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.

• Klíčová slova
• MYH7, dilated cardiomyopathy, genetics, pediatric,
• 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
• Názvy látek
• MYH7 protein, human MeSH Prohlížeč
• srdeční myosiny * MeSH
• těžké řetězce myosinu * MeSH

Cardiac myosin-specific (MyHC) T cells drive the disease pathogenesis of immune checkpoint inhibitor-associated myocarditis (ICI-myocarditis). To determine whether MyHC T cells are tissue-resident memory T (TRM) cells, we characterized cardiac TRM cells in naive mice and established that they have a distinct phenotypic and transcriptional profile that can be defined by their upregulation of CD69, PD-1, and CXCR6. We then investigated the effects of cardiac injury through a modified experimental autoimmune myocarditis mouse model and an ischemia-reperfusion injury mouse model and determined that cardiac inflammation induces the recruitment of autoreactive MyHC TRM cells, which coexpress PD-1 and CD69. To investigate whether the recruited MyHC TRM cells could increase susceptibility to ICI-myocarditis, we developed a two-hit ICI-myocarditis mouse model where cardiac injury was induced, mice were allowed to recover, and then were treated with anti-PD-1 antibodies. We determined that mice who recover from cardiac injury are more susceptible to ICI-myocarditis development. We found that murine and human TRM cells share a similar location in the heart and aggregate along the perimyocardium. We phenotyped cells obtained from pericardial fluid from patients diagnosed with dilated cardiomyopathy and ischemic cardiomyopathy and established that pericardial T cells are predominantly CD69+ TRM cells that up-regulate PD-1. Finally, we determined that human pericardial macrophages produce IL-15, which supports and maintains pericardial TRM cells.

• Klíčová slova
• ICI-myocarditis, PD-1, cardiac immunology, tissue-resident memory T cells,
• MeSH
• antigeny CD279 metabolismus   MeSH
• CD antigeny MeSH
• diferenciační antigeny T-lymfocytů metabolismus   imunologie   MeSH
• inhibitory kontrolních bodů * farmakologie   MeSH
• lektiny typu C metabolismus   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myokard imunologie   patologie   metabolismus   MeSH
• myokarditida * imunologie   patologie   metabolismus   MeSH
• myosiny metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• paměťové T-buňky * imunologie   metabolismus   MeSH
• srdeční myosiny imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD279 MeSH
• CD antigeny MeSH
• CD69 antigen MeSH Prohlížeč
• diferenciační antigeny T-lymfocytů MeSH
• inhibitory kontrolních bodů * MeSH
• lektiny typu C MeSH
• myosiny MeSH
• Pdcd1 protein, mouse MeSH Prohlížeč
• srdeční myosiny MeSH

Adverse remodelling following an initial insult is the hallmark of heart failure (HF) development and progression. It is manifested as changes in size, shape, and function of the myocardium. While cardiac remodelling may be compensatory in the short term, further neurohumoral activation and haemodynamic overload drive this deleterious process that is associated with impaired prognosis. However, in some patients, the changes may be reversed. Left ventricular reverse remodelling (LVRR) is characterized as a decrease in chamber volume and normalization of shape associated with improvement in both systolic and diastolic function. LVRR might occur spontaneously or more often in response to therapeutic interventions that either remove the initial stressor or alleviate some of the mechanisms that contribute to further deterioration of the failing heart. Although the process of LVRR in patients with new-onset HF may take up to 2 years after initiating treatment, there is a significant portion of patients who do not improve despite optimal therapy, which has serious clinical implications when considering treatment escalation towards more aggressive options. On the contrary, in patients that achieve delayed improvement in cardiac function and architecture, waiting might avoid untimely implantable cardioverter-defibrillator implantation. Therefore, prognostication of successful LVRR based on clinical, imaging, and biomarker predictors is of utmost importance. LVRR has a positive impact on prognosis. However, reverse remodelled hearts continue to have abnormal features. In fact, most of the molecular, cellular, interstitial, and genome expression abnormalities remain and a susceptibility to dysfunction redevelopment under biomechanical stress persists in most patients. Hence, a distinction should be made between reverse remodelling and true myocardial recovery. In this comprehensive review, current evidence on LVRR, its predictors, and implications on prognostication, with a specific focus on HF patients with non-ischaemic cardiomyopathy, as well as on novel drugs, is presented.

• Klíčová slova
• Cardiac remodelling, Heart failure, Left ventricular reverse remodelling, Non-ischaemic cardiomyopathy, Predictors, Reverse remodelling,
• MeSH
• echokardiografie MeSH
• funkce levé komory srdeční fyziologie   MeSH
• kardiomyopatie * MeSH
• lidé MeSH
• remodelace komor fyziologie   MeSH
• srdeční selhání * komplikace   etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH