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Constipation has been reported to increase the risk of cardiovascular mortality. Patients with atrial fibrillation (AF) and heart failure (HF) have more comorbidities and an increased bleeding risk. However, it remains unclear whether constipation is associated with an increased risk of incident bleeding complications in AF with HF. Here, we investigated the association between constipation requiring laxatives and major bleeding in AF and HF. We retrospectively analyzed the medical records of 370 consecutive patients hospitalized for AF and congestive HF. Constipation was defined as regularly taking laxatives or having at least two prescriptions for a ≥ 30-day supply of laxatives. Sixty patients experienced major bleeding events during a median follow-up of 318 days. The most common sites of bleeding were lower gastrointestinal (28%, 17/60), upper gastrointestinal (27%, 16/60), and intracranial (20%, 12/60). There were 33 (55%) patients with constipation in the bleeding group and 107 (35%) in the non-bleeding group (P = 0.004). Multivariate Cox regression analysis adjusted for HAS-BLED score, hemoglobin, and direct oral anticoagulant use showed that constipation (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.11–3.08; p = 0.019) was a significant risk factor for major bleeding. We found a significant association between constipation requiring laxatives and major bleeding in patients with AF and HF. These findings indicate the need for constipation prevention in these patients to avoid reliance on invasive defecation management, including laxatives.

This prospective study was conducted according to the principles outlined within the Declaration of Helsinki, and approved by the Ethics Review Board of National Center for Global Health and Medicine (NCGM-G-00839-01, NCGM-G-00839-02).

This study was to investigate the significance of 11C-Pittsburgh B (PIB) PET/CT in patients with suspected cardiac amyloidosis compared with 99mTc-aprotinin scintigraphy. Thirteen consecutive patients with suspected cardiac amyloidosis were considered for enrolment in this prospective pilot study. Participants were scheduled to undergo a series of 11C-PIB PET/CT and 99mTc-aprotinin within a 2-month period. Finally, we evaluated nine cases who underwent both imaging modalities, and compared imaging results with clinical and pathological results and prognosis. Six of the 9 patients who underwent both imaging modalities were diagnosed with amyloidosis, of whom 3 patients were diagnosed with cardiac amyloidosis from endomyocardial biopsy. These 3 patients with positive 11C-PIB uptake at the left ventricle wall showed worsening of cardiac function progressing in the short term or death caused by acute exacerbation of chronic heart failure. Six of 8 patients with positive uptake on 99mTc-aprotinin presented with amyloid deposition in the left ventricle wall, but symptoms remained stable if results of 11C-PIB were not positive. In a small sample of subjects, the present study showed that 11C-PIB accumulation in myocardium indicated cardiac amyloidosis with poor prognosis. Uptake of 11C-PIB may be related to progressive amyloid deposition to the heart and can predict patient prognosis.

The cardiac homeobox protein Nkx2-5 is essential in cardiac development, and mutations in Csx (which encodes Nkx2-5) cause various congenital heart diseases. Using the yeast two-hybrid system with Nkx2-5 as the 'bait', we isolated the T-box-containing transcription factor Tbx5; mutations in TBX5 cause heart and limb malformations in Holt-Oram syndrome (HOS). Co-transfection of Nkx2-5 and Tbx5 into COS-7 cells showed that they also associate with each other in mammalian cells. Glutathione S-transferase (GST) 'pull-down' assays indicated that the N-terminal domain and N-terminal part of the T-box of Tbx5 and the homeodomain of Nkx2-5 were necessary for their interaction. Tbx5 and Nkx2-5 directly bound to the promoter of the gene for cardiac-specific natriuretic peptide precursor type A (Nppa) in tandem, and both transcription factors showed synergistic activation. Deletion analysis showed that both the N-terminal domain and T-box of Tbx5 were important for this transactivation. A G80R mutation of Tbx5, which causes substantial cardiac defects with minor skeletal abnormalities in HOS, did not activate Nppa or show synergistic activation, whereas R237Q, which causes upper-limb malformations without cardiac abnormalities, activated the Nppa promoter to a similar extent to that of wildtype Tbx5. P19CL6 cell lines overexpressing wildtype Tbx5 started to beat earlier and expressed cardiac-specific genes more abundantly than did parental P19CL6 cells, whereas cell lines expressing the G80R mutant did not differentiate into beating cardiomyocytes. These results indicate that two different types of cardiac transcription factors synergistically induce cardiac development.