Optimal timing of electrical cardioversion for acute decompensated heart failure caused by atrial arrhythmias: The earlier, the better?

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.

Association Between Aortic Wall Parameters on Multidetector Computed Tomography and Ruptured Plaques By Nonobstructive General Angioscopy.

BACKGROUND: 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. METHODS AND RESULTS: 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 cm2 versus 0.89±0.49 cm2), and AWA in the vascular area (23.2%±9.3% versus 17.2%±7.6%) (P<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. CONCLUSIONS: 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.

Sodium-glucose co-transporter 2 inhibitors in acute heart failure: real-world prescription trends and outcomes analysis.

AIMS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown potential therapeutic benefits in heart failure (HF). However, data on their real-world usage and benefits in acute decompensated heart failure (ADHF) are limited. METHODS AND RESULTS: We conducted a post hoc analysis of real-world data from 1108 patients with ADHF admitted to Nihon University Itabashi Hospital (Tokyo, Japan) between 2018 and 2022. Patients were divided into two groups based on the prescription of SGLT2 inhibitors during hospitalization: an SGLT2 inhibitor group (SGLT2i group) (n = 289) and a non-SGLT2i group (n = 819). The primary endpoints were death and rehospitalization for HF after discharge. The median age was 76 [interquartile range (IQR): 66, 83] years, and 732 patients (66%) were male. Data showed an increasing trend in the prescription of SGLT2 inhibitors since 2021. During a median follow-up period of 366 days (IQR: 116, 614), 458 (41.3%) patients reached the primary endpoint. The Kaplan-Meier analysis showed that the SGLT2i group had a significantly lower rate of composite events than the non-SGLT2i group, both overall (log-rank test, P < 0.001) and in the following left ventricular ejection fraction (LVEF) subgroups: HF with reduced ejection fraction (EF) (n = 413), HF with mildly reduced EF (n = 226), and HF with preserved EF (n = 466) (log-rank test; P = 0.044, P = 0.013, and P = 0.001, respectively). Furthermore, patients starting SGLT2 inhibitors during hospitalization had a significantly lower rate of composite events than those not using SGLT2 inhibitors (log-rank test, P < 0.001). This association was also significant in the LVEF subgroups (P = 0.005, P = 0.032, and P = 0.004, respectively). CONCLUSIONS: The prescription and initiation of SGLT2 inhibitors during hospitalization are associated with improved post-discharge outcomes in patients with ADHF, irrespective of LVEF.

Association between aortic thrombi detected using non-obstructive general angioscopy and atrial fibrillation.

Atrial fibrillation (AF) is an independent risk factor for stroke and systemic embolism. Cardiogenic and aortogenic emboli are causes of stroke or systemic embolism. Non-obstructive general angioscopy (NOGA) can be used to diagnose aortic intimal findings, including thrombi and atherosclerotic plaques, but little is known about NOGA-derived aortic intimal findings in patients with AF. This study focused on aortic intimal findings in patients with AF and evaluated the association between AF and aortic thrombi detected using NOGA. We enrolled 283 consecutive patients with coronary artery disease who underwent NOGA of the aorta between January 2017 and August 2022. Aortic intimal findings were screened using NOGA after coronary arteriography. The patients were divided into two groups according to their AF history (AF, n = 50 and non-AF, n = 233). Patients in the AF group were older than those in the non-AF group. Sex, body mass index, and coronary risk factors were not significantly different between the two groups. In the NOGA findings, the presence of intense yellow plaques and ruptured plaques was not significantly different between the two groups. Aortic thrombi were more frequent in the AF group than in the non-AF group (92.0 vs. 71.6%, p < 0.001). Multivariate logistic regression found that AF was independently associated with aortic thrombi (odds ratio 3.87 [95% CI 1.28-11.6], p = 0.016). The presence of aortic thrombi observed using NOGA was associated with AF in patients with coronary artery disease. The roles of aortic thrombi as well as cardiogenic embolism may require clarification.

Impact of non-gated computed tomography on the timing of invasive strategy of patients with non-ST-elevation acute coronary syndrome.

Background: This study aimed to examine the clinical role of non-gated computed tomography (CT) in ruling out fatal chest pain in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS), with a focus on the time of arrival at the hospital to coronary angiography (CAG) and peak creatine kinase (CK) levels. Methods: We retrospectively examined 196 NSTE-ACS patients who were admitted with urgently diagnosed NSTE-ACS and underwent percutaneous coronary intervention between March 2019 and October 2022. The patients were divided into three groups, namely, non-CT group, CT and defect- group, and CT and defect+ group, based on whether they underwent a CT scan and the presence or absence of perfusion defects on the CT image. Results: After the initial admission for NSTE-ACS, 40 patients (20.4%) underwent non-gated CT prior to CAG. Among these 40 patients, 27 had a perfusion defect on the CT scan. The incidence of contrast-induced nephropathy was not different among the three groups. The CT and defect+ group had a shorter arrival-to-CAG time than that of the non-CT group. In NSTE-ACS patients with elevated CK levels, the CT and defect+ group had lower peak CK levels than those in the non-CT group. Conclusion: NSTE-ACS patients with perfusion defects on non-gated CT had a shorter time from arrival to CAG, which might be associated with a lower peak CK. Non-gated CT might be useful for early diagnosis and early revascularization in the clinical setting of NSTE-ACS.

Early Initiation of Dapagliflozin during Hospitalization for Acute Heart Failure Is Associated with a Shorter Hospital Stay.

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.

Prognostic significance of pulmonary arterial wedge pressure estimated by deep learning in acute heart failure.

AIMS: Acute decompensated heart failure (ADHF) presents with pulmonary congestion, which is caused by an increased pulmonary arterial wedge pressure (PAWP). PAWP is strongly associated with prognosis, but its quantitative evaluation is often difficult. Our prior work demonstrated that a deep learning approach based on chest radiographs can calculate estimated PAWP (ePAWP) in patients with cardiovascular disease. Therefore, the present study aimed to assess the prognostic value of ePAWP and compare it with other indices of haemodynamic congestion. METHODS AND RESULTS: We conducted a post hoc analysis of a single-centre, prospective, observational heart failure registry and analysed data from 534 patients admitted for ADHF between January 2018 and December 2019. The deep learning approach was used to calculate ePAWP from chest radiographs at admission and discharge. Patients were divided into three groups based on the ePAWP tertiles at discharge, as follows: first tertile group (ePAWP ≤ 11.2 mm Hg, n = 178), second tertile group (11.2 < ePAWP < 13.5 mm Hg, n = 170), and third tertile group (ePAWP ≥ 13.5 mm Hg, n = 186). The third tertile group had a higher prevalence of atrial fibrillation and lower systolic blood pressure at admission; a lower platelet count and higher total bilirubin at both admission and discharge; and a higher left atrial diameter, peak early diastolic transmitral flow velocity, right ventricular end-diastolic diameter, and maximal inferior vena cava diameter at discharge. During the median follow-up period of 289 days, 223 (41.7%) patients reached the primary endpoint (a composite of all-cause mortality or rehospitalization for heart failure). Kaplan-Meier analysis revealed a significantly higher composite event rate in the third tertile group (log-rank test, P = 0.006). Even when adjusted for clinically relevant factors, a higher ePAWP at discharge and a smaller decrease in ePAWP from admission to discharge were significantly associated with higher event rates [ePAWP at discharge: hazard ratio, 1.10; 95% confidence interval (CI), 1.02-1.19; P = 0.010; and size of ePAWP decrease: hazard ratio, 0.94; 95% CI, 0.89-0.99; P = 0.038]. CONCLUSIONS: Our study suggests that ePAWP calculated by a deep learning approach may be useful for identifying and monitoring pulmonary congestion during hospitalization for ADHF.

Association between the Angle of the Left Subclavian Artery and Procedural Time for Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome.

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 (ß = 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.

Prognostic importance of improving hepatorenal function during hospitalization in acute decompensated heart failure.

AIMS: The Model for End-stage Liver Disease eXcluding International normalized ratio (MELD-XI) is an established scoring system that reflects hepatorenal function. However, little is known about the prognostic value of changes in MELD-XI score during hospitalization in acute decompensated heart failure (ADHF). METHODS AND RESULTS: We prospectively analysed 536 patients admitted for ADHF between January 2018 and December 2019. In the MELD-XI, 9.44 is the lowest possible score and considered to be normal, and values above 9.44 are classified as high. We calculated MELD-XI scores at admission and discharge and used them to divide patients into four groups depending on whether the score was high (>9.44) or normal (9.44) at each time point as follows: normal score at both measurements (persistently normal group, n = 99), high score at admission and normal score at discharge (high-to-normal group, n = 108), normal score at admission and high score at discharge (normal-to-high group, n = 24), and high score at both measurements (persistently high group, n = 305). The persistently high group had higher blood urea nitrogen, creatinine, and N-terminal pro-brain natriuretic peptide levels at both admission and discharge and significantly higher left ventricular end-diastolic, left atrial, right ventricular end-diastolic, and maximal inferior vena cava diameters at discharge. During the median follow-up period of 369 days (Q1, Q3: 97, 576), 231 (43.1%) patients reached the primary endpoint (a composite of all-cause death or re-hospitalization for heart failure). The Kaplan-Meier analysis revealed a significantly higher composite event rate in the persistently high group than in the persistently normal and high-to-normal groups (log-rank test, P < 0.001). Compared with the persistently high group, the high-to-normal group remained significantly associated with lower composite event risk after multivariate adjustment (hazard ratio, 0.30; 95% CI, 0.12-0.69; P = 0.004). CONCLUSIONS: Our study suggests that changes in hepatorenal function during hospitalization are associated with the severity of heart failure and systemic congestion and that they provide useful information for predicting clinical outcomes in patients with ADHF.

Quantitative estimation of pulmonary artery wedge pressure from chest radiographs by a regression convolutional neural network.

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.

Clinical Importance of the LDL-C/Apolipoprotein B Ratio for Neointimal Formation after Everolimus-Eluting Stent Implantations.

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.

Absence of coronary angioscopy-derived in-stent thrombi is associated with major bleeding events in acute myocardial infarction.

BACKGROUND AND AIMS: The optimal duration of dual antiplatelet therapy for acute myocardial infarction is controversial because the bleeding risk outweighs the thromboembolic risk. We hypothesized that an in-stent thrombus (IS-thrombus) detected by coronary angioscopy (CAS) after stent implantation would be associated with high bleeding risk. METHODS: This study included 208 patients who underwent CAS at 2 weeks after stent implantation for an acute myocardial infarction. The study was approved by the ethics committee at the Nihon University Itabashi Hospital (reference number RK-200714-10). RESULTS: In 84 patients, in whom no IS-thrombus was identified in the culprit vessel using CAS, the major bleeding event rate was significantly higher than that in patients with IS-thrombi (n = 124). However, no difference was detected in major adverse cardiovascular events (MACE; stroke, hospitalization for a non-fatal myocardial infarction/unstable angina, target lesion revascularization, and cardiovascular death). After adjustments by the propensity score based on patient characteristics, the absence of IS-thrombi remained an independent predictor of major bleeding events (hazard ratio 4.73, 95% confidence interval 2.04-11.00, p < 0.001). CONCLUSIONS: The absence of CAS-detected IS-thrombi in the subacute phase was independently associated with future major bleeding events, but not with MACE. These findings may help optimize the duration of dual antiplatelet therapy.

Construction of Aerobic/Anaerobic-Substrate-Induced Gene Expression Procedure for Exploration of Metagenomes From Subseafloor Sediments.

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 green fluorescence protein (gfp) 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 in vivo 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.

Biochemical characterization of mismatch-binding protein MutS1 and nicking endonuclease MutL from a euryarchaeon Methanosaeta thermophila.

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.