Recent studies reported that a convolutional neural network (CNN; a deep learning model) can detect elevated pulmonary artery wedge pressure (PAWP) from chest radiographs, the diagnostic images most ...commonly used for assessing pulmonary congestion in heart failure. However, no method has been published for quantitatively estimating PAWP from such radiographs. We hypothesized that a regression CNN, an alternative type of deep learning, could be a useful tool for quantitatively estimating PAWP in cardiovascular diseases. We retrospectively enrolled 936 patients with cardiovascular diseases who had undergone right heart catheterization (RHC) and chest radiography and estimated PAWP by constructing a regression CNN based on the VGG16 model. We randomly categorized 80% of the data as training data (training group,
n
= 748) and 20% as test data (test group,
n
= 188). Moreover, we tuned the learning rate—one of the model parameters—by 5-hold cross-validation of the training group. Correlations between PAWP measured by RHC ground truth (GT) PAWP and PAWP derived from the regression CNN (estimated PAWP) were tested. To visualize how the regression CNN assessed the images, we created a regression activation map (RAM), a visualization technique for regression CNN. Estimated PAWP correlated significantly with GT PAWP in both the training (
r
= 0.76,
P
< 0.001) and test group (
r
= 0.62,
P
< 0.001). Bland–Altman plots found a mean (SEM) difference between GT and estimated PAWP of − 0.23 (0.16) mm Hg in the training and − 0.05 (0.41) mm Hg in the test group. The RAM showed that our regression CNN model estimated high PAWP by focusing on the cardiomegaly and pulmonary congestion. In the test group, the area under the curve (AUC) for detecting elevated PAWP (≥ 18 mm Hg) produced by the regression CNN model was similar to the AUC of an experienced cardiologist (0.86 vs 0.83, respectively;
P
= 0.24). This proof-of-concept study shows that regression CNN can quantitatively estimate PAWP from standard chest radiographs in cardiovascular diseases.
Aims: Smaller low-density lipoprotein (LDL) particle size has been suggested to result in the development of endothelial dysfunction, atherosclerosis, and in-stent restenosis (ISR); however, little ...is known regarding the impact of the LDL particle size on the neointima formation leading to ISR after everolimus-eluting stent (EES) implantation. Methods: In this study, we have included 100 patients to examine the relationship between an LDL-C/apolipoprotein B (Apo B) ≤ 1.2, reportedly representing the LDL particle size, and the neointimal characteristics using optical coherence tomography (OCT) and coronary angioscopy (CAS) during the follow-up coronary angiography (CAG) period (8.8±2.5 months) after EES implantation. We divided them into two groups: LDL-C/Apo B ≤ 1.2 group (low LDL-C/Apo B group, n=53) and LDL-C/Apo B >1.2 group (high LDL-C/Apo B group, n=47). Results: The low LDL-C/Apo B group had a significantly larger neointimal volume (12.8±5.3 vs. 10.3±4.9 mm3, p=0.021) and lower incidence of a neointimal homogeneous pattern (71 vs. 89 %), higher incidence of a neointimal heterogeneous pattern (25 vs. 9 %) (p=0.006) and higher prevalence of macrophage accumulation (9 vs. 2 %) (p=0.030) as assessed via OCT, and, as per the CAS findings, a higher prevalence of yellow grade ≥ 2 (grade 2; adjusted residual: 2.94, grade 3; adjusted residual: 2.00, p=0.017) than the high LDL-C/Apo B group. Conclusions: A low LDL-C/Apo B ratio was found to be strongly associated with neointimal proliferation and neointimal instability evidenced chronically by OCT and CAS. An LDL-C/Apo B ≤ 1.2 will be of aid in terms of identifying high-risk patients after EES implantation.
Substrate-induced gene expression (SIGEX) is a high-throughput promoter-trap method. It is a function-based metagenomic screening tool that relies on transcriptional activation of a reporter gene
(
) ...by a metagenomic DNA library upon induction with a substrate. However, its use is limited because of the relatively small size of metagenomic DNA libraries and incompatibility with screening metagenomes from anaerobic environments. In this study, these limitations of SIGEX were addressed by fine-tuning metagenome DNA library construction protocol and by using Evoglow, a green fluorescent protein that forms a chromophore even under anaerobic conditions. Two metagenomic libraries were constructed for subseafloor sediments offshore Shimokita Peninsula (Pacific Ocean) and offshore Joetsu (Japan Sea). The library construction protocol was improved by (a) eliminating short DNA fragments, (b) applying topoisomerase-based high-efficiency ligation, (c) optimizing insert DNA concentration, and (d) column-based DNA enrichment. This led to a successful construction of metagenome DNA libraries of approximately 6 Gbp for both samples. SIGEX screening using five aromatic compounds (benzoate, 3-chlorobenzoate, 3-hydroxybenzoate, phenol, and 2,4-dichlorophenol) under aerobic and anaerobic conditions revealed significant differences in the inducible clone ratios under these conditions. 3-Chlorobenzoate and 2,4-dichlorophenol led to a higher induction ratio than that for the other non-chlorinated aromatic compounds under both aerobic and anaerobic conditions. After the further screening of induced clones, a clone induced by 3-chlorobenzoate only under anaerobic conditions was isolated and characterized. The clone harbors a DNA insert that encodes putative open reading frames of unknown function. Previous aerobic SIGEX attempts succeeded in the isolation of gene fragments from anaerobes. This study demonstrated that some gene fragments require a strict
reducing environment to function and may be potentially missed when screened by aerobic induction. The newly developed anaerobic SIGEX scheme will facilitate functional exploration of metagenomes from the anaerobic biosphere.
Objective Sodium-glucose co-transporter-2 inhibitors (SGLT2is), such as dapagliflozin, have a diuretic effect, and their early initiation to treat acute heart failure (AHF) may improve outcomes; ...however, the significance of the timing of starting dapagliflozin after hospital admission remains unclear. Methods We performed a post hoc analysis of a prospective, observational registry. Participants were divided into the early (E) group and late (L) group using the median time to the initiation of dapagliflozin (6 days) as the cut-off. We evaluated the relationship between the time to the initiation of dapagliflozin after hospital admission and patient characteristics and the length of the hospital stay. Patients Study subjects were 118 patients with AHF admitted between January 2021 and April 2022 who were started on dapagliflozin treatment (10 mg/day). Results Patients were divided into the E group (n=63) and L group (n=55). The HF severity as evaluated by the New York Heart Association class and the N-terminal pro-brain natriuretic peptide level was not significantly different between the groups. The time to the initiation of dapagliflozin and length of hospital stay showed a significant positive correlation (p<0.001, r=0.46). The hospital stay was significantly shorter in group E median, 16.5 days; interquartile range (IQR): 13-22 days than in group L (median, 22 days; IQR: 17-27 days; p=0.002). A multivariate logistic regression analysis showed that the early initiation of dapagliflozin was independently associated with a shorter hospital stay, even after multiple adjustments. Conclusion Early initiation of dapagliflozin after hospital admission is associated with a shorter hospital stay, suggesting it is a key factor for shortening hospital stays.
The optimal timing for electrical cardioversion (ECV) in acute decompensated heart failure (ADHF) with atrial arrhythmias (AAs) is unknown. Here, we retrospectively evaluated the impact of ECV timing ...on SR maintenance, hospitalization duration, and cardiac function in patients with ADHF and AAs. Between October 2017 and December 2022, ECV was attempted in 73 patients (62 with atrial fibrillation and 11 with atrial flutter). Patients were classified into two groups based on the median number of days from hospitalization to ECV, as follows: early ECV (within 8 days,
n
= 38) and delayed ECV (9 days or more,
n
= 35). The primary endpoint was very short-term and short-term ECV failure (unsuccessful cardioversion and AA recurrence during hospitalization and within one month after ECV). Secondary endpoints included (1) acute ECV success, (2) ECVs attempted, (3) periprocedural complications, (4) transthoracic echocardiographic parameter changes within two months following successful ECV, and (5) hospitalization duration. ECV successfully restored SR in 62 of 73 patients (85%), with 10 (14%) requiring multiple ECV attempts (≥ 3), and periprocedural complications occurring in six (8%). Very short-term and short-term ECV failure occurred without between-group differences (51% vs. 63%,
P
= 0.87 and 61% vs. 72%,
P
= 0.43, respectively). Among 37 patients who underwent echocardiography before and after ECV success, the left ventricular ejection fraction (LVEF) significantly increased (38% 31–52 to 51% 39–63,
P
= 0.008) between admission and follow-up. Additionally, hospital stay length was shorter in the early ECV group than in the delayed ECV group (14 days 12–21 vs. 17 days 15–26,
P
< 0.001). Hospital stay duration was also correlated with days from admission to ECV (Spearman's
ρ
= 0.47,
P
< 0.001). In clinical practice, early ECV was associated with a shortened hospitalization duration and significantly increased LVEF in patients with ADHF and AAs.
Nonobstructive general angioscopy (NOGA) can identify vulnerable plaques in the aortic lumen that serve as potential risk factors for cardiovascular events such as embolism. However, the association ...between computed tomography (CT) images and vulnerable plaques detected on NOGA remains unknown.
We investigated 101 patients (67±11 years; women, 13.8%) who underwent NOGA and contrast-enhanced CT before or after 90 days in our hospital. On CT images, the aortic wall thickness, aortic wall area (AWA), and AWA in the vascular area were measured at the thickest point from the 6th to the 12th thoracic vertebral levels. Furthermore, the association between these measurements and the presence or absence of NOGA-derived aortic plaque ruptures (PRs) at the same vertebral level was assessed. NOGA detected aortic PRs in the aortic lumens at 145 (22.1%) of the 656 vertebral levels. The presence of PRs was significantly associated with greater aortic wall thickness (3.3±1.7 mm versus 2.1±1.2 mm), AWA (1.33±0.68 cm
versus 0.89±0.49 cm
), and AWA in the vascular area (23.2%±9.3% versus 17.2%±7.6%) (
<0.001 for all) on the CT scans compared with the absence of PRs. The frequency of PRs significantly increased as the aortic wall thickness increased. Notably, a few NOGA-derived PRs were detected on CT in near-normal intima.
The presence of NOGA-derived PRs was strongly associated with increased aortic wall thickness, AWA, and AWA in the vascular area, measured using CT. NOGA can detect PRs in the intima that appear almost normal on CT scans.
•Archaeal MutS1 has a mismatched DNA-recognition ability and an ATPase activity.•Archaeal MutL possesses a divalent metal ion-dependent nicking endonuclease activity.•MutS1 and MutL may be involved ...in DNA mismatch repair system in archaea.
In eukaryotes and most bacteria, the MutS1/MutL-dependent mismatch repair system (MMR) corrects DNA mismatches that arise as replication errors. MutS1 recognizes mismatched DNA and stimulates the nicking endonuclease activity of MutL to incise mismatch-containing DNA. In archaea, there has been no experimental evidence to support the existence of the MutS1/MutL-dependent MMR. Instead, it was revealed that a large part of archaea possess mismatch-specific endonuclease EndoMS, indicating that the EndoMS-dependent MMR is widely adopted in archaea. However, some archaeal genomes encode MutS1 and MutL homologs, and their molecular functions have not been revealed. In this study, we purified and characterized recombinant MutS1 and the C-terminal endonuclease domain of MutL from a methanogenic archaeon Methanosaeta thermophila (mtMutS1 and the mtMutL CTD, respectively). mtMutS1 bound to mismatched DNAs with a higher affinity than to perfectly-matched and other structured DNAs, which resembles the DNA-binding specificities of eukaryotic and bacterial MutS1 homologs. The mtMutL CTD showed a Mn2+/Ni2+/Co2+-dependent nicking endonuclease activity that introduces single-strand breaks into a circular double-stranded DNA. The nicking endonuclease activity of the mtMutL CTD was impaired by mutagenizing the metal-binding motif that is identical to those of eukaryotic and bacterial MutL endonucleases. These results raise the possibility that not only the EndoMS-dependent MMR but also the traditional MutS1/MutL-dependent MMR exist in archaea.
Background: Intra-Aortic Balloon Pump (IABP) has the potential to recover cardiogenic shock, blood flow to thecoronary arteries, or both; but bleeding events negatively affect the cardioprotective ...effects of IABP. Nonetheless,the real-world data in Japan regarding bleeding events after IABP implantation in patients with acute myocardialinfarction (AMI) remains insufficient.Methods: We investigated the incidence of major bleeding events in 249 AMI patients who underwent percutaneous coronary intervention (PCI) and IABP, with and without cardiogenic shock. In 97 (39%) patients, IABP wasused for cardiogenic shock, while 152 (61%) patients had IABP for other indications.Results: Patients with cardiogenic shock were significantly older and had a lower body weight, higher NT-proBNP and lactate levels, lower left ventricle ejection fraction (LVEF), and higher CREDO-Kyoto bleeding and PRECISE-DAPT scores than those without. During the follow-up period, 26 (10%) patients experienced a majorbleeding event, and 19 (8%) had major adverse cardiac events (MACE), but there were no significant differencesin those rates between those with and without cardiogenic shock. After multivariate analysis, anemia remained associated with a major bleeding event (adjusted odds ratio 2.40, 95% confidence interval 1.01–5.73, p = 0.047).Conclusions: Despite the low risk in patients who did not have cardiogenic shock, major bleeding events andMACE rates were similar to that of those with cardiogenic shock. Anemia was independently associated withmajor bleeding events in AMI patients who had IABP. The use of IABP should be carefully decided in AMI patients, especially in patients with noncardiogenic shock or anemia.
Background. The effect of left subclavian artery tortuosity during percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) remains unclear. Methods. Of 245 ACS ...patients (from November 2019 and May 2021), 79 who underwent PCI via a left radial approach (LRA) were included. We measured the angle of the left subclavian artery in the coronal view on CT imaging as an indicator of the tortuosity and investigated the association between that angle and the clinical variables and procedural time. Results. Patients with a left subclavian artery angle of a median of <70 degrees (severe tortuosity) were older (75.4 ± 11.7 vs. 62.9 ± 12.3 years, P<0.001) and had a higher prevalence of female sex (42.1% vs. 14.6%, P=0.007), hypertension (94.7% vs. 75.6%, P=0.02), and subclavian artery calcification (73.7% vs. 34.2%, P<0.001) than those with that ≥70 degrees. The left subclavian artery angle correlated negatively with the sheath cannulation to the first balloon time (ρ = −0.51, P<0.001) and total procedural time (ρ = −0.32, P=0.004). A multiple linear regression analysis revealed that the natural log transformation of the sheath insertion to first balloon time was associated with a subclavian artery angle of <70 degrees (β = 0.45, P<0.001). Conclusion. Our study showed that lower left subclavian artery angles as a marker of the tortuosity via the LRA were strongly associated with a longer sheath insertion to balloon time and subsequent entire procedure time during the PCI.