BACKGROUND: Although genetic variants in MYH7 are the most frequent cause of pediatric genetic dilated cardiomyopathy (DCM), there are no studies available describing this entity. We sought to describe clinical features, analyze variant location, and explore predictors of bad prognosis in pediatric MYH7-related DCM. METHODS AND RESULTS: We evaluated clinical records from 44 patients (24 men; median age at diagnosis, 0.54 [interquartile range, 0.01-10.8] years) with pathogenic/likely pathogenic variants in MYH7 diagnosed with DCM at pediatric age (<18 years) followed at 13 international centers. We also explored risk factors associated with a composite end point of end-stage heart failure defined as heart transplantation or heart failure-related death. Twenty-two patients (50%) were diagnosed at age <6 months, including 7 (16%) at birth. Left ventricular (LV) hypertrabeculation features were present in 15 (38%), particularly among patients with genetic variants in the head domain. After a median follow-up of 6.1 years (interquartile range, 1.9-13.4), 15 patients (36%) required a heart transplant (n=14) or died due to end-stage heart failure (n=1), 15 patients (36%) persisted with systolic dysfunction despite treatment, 12 (29%) had a significant increase in LV ejection fraction, and 2 were lost to follow-up. Overall, end-stage heart failure event rate was 25% at 5 years. New York Heart Association class III to IV (hazard ratio [HR], 7.67 [95% CI, 2.16-27.2]; P=0.002) and LV ejection fraction ≤35% (HR, 4.00 [95% CI, 1.11-14.4]; P=0.03) were the best predictors of bad prognosis. CONCLUSIONS: Pediatric MYH7-related DCM is characterized by early onset, frequent LV hypertrabeculation, and poor prognosis. Advanced New York Heart Association class and low LV ejection fraction emerged as predictors of end-stage heart failure.

• MeSH
• dilatační kardiomyopatie * genetika   patofyziologie   diagnóza   MeSH
• dítě MeSH
• fenotyp MeSH
• funkce levé komory srdeční MeSH
• genetická predispozice k nemoci MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mutace MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• srdeční myosiny * genetika   MeSH
• srdeční selhání genetika   patofyziologie   diagnóza   MeSH
• těžké řetězce myosinu * genetika   MeSH
• transplantace srdce * MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: Heart transplantation (HTx) is an established therapeutic option for children with end-stage heart failure. Comprehensive pediatric nationwide HTx program was introduced in 2014 in the Czech Republic. The aim of this study was to evaluate its mid-term characteristics and outcomes and to compare them with international data. METHODS: Retrospective observational study, including all patients who underwent HTx from June 2014 till December 2022. Data from the institutional database were used for descriptive statistics and survival analyses. RESULTS: A total of 30 HTx were performed in 29 patients with congenital heart disease (CHD, N = 15, single ventricular physiology in 10 patients) and cardiomyopathy (CMP, N = 14). Ten patients were bridged to HTx by durable left ventricular assist devices (LVADs) for a mean duration of 104 (SD 89) days. There was one early and one late death during median follow-up of 3.3 (IQR 1.3-6.1) years. Survival probability at 5 years after HTx was 93%. Two patients underwent re-transplantation (one of them in an adult center). Significant rejection-free survival at 1, 3, and 6 years after HTx was 76%, 63%, and 63%, respectively. CONCLUSIONS: The introduced pediatric HTx program reflects the complexity of the treated population, with half of the patients having complex CHD and one-third being bridged to HTx by LVADs. Mid-term results are comparable to worldwide data. The data confirm the possibility of establishing a successful nationwide pediatric HTx program in a relatively small population country with well-developed pediatric cardiovascular care and other transplantation programs.

• MeSH
• dítě MeSH
• dospělí MeSH
• kardiomyopatie * MeSH
• lidé MeSH
• podpůrné srdeční systémy * MeSH
• retrospektivní studie MeSH
• srdeční selhání * chirurgie   MeSH
• transplantace srdce * MeSH
• vrozené srdeční vady * MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: The HeartMate 3 (HM 3; Abbott) left ventricular assist device (LVAD) has improved hemocompatibility-related adverse outcomes. In sporadic cases, external compression of the outflow graft causing obstruction (eOGO) can result from substance accumulation between the outflow graft and its bend relief. We sought to evaluate the prevalence, course, and clinical implications of eOGO in an international study. METHODS: A multicenter retrospective analysis of HM 3 LVADs implanted between November 2014 and April 2021 (n = 2108) was conducted across 17 cardiac centers in 8 countries. We defined eOGO as obstruction >25% in the cross-sectional area in imaging (percutaneous angiography, computed tomography, or intravascular ultrasound). The prevalence and annual incidence were calculated. Serious adverse events and outcomes (death, transplantation, or device exchange) were analyzed for eOGO cases. RESULTS: Of 2108 patients, 62 were diagnosed with eOGO at a median LVAD support duration of 953 (interquartile range, 600-1267) days. The prevalence of eOGO was 3.0% and the incidence at 1, 2, 3, 4, and 5 years of support was 0.6%, 2.8%, 4.0%, 5.2%, and 9.1%, respectively. Of 62 patients, 9 were observed, 27 underwent surgical revision, 15 underwent percutaneous stent implantation, 8 received a heart transplant, and 2 died before intervention. One patient underwent surgical revision and later stent implantation. The mortality with therapeutic intervention was 9/53 (17.0%). CONCLUSIONS: Although uncommon, HM 3 LVAD-supported patients might develop eOGO with an increasing incidence after 1 year of support. Although engineering efforts to reduce this complication are under way, clinicians must maintain a focus on early detection and remain vigilant.

• MeSH
• lidé MeSH
• počítačová rentgenová tomografie MeSH
• podpůrné srdeční systémy * škodlivé účinky   MeSH
• retrospektivní studie MeSH
• srdeční selhání * MeSH
• transplantace srdce * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: Plasma donor-derived cell-free DNA (dd-cfDNA) is used to screen for rejection in heart transplants. We launched the Trifecta-Heart study ( ClinicalTrials.gov No. NCT04707872), an investigator-initiated, prospective trial, to examine the correlations between genome-wide molecular changes in endomyocardial biopsies (EMBs) and plasma dd-cfDNA. The present report analyzes the correlation of plasma dd-cfDNA with gene expression in EMBs from 4 vanguard centers and compared these correlations with those in 604 kidney transplant biopsies in the Trifecta-Kidney study ( ClinicalTrials.gov No. NCT04239703). METHODS: We analyzed 137 consecutive dd-cfDNA-EMB pairs from 70 patients. Plasma %dd-cfDNA was measured by the Prospera test (Natera Inc), and gene expression in EMBs was assessed by Molecular Microscope Diagnostic System using machine-learning algorithms to interpret rejection and injury states. RESULTS: Top transcripts correlating with dd-cfDNA were related to genes increased in rejection such as interferon gamma-inducible genes (eg, HLA-DMA ) but also with genes induced by injury and expressed in macrophages (eg, SERPINA1 and HMOX1 ). In gene enrichment analysis, the top dd-cfDNA-correlated genes reflected inflammation and rejection pathways. Dd-cfDNA correlations with rejection genes in EMB were similar to those seen in kidney transplant biopsies, with somewhat stronger correlations for TCMR genes in hearts and ABMR genes in kidneys. However, the correlations with parenchymal injury-induced genes and macrophage genes were much stronger in hearts. CONCLUSIONS: In this first analysis of Trifecta-Heart study, dd-cfDNA correlates significantly with molecular rejection but also with injury and macrophage infiltration, reflecting the proinflammatory properties of injured cardiomyocytes. The relationship supports the utility of dd-cfDNA in clinical management of heart transplant recipients.

• MeSH
• biologické markery krev   MeSH
• biopsie MeSH
• dárci tkání * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• myokard * patologie   metabolismus   MeSH
• prediktivní hodnota testů MeSH
• prospektivní studie MeSH
• rejekce štěpu * genetika   imunologie   patologie   krev   diagnóza   MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• transplantace ledvin škodlivé účinky   MeSH
• transplantace srdce * škodlivé účinky   MeSH
• volné cirkulující nukleové kyseliny * krev   genetika   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
• srovnávací studie MeSH

Ortotopická transplantace srdce (OTS) je léčebná metoda pacientů v terminální fázi srdečního selhání, u kterých byly vyčerpány všechny farmakologické i nefarmakologické léčebné postupy. Vybrat vhodného pacienta k provedení srdeční transplantace a zvolit vhodný okamžik výkonu je velmi komplexní rozhodnutí. Pacient musí splňovat jednak indikační kritéria, jednak nesmí mít kontraindikace. Sledování pacientů po OTS zahrnuje v prvních 1–2 letech po operaci plánované endomyokardiální biopsie k odhalení rejekce. Dále se pravidelně provádí echokardiografie a laboratorní vyšetření zaměřené nejen na hodnocení koncentrací imunosupresiv. Koronarografie slouží k odhalení vaskulopatie štěpu. Pacient musí doživotně užívat imunosupresivní léčbu, u níž je snaha o maximální individualizaci, ale která přesto s sebou přináší četné komplikace. Pacienti po úspěšné OTS se však vracejí do plnohodnotného a kvalitního života. Nové technologie a postupy v transplantačním programu jsou stále předmětem širokého výzkumu.

Orthotopic heart transplantation (OTS) is a method for patients in the terminal stage of chronic heart failure, for whom all pharmacological and non‐pharmacological treatments have been used. Choosing the right patient for a heart transplant and choosing the right moment for the procedure is a very complex decision. The patient must meet the indication criteria, and must not have any contraindications. Planned endomyocardial biopsies to detect rejection are carried in the first 1‐2 years after surgery. In addition, echocardiography, laboratory tests and other specialized methods are regularly performed. Coronary angiography serves to detect graft vasculopathy. The patient has to take individualized immunosuppressive treatment for the rest of his or her life despite the risk of numerous complications. However, patients after successful OTS return to a full and quality life. New technologies and procedures in the transplant program are still the subject of extensive research.

• MeSH
• imunosupresivní léčba metody   škodlivé účinky   MeSH
• lidé MeSH
• pooperační komplikace klasifikace   MeSH
• příprava pacienta k transplantaci metody   MeSH
• rejekce štěpu klasifikace   MeSH
• srdeční selhání chirurgie   terapie   MeSH
• transplantace srdce * klasifikace   metody   škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

AIMS: Patients with heart failure (HF) display metabolic alterations, including heightened ketogenesis, resulting in increased beta-hydroxybutyrate (β-OHB) formation. We aimed to investigate the determinants and prognostic impact of circulating β-OHB levels in patients with advanced HF and reduced ejection fraction (HFrEF). METHODS AND RESULTS: A total of 867 patients with advanced HFrEF (age 57 ± 11 years, 83% male, 45% diabetic, 60% New York Heart Association class III), underwent clinical and echocardiographic examination, circulating metabolite assessment, and right heart catheterization (n = 383). The median β-OHB level was 64 (interquartile range [IQR] 33-161) μmol/L (normal 0-74 μmol/L). β-OHB levels correlated with increased markers of lipolysis (free fatty acids [FFA]), higher natriuretic peptides, worse pulmonary haemodynamics, and lower humoral regulators of ketogenesis (insulin/glucagon ratio). During a median follow-up of 1126 (IQR 410-1781) days, there were 512 composite events, including 324 deaths, 81 left ventricular assist device implantations and 107 urgent cardiac transplantations. In univariable Cox regression, increased β-OHB levels (T3 vs. T1: hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.13-1.72, p = 0.002) and elevated FFA levels (T3 vs. T1: HR 1.39, 95% CI 1.09-1.79, p = 0.008) were both predictors of a worse prognosis. In multivariable Cox analysis evaluating the simultaneous associations of FFA and β-OHB levels with outcomes, only FFA levels remained significantly associated with adverse outcomes. CONCLUSIONS: In patients with advanced HFrEF, increased plasma β-OHB correlate with FFA levels, worse right ventricular function, greater neurohormonal activation and other markers of HF severity. The association between plasma β-OHB and adverse outcomes is eliminated after accounting for FFA levels, suggesting that increased β-OHB is a consequence reflecting heightened lipolytic state, rather than a cause of worsening HF.

• MeSH
• biologické markery * krev   MeSH
• echokardiografie MeSH
• kyselina 3-hydroxymáselná * krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• senioři MeSH
• srdeční katetrizace MeSH
• srdeční selhání * krev   patofyziologie   MeSH
• tepový objem * fyziologie   MeSH
• transplantace srdce MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The genetic basis of hypertrophic cardiomyopathy (HCM) is complex, and the relationship between genotype status and clinical outcome is incompletely resolved. METHODS AND RESULTS: We assessed a large international HCM cohort to define in contemporary terms natural history and clinical consequences of genotype. Consecutive patients (n=1468) with established HCM diagnosis underwent genetic testing. Patients with pathogenic (or likely pathogenic) variants were considered genotype positive (G+; n=312; 21%); those without definite disease-causing mutations (n=651; 44%) or variants of uncertain significance (n=505; 35%) were considered genotype negative (G-). Patients were followed up for a median of 7.8 years (interquartile range, 3.5-13.4 years); HCM end points were examined by cumulative event incidence. Over follow-up, 135 (9%) patients died, 33 from a variety of HCM-related causes. After adjusting for age, all-cause and HCM-related mortality did not differ between G- versus G+ patients (hazard ratio [HR], 0.78 [95% CI, 0.46-1.31]; P=0.37; HR, 0.93 [95% CI, 0.38-2.30]; P=0.87, respectively). Adverse event rates, including heart failure progression to class III/IV, heart transplant, or heart failure death, did not differ (G- versus G+) when adjusted for age (HR, 1.20 [95% CI, 0.63-2.26]; P=0.58), nor was genotype independently associated with sudden death event risk (HR, 1.39 [95% CI, 0.88-2.21]; P=0.16). In multivariable analysis, age was the only independent predictor of all-cause and HCM-related mortality, heart failure progression, and sudden death events. CONCLUSIONS: In this large consecutive cohort of patients with HCM, genotype (G+ or G-) was not a predictor of clinical course, including all-cause and HCM-related mortality and risk for heart failure progression or sudden death. G+ status should not be used to dictate clinical management or predict outcome in HCM.

• MeSH
• časové faktory MeSH
• dospělí MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• genetické testování metody   MeSH
• genotyp * MeSH
• hypertrofická kardiomyopatie * genetika   mortalita   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• náhlá srdeční smrt etiologie   epidemiologie   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• rizikové faktory MeSH
• senioři MeSH
• srdeční selhání genetika   mortalita   MeSH
• transplantace srdce 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

• MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• srdeční selhání * epidemiologie   etiologie   prevence a kontrola   terapie   MeSH
• transplantace srdce MeSH
• Publikační typ
• rozhovory MeSH
• Geografické názvy
• Česká republika MeSH

• MeSH
• dějiny 20. století MeSH
• dějiny lékařství * MeSH
• hrudní chirurgie dějiny   MeSH
• kardiochirurgické výkony dějiny   MeSH
• srdeční selhání chirurgie   dějiny   MeSH
• transplantace srdce * dějiny   MeSH
• Check Tag
• dějiny 20. století MeSH
• Publikační typ
• biografie MeSH
• historické články MeSH
• Geografické názvy
• Jihoafrická republika MeSH

• O autorovi
• Barnard, Christiaan Neethling, 1922-2001 Autorita

BACKGROUND: There is conflicting evidence on the role of acetylsalicylic acid (ASA) use in the development of cardiac allograft vasculopathy (CAV). METHODS: A nationwide prospective two-center study investigated changes in the coronary artery vasculature by highly automated 3-D optical coherence tomography (OCT) analysis at 1 month and 12 months after heart transplant (HTx). The influence of ASA use on coronary artery microvascular changes was analyzed in the overall study cohort and after propensity score matching for selected clinical CAV risk factors. RESULTS: In total, 175 patients (mean age 52 ± 12 years, 79% male) were recruited. During the 1-year follow-up, both intimal and media thickness progressed, with ASA having no effect on its progression. However, detailed OCT analysis revealed that ASA use was associated with a lower increase in lipid plaque (LP) burden (p = .013), while it did not affect the other observed pathologies. Propensity score matching of 120 patients (60 patient pairs) showed similar results, with ASA use associated with lower progression of LPs (p = .002), while having no impact on layered fibrotic plaque (p = .224), calcification (p = .231), macrophage infiltration (p = .197), or the absolute coronary artery risk score (p = .277). According to Kaplan-Meier analysis, ASA use was not associated with a significant difference in survival (p = .699) CONCLUSION: This study showed a benefit of early ASA use after HTx on LP progression. However, ASA use did not have any impact on the progression of other OCT-observed pathologies or long-term survival.

• MeSH
• alografty patologie   MeSH
• aterosklerotický plát * komplikace   MeSH
• dospělí MeSH
• koronární angiografie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci koronárních tepen * etiologie   MeSH
• optická koherentní tomografie škodlivé účinky   metody   MeSH
• prospektivní studie MeSH
• transplantace srdce * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH