International heart journal最新文献

This study aimed to clarify (1) the association among the atrial fibrillation (AF) type, sleep-disordered breathing (SDB), heart failure (HF), and left atrial (LA) enlargement, (2) the independent predictors of LA enlargement, and (3) the effects of ablation on those conditions in patients with AF. The study's endpoint was LA enlargement (LA volume index [LAVI] ≥ 78 mL/m²).

Of 423 patients with nonvalvular AF, 236 were enrolled. We evaluated the role of the clinical parameters such as the AF type, SDB severity, and HF in LA enlargement. Among them, 141 patients exhibiting a 3% oxygen desaturation index (ODI) of ≥ 10 events/hour underwent polysomnography to evaluate the SDB severity measured by the apnea-hypopnea index (AHI). The LA enlargement and HF were characterized by the LA diameter/LAVI, an increase in the B-type natriuretic peptide level, and a lower left ventricular ejection fraction.

This study showed that non-paroxysmal AF (NPAF) rather than paroxysmal AF (PAF), the SDB severity, LA enlargement, and HF progression had bidirectional associations and exacerbated each other, which generated a vicious cycle that contributed to the LA enlargement. NPAF (OR = 4.55, P < 0.001), an AHI of ≥ 25.10 events/hour (OR = 1.55, P = 0.003), and a 3% ODI of ≥ 15.43 events/hour (OR = 1.52, P = 0.003) were independent predictors of an acceleration of the LA enlargement. AF ablation improved the HF and LA enlargement.

To break this vicious cycle, AF ablation may be the basis for suppressing the LA enlargement and HF progression subsequently eliminating the substrates for AF and SDB in patients with AF.

Hydrogen sulfide (H₂S) has been identified as a novel gasotransmitter and a substantial antioxidant that can activate various cellular targets to regulate physiological and pathological processes in mammals. However, under physiological conditions, it remains unclear whether it is involved in regulating cardiomyocyte (CM) proliferation during postnatal development in mice. This study mainly aimed to evaluate the role of H₂S in postnatal CM proliferation and its regulating molecular mechanisms. We found that sodium hydrosulfide (NaHS, the most widely used H₂S donor, 50-200 μM) increased neonatal mouse primary CM proliferation in a dose-dependent manner in vitro. Consistently, exogenous administration of H₂S also promoted CM proliferation and increased the total number of CMs at postnatal 7 and 14 days in vivo. Moreover, we observed that the protein expression of SIRT1 was significantly upregulated after NaHS treatment. Inhibition of SIRT1 with EX-527 or si-SIRT1 decreased CM proliferation, while enhancement of the activation of SIRT1 with SRT1720 promoted CM proliferation. Meanwhile, pharmacological and genetic blocking of SIRT1 repressed the effect of NaHS on CM proliferation. Taken together, these results reveal that H₂S plays a promotional role in proliferation of CMs in vivo and in vitro and SIRT1 is required for H₂S-mediated CM proliferation, which indicates that H₂S may be a potential modulator for heart development in postnatal time window.

Late kidney injury (LKI) in patients with acute heart failure (AHF) requiring intensive care is poorly understood.

We analyzed 821 patients with AHF who required intensive care. We defined LKI based on the ratio of the creatinine level 1 year after admission for AHF to the baseline creatinine level. The patients were categorized into 4 groups based on this ratio: no-LKI (< 1.5, n = 509), Class R (risk; ≥ 1.5, n = 214), Class I (injury; ≥ 2.0, n = 78), and Class F (failure; ≥ 3.0, n = 20). Median follow-up after admission for AHF was 385 (346-426) days. Multivariate logistic regression analysis revealed that acute kidney injury (AKI) during hospitalization (Class R, odds ratio [OR]: 1.710, 95% confidence interval [CI]: 1.138-2.571, P = 0.010; Class I, OR: 6.744, 95% CI: 3.739-12.163, P < 0.001; and Class F, OR: 9.259, 95% CI: 4.078-18.400, P < 0.001) was independently associated with LKI. Multivariate Cox regression analysis showed that LKI was an independent predictor of 3-year all-cause death after final follow-up (hazard ratio: 1.545, 95% CI: 1.099-2.172, P = 0.012). The rate of all-cause death was significantly lower in the no-AKI/no-LKI group than in the no-AKI/LKI group (P = 0.048) and in the AKI/no-LKI group than in the AKI/LKI group (P = 0.017).

The incidence of LKI was influenced by the presence of AKI during hospitalization, and was associated with poor outcomes within 3 years of final follow-up. In the absence of LKI, AKI during hospitalization for AHF was not associated with a poor outcome.

Periodontitis is a common chronic infection and is associated with cardiovascular disease. This study evaluated whether basic oral care for periodontal disease could improve endothelial function in patients with acute coronary syndrome (ACS).

This study enrolled 54 patients with acute coronary syndrome admitted to Kagoshima City Hospital and who had undergone percutaneous coronary intervention. Flow-mediated endothelium-dependent dilatation (FMD) was measured before discharge (initial FMD) and at 8 months after percutaneous coronary intervention (follow-up FMD). The following periodontal characteristics were measured: periodontal pocket depth (PPD, mm), plaque control record (%), and bleeding on probing (%). All patients received basic oral care instructions from dentists. The oral health condition was generally poor in the participants and there were 24 patients (44.4%) who had severe PPD. Despite the intervention of basic oral care, the periodontal characteristics did not improve during the study period; initial FMD and follow-up FMD did not significantly differ (4.38 ± 2.74% versus 4.56 ± 2.51%, P = 0.562). However, the follow-up FMD was significantly lower in patients with severe PPD (≥ 6.0 mm, n = 24) than in patients without severe PPD (≤ 5.0 mm, n = 30) (FMD: 3.58 ± 1.91% versus 5.37 ± 2.67%, P = 0.007). FMD tended to be worse in patients with severe PPD than in patients without severe PPD (ΔFMD: -0.55 ± 2.12 versus 0.81 ± 2.77 %, P = 0.055). In conclusion, during the use of basic oral care, endothelial function improved in patients without severe PPD, while it worsened in patients with severe PPD.

The impact of tolvaptan and low-dose dopamine on heart failure (HF) patients with acute kidney injury (AKI) remains uncertain from a clinical standpoint.

HF patients with AKI were selected and divided in a 1:1 fashion into the dopamine combined with the tolvaptan group (DTG), the tolvaptan group (TG), and the control group (CG). According to the standard of care, TG received tolvaptan 15 mg orally daily for a week. DTG received combination treatment, including 7 consecutive days of dopamine infusion (2 μg/kg・minutes) and oral tolvaptan 15 mg. Venous blood and urine samples were taken before and after therapy. The primary endpoint was the cardiorenal serological index after 7 days of treatment.

Sixty-five patients were chosen randomly for the DTG (22 patients), TG (20 patients), and CG (23 patients), which were similar before the treatment. The serum indexes related to cardiac function (N-terminal probrain natriuretic peptide and cardiac troponin I) in DTG were decreased, compared with TG and CG (P < 0.05). Furthermore, the serological markers of renal function (serum cystatin C, serum creatinine, and neutrophil gelatinase-associated lipocalin) in DTG were lower than those in TG and CG (P < 0.05). There was no significant difference in the incidence of adverse reactions among groups.

Low-dose dopamine combined with tolvaptan can markedly improve patients' cardiac and renal function. This may be considered a new therapeutic method for HF patients with AKI.

This study aimed to investigate the molecular mechanisms underlying the protective effects of cyclooxygenase (cox) inhibitors against myocardial hypertrophy.

Rat H9c2 cardiomyocytes were induced by mechanical stretching. SD rats underwent transverse aortic constriction to induce pressure overload myocardial hypertrophy. Rats were subjected to echocardiography and tail arterial pressure in 12W. qPCR and western blot were used to detect the expression of Notch-related signaling. The inflammatory factors were tested by ELISA in serum, heart tissue, and cell culture supernatant.

Compared with control, levels of pro-inflammatory cytokines IL-6, TNF-α, and IL-1β were increased and anti-inflammatory cytokine IL-10 was reduced in myocardial tissues and serum of rat models. Levels of Notch1 and Hes1 were reduced in myocardial tissues. However, cox inhibitor treatment (aspirin and celecoxib), the improvement of exacerbated myocardial hypertrophy, fibrosis, dysfunction, and inflammation was parallel to the activation of Notch1/Hes1 pathway. Moreover, in vitro experiments showed that, in cardiomyocyte H9c2 cells, application of ~20% mechanical stretching activated inflammatory mediators (IL-6, TNF-α, and IL-1β) and hypertrophic markers (ANP and BNP). Moreover, expression levels of Notch1 and Hes1 were decreased. These changes were effectively alleviated by aspirin and celecoxib.

Cox inhibitors may protect heart from hypertrophy and inflammation possibly via the Notch1/Hes1 signaling pathway.

This study aimed to explore the expression of long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in patients with acute myocardial infarction (AMI) and its inflammatory regulation mechanism through miR-211/interleukin 10 (IL-10) axis.

A total of 75 participants were enrolled in this study: 25 healthy people in the control group, 25 patients with stable angina pectoris (SAP) in the SAP group, and 25 patients with AMI in the AMI group. Real-time qPCR was used to detect mRNA expression levels of NEAT1, miR-211, and IL-10. The interaction between miR-211, NEAT1, and IL-10 was confirmed by dual-luciferase reporter assay, and protein expression was detected using western blot.

High expression of NEAT1 in peripheral blood mononuclear cells (PBMCs) of patients with AMI was negatively related to serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), IL-6, and IL-1β and was positively correlated with left ventricular ejection fraction (LVEF). In THP-1 cells, miR-211 was confirmed to target and inhibit IL-10 expression. NEAT1 knockdown and miR-211-mimic markedly decreased IL-10 protein levels, whereas anti-miR-211 markedly increased IL-10 protein levels. Importantly, miR-211 level was negatively related to NEAT1 and IL-10 levels, whereas IL-10 level was positively related to the level of NEAT1 expression in PBMCs of patients with AMI.

LncRNA NEAT1 was highly expressed in PBMCs of patients with AMI, and NEAT1 suppressed inflammation via miR-211/IL-10 axis in PBMCs of patients with AMI.

Cardiac ryanodine receptor (RyR2) gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Conversely, RyR2 loss-of-function mutations cause a new disease entity, termed calcium release deficiency syndrome (CRDS), which may include RYR2-related long QT syndrome (LQTS). Importantly, unlike CPVT, patients with CRDS do not always exhibit exercise- or epinephrine-induced ventricular arrhythmias, which precludes a diagnosis of CRDS. Here we report a boy and his father, who both experienced exercise-induced cardiac events and harbor the same RYR2 E4107A variant. In the boy, an exercise stress test (EST) and epinephrine provocation test (EPT) did not induce any ventricular arrhythmias. QTc was slightly prolonged (QTc: 474 ms), and an EPT induced QTc prolongation (QTc-baseline: 466 ms, peak: 532 ms, steady-state: 527 ms). In contrast, in his father, QTc was not prolonged (QTc: 417 ms), and neither an EST nor EPT induced QTc prolongation. However, an EST induced multifocal premature ventricular contraction (PVC) bigeminy and bidirectional PVC couplets. Thus, they exhibited distinct clinical phenotypes: the boy exhibited LQTS (or CRDS) phenotype, whereas his father exhibited CPVT phenotype. These findings suggest that, in addition to the altered RyR2 function, other unidentified factors, such as other genetic, epigenetic, and environmental factors, and aging, may be involved in the diverse phenotypic manifestations. Considering that a single RYR2 variant can cause both CPVT and LQTS (or CRDS) phenotypes, in cascade screening of patients with CPVT and CRDS, an EST and EPT are not sufficient and genetic analysis is required to identify individuals who are at increased risk for life-threatening arrhythmias.

Cardiomyocyte hypertrophy plays a crucial role in heart failure development, potentially leading to sudden cardiac arrest and death. Previous studies suggest that micro-ribonucleic acids (miRNAs) show promise for the early diagnosis and treatment of cardiomyocyte hypertrophy.

To investigate the miR-378 expression in the cardiomyocyte hypertrophy model, reverse transcription-polymerase chain reaction (RT-qPCR), Western blot, and immunofluorescence tests were conducted in angiotensin II (Ang II)-induced H9c2 cells and Ang II-induced mouse model of cardiomyocyte hypertrophy. The functional interaction between miR-378 and AKT2 was studied by dual-luciferase reporter, RNA pull-down, Western blot, and RT-qPCR assays.

The results of RT-qPCR analysis showed the downregulated expression of miR-378 in both the cell and animal models of cardiomyocyte hypertrophy. It was observed that the introduction of the miR-378 mimic inhibited the hypertrophy of cardiomyocytes induced by Ang II. Furthermore, the co-transfection of AKT2 expression vector partially mitigated the negative impact of miR-378 overexpression on Ang II-induced cardiomyocytes. Molecular investigations provided evidence that miR-378 negatively regulated AKT2 expression by interacting with the 3' untranslated region (UTR) of AKT2 mRNA.

Decreased miR-378 expression and AKT2 activation are linked to Ang II-induced cardiomyocyte hypertrophy. Targeting miR-378/AKT2 axis offers therapeutic opportunity to alleviate cardiomyocyte hypertrophy.

Cholesterol crystal (CC) embolism is a disease in which CCs from atherosclerotic lesions embolize peripheral arteries, causing organ dysfunction. In this case, a patient with spontaneously ruptured aortic plaques (SRAPs) identified by non-obstructive general angioscopy (NOGA) may have developed a CC embolism. This is the first report of a CC embolism in a patient with SRAPs identified using NOGA, which further supports the previously speculated pathogenesis of CC embolism due to SRAPs.