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The association between genetic polymorphisms and early cardiac allograft vasculopathy (CAV) development is relatively unexplored. Identification of genes involved in the CAV process may offer new insights into pathophysiology and lead to a wider range of therapeutic options.This prospective study of 109 patients investigated 44 single nucleotide polymorphisms (SNPs) within the susceptibility loci potentially related to coronary artery disease, carotid artery intima-media thickness (cIMT), and in nitric oxide synthase gene. Genotyping was done by the Fluidigm SNP Type assays and Fluidigm 48.48 Dynamic Array IFC. The intima thickness progression (IT) was evaluated by coronary optical coherence tomography performed 1 month and 12 months after heart transplantation (HTx).During the first post-HTx year, the mean intima thickness (IT) increased by 24.0 ± 34.2 µm (p0.001) and lumen area decreased by ‒0.9 ± 1.8 mm2 (p0.001). The rs1570360 (A/G) SNP of the vascular endothelial growth factor A (VEGFA) gene showed the strongest association with intima thickness progression, even in the presence of the traditional CAV risk factors. SNPs previously related to carotid artery intima-media thickness rs11785239 (PRAG1), rs6584389 (PAX2), rs13225723 (LINC02577) and rs17477177 (CCDC71L), were among the five most significantly associated with IT progression but lost their significance once traditional CAV risk factors had been added.Results of this study suggest that genetic variability may play an important role in CAV development. The vascular endothelial growth factor A gene SNP rs1570360 showed the strongest association with intima thickness (IT) progression measured by OCT, even in the presence of the traditional CAV risk factors (Tab. 3, Fig. 3, Ref. 36). Text in PDF www.elis.sk Keywords: cardiac allograft vasculopathy, optical coherence tomography, vascular endothelial growth factor A, intimal thickening, genetic polymorphism.

Dilatacni kardiomyopatie a myokarditida jsou spojeny se zvýseným rizikem srdecnich arytmii a jsou jednou z hlavnich přicin nahle srdecni smrti sportovců mladsich 35 let. Adaptace srdce na intenzivni fyzickou zatěž je sama o sobě spojena s řadou elektrických, morfologických a funkcnich změn pod obrazem tzv. atletickeho srdce. Odliseni fyziologicke adaptace od patologickeho nalezu je zcela zasadni pro rizikovou stratifikaci. Cilem teto prace je shrnuti soucasných poznatků v diferencialni diagnostice dilatacni kardiomyopatie a myokarditidy od atletickeho srdce, identifikace jedinců ve vysokem riziku nahle srdecni smrti a shrnuti doporuceni ve vztahu ke sportovni aktivitě. © 2020, CKS.

Aims: Recent-onset dilated cardiomyopathy (RODCM) is a disease of heterogeneous aetiology and clinical outcome. In this pilot study, we aimed to assess its genetic architecture and correlate genotype with left ventricular reverse remodelling (LVRR). Patients and Methods: In this multi-centre prospective observational study, we enrolled 83 Moravian patients with RODCM and a history of symptoms of less than 6 months, for whole-exome sequencing (WES). All patients underwent 12-month clinical and echocardiographic follow-up. LVRR was defined as an absolute increase in left ventricular ejection fraction > 10% accompanied by a relative decrease of left ventricular end-diastolic diameter > 10% at 12 months. Results: WES identified at least one disease-related variant in 45 patients (54%). LVRR occurred in 28 patients (34%), most often in carriers of isolated titin truncated variants, followed by individuals with a negative, or inconclusive WES and carriers of other disease-related variants (56% vs. 42% vs. 19%, P=0.041). Conclusion: A substantial proportion of RODCM cases have a monogenic or oligogenic genetic background. Carriers of non-titin disease-related variants are less likely to reach LVRR at 12- months than other individuals. Genetic testing could contribute to better prognosis prediction and individualized treatment of RODCM.

Left ventricular (LV) involvement in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is not evaluated in the revised Task Force Criteria, possibly leading to underdiagnosis. This study explored the diagnostic role of myocardial native T1 mapping in patients with ARVC and their first-degree relatives. Thirty ARVC patients (47% males, mean age 45 ± 27 years) and 59 first-degree relatives not meeting diagnostic criteria underwent CMR with native T1 mapping. C MR was abnormal in 26 (87%) patients with ARVC. The right ventricle was affected in isolation in 13 (43%) patients. Prior to T1 mapping assessment, 2 (7%) patients exhibited isolated LV involvement and 11 (36%) patients showed features of biventricular disease. Left ventricular involvement was manifest as detectable LV late gadolinium enhancement (LGE) in 12 out of 13 cases. According to pre-specified inter-ventricular septal (IVS) T1 mapping thresholds, 11 (37%) patients revealed raised native T1 values including 5 out of the 17 patients who would otherwise have been classified as exhibiting a normal LV by conventional imaging parameters. Native septal T1 values were elevated in 22 (37%) of the 59 first-degree relatives included. Biventricular involvement is commonly observed in ARVC; native myocardial T1 values are raised in more than one third of patients, including a significant proportion of cases that would have been otherwise classified as exhibiting a normal LV using conventional CMR techniques. The significance of abnormal T1 values in first-degree relatives at risk will need validation through longitudinal studies. Supplementary Information The online version of this article (10.1007/s10554-021-02166-7) contains supplementary material, which is available to authorized users.

Background The aetiology of recent-onset dilated cardiomyopathy (RODCM) includes inflammatory, genetic, toxic and metabolic causes. Delineating the role of inflammation on the genetic background could improve risk stratification. Purpose We aimed to ascertain the role of inflammation evaluated by serum CRP immunohistochemical and PCR analysis of endomyocardial biopsy (EMB) in conjunction with genetic testing in left ventricular reverse remodelling (LVRR) in 12-month follow-up. Methods 83 RODCM patients enrolled in this prospective observational study underwent 12-month echocardiographic follow up whole-exome sequencing, and EMB. Presence of cardiotropic viruses was determined by PCR analysis of the EMB samples. Inflammation was defined according to TIMIC immunohistochemical criteria as the presence of >7 CD3+ lymphocytes/mm2 and/or >14 infiltrating leukocytes (LCA+ cells/mm2). LVRR was defined as an absolute increase in LV ejection fraction > +10% and a relative decrease of LV end-diastolic diameter >−10% at 12 months. Results LVRR occurred in 28 (34%) of all cases. PCR analysis uncovered cardiotropic viruses in 55 (66%) patients, with highest prevalence of parvovirus B19 (47%). (Figure 1) EMB analysis detected inflammation in 28 (34%) cases and inflammation significantly positively predicted LVRR (P=0.019). Sequencing identified disease-related gene variants (ACMG class 3–5) in 45 (54%) patients. Carriers of non-titin gene variants showed a lowest probability of 12-month LVRR (19%) P=0.041. Combination of genetic findings and inflammation did not improve the prediction of LVRR in 12 months. (Table 1) Conclusion Both myocardial inflammation and disease-causing variants can be identified in a large proportion of RODCM cases. Prognostic value of CRP and virus detection is low. Non-titin disease-related variants carriers of are less likely to reach LVRR. In contrast, myocardial inflammation detected by EMB predicts favourable remodelling in 12 months. Figure 1 Funding Acknowledgement Type of funding source: None

Cil: Hypertroficka kardiomyopatie (HKMP) je poměrně caste, geneticky podminěne srdecni onemocněni (vyskytujici se s prevalenci 1 : 500), ktere je ve svem klinickem obraze, prognoze a lecebných strategiich znacně heterogenni. Jako takove casto představuje dilema jak pro lekaře primarni pece, tak pro kardiology a kardiochirurgy. S ohledem na různorode možnosti lecby zminěneho onemocněni je důležite popisovat relevantni kasuistiky přispivajici k vyjasněni casto obtižných otazek, jež v teto souvislosti mohou vyvstat.Metody/prezentace kasuistiky: Popisujeme připad 74lete ženy s vysoce symptomatickou obstrukcni hypertrofickou kardiomyopatii (HOKMP) a souběžným výskytem mirne, hemodynamicky nevýznamne stenoinsuficience aortalni chlopně. Pacientka trpěla omezujicimi symptomy, jež nereagovaly ani na maximalni farmakoterapii, a byla odeslana do naseho centra k navrženi optimalni intervencni lecebne strategie.Výsledky: Pacientka podstoupila alkoholovou septalni ablaci s dobrým bezprostřednim, lec suboptimalnim dlouhodobým klinickým ucinkem. Během jednoho roku vstupně nevýznamna aortalni stenoza progredovala a zaroveň doslo k znovu obnoveni hypertrofie septa; proto bylo přistoupeno ke kombinovane chirurgicke septalni myektomii a nahradě aortalni chlopně a posleze i k nahradě mitralni chlopně kvůli peroperacni komplikaci. Vysetřeni s odstupem jednoho roku potvrdilo optimalni lecebný ucinek tohoto postupu. V Evropě se alkoholova septalni ablace stala u pacientů se symptomatickou HOKMP upřednostňovanou vstupni intervencni metodou, což se vztahuje zejmena na starsi pacienty s přidruženými onemocněnimi. Nase kasuistika doklada, že chirurgicka septalni myektomie doplněna plastikou ci nahradou chlopni může pro vybrane pacienty představovat metodu volby.Zavěr: Chtěli bychom zdůraznit důležitost vhodneho výběru pacientů pro danou intervenci v ramci tohoto heterogenniho spektra onemocněni, zejmena u pacientů s kombinaci HOKMP a postiženi chlopni, a nezbytnost spravneho posouzeni vhodne lecebne strategie pro každeho jednotliveho nemocneho.

Background Recent-onset dilated cardiomyopathy (RODCM) is a disease of heterogeneous aetiology including genetic, inflammatory, toxic and metabolic causes. Recognition of the genetic component could improve diagnostic management and risk stratification. Left ventricular reverse remodelling (LVRR) has been identified as a marker of favourable prognosis in RODCM. Purpose In this pilot study, we are first to assess the genetic background of RODCM in the Czech Republic by whole-exome sequencing and correlate genotype with LV reverse remodelling. Methods In this multi-centre prospective observational study, we enrolled 83 patients with RODCM and a history of symptoms of less than 6 months, for whole-exome sequencing. All patients underwent 12-month clinical and echocardiographic follow-up. LVRR was defined as an absolute increase in left ventricular ejec-tion fraction >10% accompanied by a relative decrease of left ventricular end-diastolic diameter >10% at 12 months. Results Whole-exome sequencing identified at least one disease-related variant in 45 patients (54%). As expected, the gene spectrum of identified variants in RODCM was quite wide comprising a total of 28 different genes, with the majority of truncating variants in titin gene which was found in 10 (12%) patients. LVRR occurred in 28 patients (34%), most often in carriers of isolated titin truncating variants, followed by individuals with a negative, or inconclusive results and carriers of other disease-related variants (56% vs. 42% vs. 19%, P 0.041). Genotype and LVRR Exom negative or non conclusive Isolated titin truncating variant Other variant or combination P-value (n=38) (n=9) (n=36) 12 months ΔLVEF absolute (%) 16 (6–23) 15 (9–34) 6 (3–15) 0.036* 12 months ΔLVEF >10% (n=44; 53%) 24 (63%) 7 (78%) 13 (36%) 0.019* 12 months ΔLVEDD 10% and ΔLVEDD Gene distribution in RODCM Conclusion A substantial proportion of RODCM cases has genetic background. Carriers of titin truncating variants are more likely to reach LVRR at 12 months, which could be seen as a positive prognostic marker of disease development. Genetic testing could contribute to better prognosis prediction and individualised treatment of patients with RODCM. Acknowledgement/Funding This study was supported by the research grant of the Ministry of Health, Czech Republic: MZ 15-27682A. All rights reserved.