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.

Atherothrombotic diseases (ATEs) and venous thromboembolism (VTE) have been traditionally considered to have a distinct pathogenesis. Today, a growing body of evidence on the pathophysiology of thrombus formation has convincingly proved that they share more mutual risk factors than previously recognized. It has been shown in a number of case‑control studies that there is a significant risk for a subsequent cardiovascular disease after VTE, although this risk is low or at most moderate. In the past 2 decades, the role of each inherited risk factor for VTE in relation to ATE has been intensively studied. Unfortunately, a large body of contradictory findings has been published that hinders consensus and transformation of knowledge into clinical practice. Complicated gene‑gene interactions, small sample sizes, heterogeneous genetic and environmental patient backgrounds, confounding factors, and varied methodological designs may have contributed to opposing findings. In the case of rare thrombophilias, conclusions must be summarized based on case reports or case series, as only few case‑control and cohort studies are available. In this review we focus on available evidence and controversies regarding the relationship between the classic inherited VTE risk factors (factor V Leiden, prothrombin 20210A, deficiencies of antithrombin, protein C, and protein S) and the risk of myocardial infarction (MI). We conclude that the risk of MI in patients with common inherited thrombophilia is generally modest. However, in patients with deficiencies of antithrombin, protein C, or protein S, the risk of MI or other ATEs is not negligible. A personalized clinical approach is suggested when testing for inherited thrombophilia in a patient with MI.

Aspirin resistance established by different laboratory methods is still a debated problem. Using COX1 specific methods no aspirin resistance was detected among healthy volunteers. Here we tested the effect of chronic aspirin treatment on platelets from patients with stable coronary artery disease. The expression of COX2 mRNA in platelets and its influences on the effect of aspirin was also investigated. One hundred and forty four patients were enrolled in the study. The direct measurement of COX1 acetylation was carried out by monoclonal antibodies specific to acetylated and non-acetylated COX1 (acCOX1 and nacCOX1) using Western blotting technique. Arachidonic acid (AA) induced TXB2 production by platelets was measured by competitive immunoassay. AA induced platelet aggregation, ATP secretion and VerifyNow Aspirin Assay were also performed. COX2 and COX1 mRNA expression in platelets were measured in 56 patients by RT-qPCR. In 138 patients only acCOX1 was detected, in the remaining six patients nacCOX1 disappeared after a compliance period. AA induced TXB2 production by platelets was very low in all patients including the 6 patients after compliance. AA induced platelet aggregation, secretion and with a few exceptions the VerifyNow Assay also demonstrated the effect of aspirin. Smoking, diabetes mellitus and inflammatory conditions did not influence the results. The very low amount of COX2 mRNA detected in 39 % of the investigated platelets did not influence the effect of aspirin. No aspirin resistance was detected among patients with stable coronary artery disease. COX2 expression in platelets did not influence the effect of aspirin.

The structure of aspirated coronary thrombus in ST-segment elevation myocardial infarction (STEMI) is still being studied. Our aims were to characterize coronary thrombi of different ages, focusing on the appearance of activated protein C (APC/PC) and its relation to the elements of neutrophil extracellular traps (NETs), and the factors closely related to fibrin as factor XIII (FXIII) and α2 plasmin inhibitor (α2-PI). The thrombi of n = 24 male patients with atherosclerotic coronary plaque rupture related to native coronary artery occlusion were selected for histopathology analysis. Thrombus age was distinguished as fresh, lytic, and organized, and then analyzed by immunofluorescent staining and confocal microscopy. FXIII was present at a high level and showed a high degree of co-localization with fibrin in all stages of thrombus evolution. The amount of α2-PI was low in the fresh thrombi, which increased significantly to the lytic phase. It was evenly distributed and consistently associated with fibrin. APC/PC appeared in the fresh thrombus and remained constant during its evolution. The presence of NET marker and CD66b was most dominant in the lytic phase. APC/PC co-localization with the elements of NET formation shows its role in NET degradation. These observations suggest the importance of searching for further targeted therapeutic strategies in STEMI patients.

Atrial fibrillation (AF) is the most common arrhythmia in myocardial infarction (MI). AF can be caused by ischemia, and MI can be caused by AF. Additionally, 4–5% of MI cases are related to coronary embolism (CE), and one-third of cases are attributed to AF. Our aim was to investigate the prevalence of AF-related CE cases among 3 consecutive years of STEMI cases. We also aimed to reveal the diagnostic accuracy of the Shibata criteria scoring system and the role of thrombus aspiration. Among 1181 STEMI patients, 157 had AF (13.2%). By using the Shibata’s diagnostic criteria, 10 cases were classified as ‘definitive’ and 31 as ‘probable’ CE. After re-evaluation, a further five cases were classified as ‘definitive’. Further analysis of the 15 CE cases revealed that CE was more prevalent in patients with previously known (n = 10) compared to those with new-onset (n = 5) AF (16.7% vs. 5.1%, p = 0.024). A PubMed search was performed, and 40 AF-related cases were found where the Shibata’s criteria could be applied. Further, 31 cases could be classified as ‘definitive’, 4 as ‘probable’ and, in 5 cases, the embolic origin could be excluded. In 40% of reported cases and in 47% of our cases, thrombus aspiration helped in diagnosis.