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BackgroundNatural history of atrial and ventricular secondary mitral regurgitation (SMR) is poorly understood. We compared the impact of the degree of SMR on survival between atrial and ventricular dysfunction.MethodsWe conducted a retrospective cohort study of patients who underwent echocardiography in a healthcare network between 2013-2018. We compared the survival of patients with atrial and ventricular dysfunction, using propensity scores developed from differences in patient demographics and comorbidities within SMR severity strata (none, mild, moderate or severe). We fitted Cox proportional hazards models to estimate the risk-adjusted hazards of death across different severities of SMR between patients with atrial and ventricular dysfunction.ResultsOf 11,987 patients included (median age 69 years [IQR 58-80]; 46% women), 6,254 (52%) had isolated atrial dysfunction, and 5,733 (48%) had ventricular dysfunction. 3,522 patients were matched from each arm using coarsened exact matching. Hazard of death in atrial dysfunction without SMR was comparable to ventricular dysfunction without SMR (HR 1.1, 95% CI 0.9-1.3). Using ventricular dysfunction without SMR as reference, hazards of death remained higher in ventricular dysfunction than in atrial dysfunction across increasing severities of SMR: mild SMR (HR 2.1, 95% CI 1.8-2.4 in ventricular dysfunction versus HR 1.7, 95%CI 1.5-2.0 in atrial dysfunction) and moderate/severe SMR (HR 2.8, 95%CI 2.4-3.4 versus HR 2.4, 95%CI 2.0-2.9).ConclusionsSMR across all severities were associated with better survival in atrial dysfunction than in ventricular dysfunction, though the magnitude of the diminishing survival were similar between atrial and ventricular dysfunction in increasing severity of SMRs.

BackgroundPatients with restrictive or hypertrophic cardiomyopathy (RCM/HCM) and congenital heart disease (CHD) do not derive clinical benefit from inotropes and mechanical circulatory support. Concerns were expressed that the new heart allocation system implemented in October 2018 would disadvantage these patients. This paper aimed to examine the impact of the new adult heart allocation system on transplantation and outcomes among patients with RCM/HCM/CHD.MethodsWe identified adult patients with RCM/HCM/CHD in the United Network for Organ Sharing (UNOS) database who were listed for or received a cardiac transplant from April 2017-June 2020. The cohort was separated into those listed before and after allocation system changes. Demographics and recipient characteristics, donor characteristics, waitlist survival, and post-transplantation outcomes were analyzed.ResultsThe number of patients listed for RCM/HCM/CHD increased after the allocation system change from 429 to 517. Prior to the change, the majority RCM/HCM/CHD patients were Status 1A at time of transplantation; afterwards, most were Status 2. Wait times decreased significantly for all: RCM (41 days vs 27 days; PConclusionsThe new allocation system has had a positive impact on time to transplantation of patients with RCM, HCM, and CHD without negatively influencing survival.

ImportancePatient outcomes in heart failure clinical trials are generally better than those observed in real-world settings. This may be related to stricter inclusion and exclusion criteria in clinical trials.ObjectiveWe study sought to characterize the clinical implications of differences between patients in clinical trials and those in a real-world registry of patients receiving left ventricular assist devices (LVADs).Design, setting, and participantsThis retrospective cohort study included all patients in INTERMACS (the Interagency Registry for Mechanically Assisted Circulatory Support) who were implanted with an axial flow LVAD from 2010 to 2015 to allow for equivalent comparisons.Main outcomes and measuresDifferences in patient characteristics and 2-year rates of adverse outcomes with those reported in the ENDURANCE and MOMENTUM 3 clinical trials. Survival analyses were used to assess the relationships between prespecified patient factors and clinical outcomes.ResultsOf the 10,937 LVAD recipients identified in INTERMACS between 2010-2015, 44% met at least 1 clinical trial exclusion criterion. The 2-year incidence of stroke and death amongst LVAD recipients in INTERMACS and the landmark clinical trials differed significantly (PConclusions and relevanceMost exclusion criteria used in LVAD clinical trials did not afford a substantially greater risk to patients in the real-world setting. In the relatively infrequent cases of end stage renal disease, thrombocytopenia, respiratory failure, and need for ECMO, the risks and benefits of LVAD therapy need careful weighting and further study.

Recent studies suggest that action video game players exhibit superior performance in visuospatial cognitive tasks compared with non-game players. However, the neural basis underlying this visuospatial cognitive performance advantage remains largely unknown. The present human behavioral and imaging study compared gray matter volume in action video game experts and non-experts using structural magnetic resonance imaging and voxel-based morphometry analysis. The results revealed significantly larger gray matter volume in the right posterior parietal cortex in experts compared with non-experts. Furthermore, the larger gray matter volume in the right posterior parietal cortex significantly correlated with individual performance in a visual working memory task in experts. These results suggest that differences in brain structure may be linked to extensive video game play, leading to superior visuospatial cognitive performance in action video game experts.

Mycobacterium avium complex (MAC) causes mainly two types of disease. The first is disseminated disease in immunocompromised hosts, such as individuals infected by human immunodeficiency virus (HIV). The second is pulmonary disease in individuals without systemic immunosuppression, and the incidence of this type is increasing worldwide. M. avium subsp. hominissuis, a component of MAC, causes infection in pigs as well as in humans. Many aspects of the different modes of M. avium infection and its host specificity remain unclear. Here, we report the characteristics and complete sequence of a novel plasmid, designated pMAH135, derived from M. avium strain TH135 in an HIV-negative patient with pulmonary MAC disease. The pMAH135 plasmid consists of 194,711 nucleotides with an average G + C content of 66.5% and encodes 164 coding sequences (CDSs). This plasmid was unique in terms of its homology to other mycobacterial plasmids. Interestingly, it contains CDSs with sequence homology to mycobactin biosynthesis proteins and type VII secretion system-related proteins, which are involved in the pathogenicity of mycobacteria. It also contains putative conserved domains of the multidrug efflux transporter. Screening of isolates from humans and pigs for genes located on pMAH135 revealed that the detection rate of these genes was higher in clinical isolates from pulmonary MAC disease patients than in those from HIV-positive patients, whereas the genes were almost entirely absent in isolates from pigs. Moreover, variable number tandem repeats typing analysis showed that isolates carrying pMAH135 genes are grouped in a specific cluster. Collectively, the pMAH135 plasmid contains genes associated with M. avium's pathogenicity and resistance to antimicrobial agents. The results of this study suggest that pMAH135 influence not only the pathological manifestations of MAC disease, but also the host specificity of MAC infection.

Mycobacterium avium complex (MAC) infection causes disseminated disease in immunocompromised hosts, such as human immunodeficiency virus (HIV)-positive patients, and pulmonary disease in persons without systemic immunosuppression, which has been increasing in many countries. In Japan, the incidence of pulmonary MAC disease caused by M. avium is about 7 times higher than that caused by M. intracellulare. To explore the bacterial factors that affect the pathological state of MAC disease caused by M. avium, we determined the complete genome sequence of the previously unreported M. avium subsp. hominissuis strain TH135 isolated from a HIV-negative patient with pulmonary MAC disease and compared it with the known genomic sequence of M. avium strain 104 derived from an acquired immunodeficiency syndrome patient with MAC disease. The genome of strain TH135 consists of a 4,951,217-bp circular chromosome with 4,636 coding sequences. Comparative analysis revealed that 4,012 genes are shared between the two strains, and strains TH135 and 104 have 624 and 1,108 unique genes, respectively. Many strain-specific regions including virulence-associated genes were found in genomes of both strains, and except for some regions, the G+C content in the specific regions was low compared with the mean G+C content of the corresponding chromosome. Screening of clinical isolates for genes located in the strain-specific regions revealed that the detection rates of strain TH135-specific genes were relatively high in specimens isolated from pulmonary MAC disease patients, while, those of strain 104-specific genes were relatively high in those from HIV-positive patients. Collectively, M. avium strains that cause pulmonary and disseminated disease possess genetically distinct features, and it suggests that the acquisition of specific genes during strain evolution has played an important role in the pathological manifestations of MAC disease.