTRVal122del, ATTRPhe33Leu, ATTRIle84Ser, and ATTRAsp18Gly in one family each. The median age of the symptomatic patients at the time of clinical diagnosis was 65 years. The most common clinically significant organ involvement was restrictive cardiomyopathy, found in 24 patients. Polyneuropathy was diagnosed in 20 patients. A total of 19 patients showed a mixed phenotype. The leading symptom was heart failure in 8 cases (3 of them had only cardiac symptoms), polyneuropathy in 11 cases (all of them also had cardiac symptoms), and equally severe cardiac and neuropathy symptoms were present in 3 cases. Out of 24 symptomatic patients, 10 received targeted pharmacological therapy. The follow-up period ranged from 1 to 195 months. At the time of the retrospective analysis, 12 patients had already died, and 1 patient underwent heart transplantation. Conclusions: As TTR genotype influences the phenotype and clinical course of ATTRv, it is important to know the regional data. In Hungary, ATTRHis88Arg and ATTRIle107Val are the most common mutations in ATTRv, both presenting with mixed phenotype, but the median age at the time of the diagnosis is 9 years lower in patients with ATTRHis88Arg than in patients with ATTRIle107Val.

A szívamyloidosis egy súlyos, progresszív, infiltratív betegség, amelyet amiloidfibrillumok szívizomban való lerakódása okoz. Hátterében általában hematológiai, krónikus gyulladásos betegségek, illetve genetikai eltérések állhatnak, de az időskorban jellemző forma esetében a pontos ok ismeretlen. Az utóbbi években a modern képalkotó eljárásoknak és a noninvazív diagnosztika lehetőségének, valamint az egyre több, hatásos betegség specifikus terápiának köszönhetően növekszik a diagnosztizált esetek száma, így feltételezhetően a kórkép a korábban gondolthoz képest gyakoribb eltérés lehet. Sorra jelentek meg a diagnosztikus és terápiás algoritmusok a közelmúltban, így 2021-ben az ESC Myocardial and Pericardial Diseases Munkacsoportja egy áttekintő közleményt adott ki a jelenleg alkalmazandó irányelvekről.