Pulsatile tinnitus (PT) is a symptom consisting of the perception of sound without an external stimulus, synchronized with the patient's heartbeat.It accounts for 4% of all tinnitus cases. The most common etiologies are vascular, including carotid stenosis, idiopathic intracranial hypertension, sinus stenosis, aneurysms, and arteriovenous malformations. The diagnostic approach involves a complete history and clinical examination to determine if PT is of arterial or venous origin and to guide imaging studies. Treatment ranges from lifestyle modifications and pharmacological therapy to minimally invasive procedures like endovascular interventions and surgery. Minimally invasive endovascular procedures offer promising outcomes. This narrative review analyzes the etiologies, diagnostic approaches, and management strategies of PT, providing updated information to guide its approach. Most patients with PT have a treatable cause; however, despite a thorough diagnostic approach, a specific etiology is not found in approximately 30% of cases. Although most etiologies of PT are not life-threatening, it affects the patient's quality of life as it provokes psychological disturbances.

Changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels may not fully translate into patient-reported health status in patients with heart failure (HF). We aimed to evaluate the correlation between NT-proBNP levels and patient-reported health status changes at one month after discharge of patients, and their associations with risk of death and rehospitalization in patients with acute HF.

We used data from the China Patient-centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (PEACE 5p-HF Study). Patient-reported health status was measured by the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Patients who were hospitalized for HF and completed the KCCQ-12 and NT-proBNP tests before and one month after discharge were eligible in our study. We stratified patients into change groups based on NT-proBNP levels (i.e., improved, stable, and deteriorated) and KCCQ-12 scores (i.e., not deteriorated and deteriorated). We also examined the associations of the joint NT-proBNP and KCCQ-12 change with the risk of one-year and four-year clinical outcomes.

A total of 2461 patients were included in the analysis. The mean age was 64.06 ± 13.51 years, and 36.37% (895/2461) of the study population were female. Among patients with improved NT-proBNP levels, 115 (10.95%) patients had deteriorated KCCQ-12 scores. The correlation between the change in the KCCQ-12 score and NT-proBNP level was weak (r2 = 0.002, P = 0.013). Stratification by changes in the KCCQ-12 score revealed subgroups with distinctive risks, such that patients with deteriorated KCCQ-12 scores in any of the NT-proBNP change groups exhibited an increased risk of one-year all-cause death than participants with not deteriorated KCCQ-12 scores in any of the NT-proBNP change groups. For example, patients with improved NT-proBNP levels and deteriorated KCCQ-12 scores presented greater risks of one-year all-cause death (hazard ratio [HR]: 2.45, 95% confidence interval [CI]: 1.34-4.48) than patients with stable NT-proBNP levels and not deteriorated KCCQ-12 scores (HR [95% CI], 1.77 [1.25-2.53]).

A discrepancy between changes in NT-proBNP levels and KCCQ-12 scores was common. The change in NT-proBNP levels was not sufficient to characterize critical aspects related to HF during one month after discharge of patients. Changes in the KCCQ-12 score exhibit complementary information to NT-proBNP levels for the prediction of clinical outcomes in patients with acute HF.

www.clinicaltrials.gov (No. NCT02878811).

The potential impact of pre-existing coronary artery stenosis (CAS) on right ventricular (RV) function during acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and RV dysfunction in patients with acute PE.

In this multicenter, case-control study, 89 cases and 176 controls matched for age were enrolled at three study centers (Peking Union Medical College Hospital, Fuwai Hospital, and the Second Affiliated Hospital of Harbin Medical University) from January 2016 to December 2020. The cases were patients with acute PE with CAS, and the controls were patients with acute PE without CAS. Coronary artery assessment was performed using coronary computed tomographic angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression analysis was used to evaluate the association between CAS and RV dysfunction.

The percentages of RV dysfunction (19.1% [17/89] vs. 44.6% [78/176], P <0.001) and elevated systolic pulmonary artery pressure (sPAP) (19.3% [17/89] vs. 39.5% [68/176], P = 0.001) were significantly lower in the case group than those in the control group. In the multivariable logistic regression model, CAS was independently and negatively associated with RV dysfunction (adjusted odds ratio [OR]: 0.367; 95% confidence interval [CI]: 0.185-0.728; P = 0.004), and elevated sPAP (OR: 0.490; 95% CI: 0.252-0.980; P = 0.035), respectively.

Pre-existing CAS was significantly and negatively associated with RV dysfunction and elevated sPAP in patients with acute PE. This finding provides new insights into RV dysfunction in patients with acute PE with pre-existing CAS.

Huoxin Pill (HXP), a traditional Chinese medicine for cardiovascular diseases, demonstrates clinically reported anti-atrial fibrillation (AF) effects, though its mechanisms remain unclear. To investigate these mechanisms, we established an acetylcholine-calcium chloride (ACh-CaCl₂)-induced AF model in rats divided into control, AF, HXP (HXP-L: 3.33; HXP-M: 10; HXP-H: 30 mg/kg) and verapamil (25 mg/kg) groups. Following daily modelling, treatments were administered via gavage from Days 4 to 10. Electrocardiography (ECG) subsequently assessed AF susceptibility while echocardiography evaluated cardiac function. Systems pharmacology predicted HXP's targets/pathways for AF amelioration, with heart rate variability (HRV) and nerve activity recording examining autonomic balance. Electrical mapping quantified activation time (AT), conduction velocity (CV), conduction dispersion and effective refractory period (ERP) in isolated hearts. Results demonstrated that the AF group exhibited increased AF incidence/duration and decreased left ventricular ejection fraction/fractional shortening (LVEF/LVFS). Systems pharmacology revealed significant enrichment in cardiovascular pathways (including AF), while HRV and nerve recording indicated autonomic imbalance. Isolated AF hearts showed prolonged AT, slowed CV, increased conduction dispersion and shortened ERP. HXP significantly ameliorated these alterations. In conclusion, these findings suggest that HXP improves ACh-CaCl₂-induced AF, potentially through modulating autonomic nervous balance and atrial electrical conduction heterogeneity.

Cuproptosis is a recently identified form of copper-driven cell death characterized by the aggregation of acylated proteins and proteotoxic stress in the mitochondrial tricarboxylic acid cycle, which plays a role in inflammation. Recent studies suggest that hexokinase structural domain protein 1 (HKDC1), a fifth hexokinase, is involved in regulating mitochondrial function. However, the role of HKDC1 in cuproptosis and LPS-induced macrophage inflammation remains unclear. Here, we assess macrophage plasticity using CCK8 viability assays and phagocytosis activity experiments in an in vitro inflammatory model of THP-1 cells. We measure the levels of inflammatory factors and cuproptosis-related proteins using western blot analysis and RT-qPCR. Additionally, we examine the expression and localization of the HKDC1 protein using ChIP-qPCR and immunofluorescence staining. We find that LPS promotes the expressions of inflammatory factors and decreases cuproptosis levels in THP-1-derived macrophages while also activating glycolysis and inducing the expression of HKDC1 via the Toll-like receptor 4 (TLR4) receptor. We further demonstrate that HKDC1 knockdown inhibits glycolysis and induces cuproptosis. Mechanistically, we provide the first evidence that LPS promotes the binding of Yin Yang 1 (YY1) to the HKDC1 promoter, thereby regulating HKDC1 transcription. HKDC1 interacts with heat shock cognate B (HSCB) and ferredoxin 1 (FDX1), leading to increased intracellular copper levels and subsequent cuproptosis. HKDC1 knockdown in vivo alleviates acute sepsis by activating copper-dependent cell death pathways. Collectively, our findings suggest that LPS mitigates cuproptosis and promotes inflammation via HKDC1, suggesting a new cuproptosis-dependent anti-inflammatory strategy.

PurposeDemonstration of the role of autocrine motility factor receptor (AMFR) in atrial fibrillation (AF) mice.MethodsThe AF model was established by administering Ang II to mice and transfected with AMFR knockdown or AMFR overexpression plasmids by tail vein injection of the AAV vector. Atrial fibrosis was examined by Masson staining. The mRNA expression of inflammatory factors TNF-α, IL-1β, and IL-6 in atrial tissue was detected by PCR. Reactive oxygen species (ROS) production in atrial tissue was examined by dihydroethidium staining. Apoptotic cells of atrial tissue were examined by TUNEL staining. The expression levels of fibrosis-related genes (COL1A1 and α-SMA), apoptosis-related genes (cleaved-caspase3 and cleaved-PARP), and SOD1 were detected by western blot. The ubiquitination level of superoxide dismutase 1 (SOD1) was detected by ubiquitination assay.ResultsAng II resulted in increased AMFR expression in mouse atrial tissue, and knockdown of AMFR inhibited atrial fibrosis, inflammatory factors, and ROS production, as well as apoptosis in mice. In addition, the knockdown of AMFR inhibited the ubiquitination level of SOD1 and increased the protein expression level of SOD1, whereas overexpression of AMFR exerted the opposite effect and aggravated Ang II-induced AF.ConclusionKnockdown of AMFR promotes SOD1 expression by inhibiting SOD1 ubiquitination levels and attenuates atrial fibrosis in AF mice by regulating SOD1.

To identify the minimum dataset (MDS) for the monitoring of safety and effectiveness of GH in adults with growth hormone deficiency (AGHD).

Systematic review and expert consensus.

Outcomes for AGHD were identified through a systematic literature search in PubMed, Science Direct and Cochrane. In addition, 17 clinical experts from 10 countries and two patient representatives assembled through the Global Registry for Novel Therapies in Rare Bone and Endocrine Conditions (GloBE-Reg) provided data items that ideally should be collected routinely. These items were subsequently graded independently by participants on: (1) importance of the data field and (2) ease of data collection in routine clinical practice.

The systematic review identified 35 studies with 6732 participants with AGHD with a median age of 49 (range, 22-82) years. The common outcome categories included were cardiovascular in 21 (60%) studies, serum IGF-I in 13 (37%) and IGF-I SDS in 8 (23%), adiposity measures in 15 (44%) and psychosocial outcomes in 10 (29%). A total of 190 items were provided by experts and 86 (45%) achieved sufficient consensus and alignment with reported outcomes to create a final MDS with 45 items to be assessed, of which only 43 are manually entered.

This study has identified by consensus a minimum dataset considered necessary to provide consistency and comparability in global studies of AGHD.

Anthracycline-containing chemotherapy is associated with cardiovascular diseases (CVDs). While knowledge regarding the extent of cardiotoxicity in adult patients with acute myeloid leukaemia (AML) is sparse, anthracyclines remain a key component in the treatment. To address this, 1379 adult AML patients treated with anthracycline-containing chemotherapy between 2000 and 2020 were matched to 6895 comparators from the Danish background population and followed for a median of 11.8 and 12.8 years respectively. The risk of congestive heart failure (CHF) was higher in AML patients compared to the comparators throughout the entire follow-up period with adjusted hazard ratios (HRs) ranging from 15.0 (95% CI: 7.02-32.1) after 3 months to 2.68 (95% CI: 1.67-4.30) after 15 years. The risk of non-CHF CVD was initially higher in AML patients (adjusted HR: 9.16 [95% CI: 6.61-12.7] after 3 months) but converged to that of the comparators after approximately 10 years. Among AML patients, increasing age and male sex were identified as risk factors of CHF and non-CHF CVD. In summary, AML patients treated with anthracycline-containing chemotherapy had an elevated risk of CVD, particularly during the first years after treatment initiation. Increased focus on early detection and cardioprotective strategies may help mitigate the harmful effects of anthracyclines in the future.

Chronic subclinical inflammation, which gradually increases with age, is a major risk factor in the development of several chronic diseases, including cardiovascular disease, type 2 diabetes, cancer, and mental disorders. Environmental factors, including air pollution and lifestyle, influence subclinical inflammation. However, evidence of the influence of ambient temperature (AT) on subclinical inflammation is limited. This study addresses this gap by examining the association between AT and biomarkers of subclinical inflammation in a cohort of older German women. We investigated 359 women (age range: 68.6 - 79.1 years) from the German SALIA cohort during the 2007-2010 follow-up. Data on 12 plasma biomarkers of subclinical inflammation, climatic factors (AT and relative humidity), and air pollution were collected and analyzed. Linear regression models with moving average lag periods (lag 0-1, lag 0-2, …, lag 0-14) were used to estimate associations, adjusting for age, BMI, smoking, alcohol consumption, socioeconomic status, cardiovascular disease, and respiratory disease. We observed consistent and significant associations between higher AT and increased levels of TGF-β1 and MCP-1/CCL2, as well as between higher AT and decreased levels of C3c and sICAM-1. For example, the lag 0-7 moving average results showed that a 5 °C increase in AT was associated with a 9.97% increase in TGF-β1 (95% CI: 1.54%, 19.10%), an 8.96% increase in MCP-1/CCL2 (95% CI: 4.38%, 13.75%), a 5.84% decrease in C3c (95% CI: -8.87%, -2.71%), and a 3.97% decrease in sICAM-1 (95% CI: -7.22%, -0.59%). These findings underscore the role of environmental factors in subclinical inflammation and the link between AT and immune mediators associated with chronic disease risk.

Sex-specific evidence on de-escalation strategies of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention in patients with acute coronary syndromes (ACS) remains limited. Females are often under-represented in randomized controlled trials (RCTs) and sex-based subgroup analysis in RCTs yield conflicting results. We searched PubMed and EMBASE in September 2024 for RCTs that investigated DAPT strategies for patients with ACS. We examined whether there are differences in the efficacy and safety of de-escalation strategies (i.e., short-term DAPT (≤6 months), unguided de-escalation, and guided de-escalation with genotype or platelet function tests) compared to standard DAPT (12 months) between sexes. A systematic review and meta-analysis were performed to compare the efficacy and safety between sexes with p-value for test of moderators. The primary efficacy outcome was major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular death, myocardial infarction, and stroke. The primary safety outcome was major or minor bleeding. Fourteen RCTs involving 35,901 patients with ACS (7,652 female patients, 28,249 male patients) were included. The effect of de-escalation strategies on the primary efficacy outcome was significantly different between female (HR, 0.74; 95% CI, 0.57-0.95; I²=0%) and male patients (HR, 1.04; 95% CI, 0.90-1.19; I²=15%), with p-value for test of moderators 0.019. The primary safety outcome showed no significant sex differences (p-value for test of moderators=0.67). In conclusions, in patients with ACS, compared to standard DAPT, de-escalation strategies were more effective in reducing MACE in female than in their male counterparts. Meanwhile, de-escalation strategies were similarly safer for both sexes.