Journal of Cardiovascular Pharmacology最新文献

Thoracic aortic aneurysm (TAA) is a life-threatening condition that currently lacks an effective therapeutic strategy. Phenotypic switching in vascular smooth muscle cells (VSMCs) and extracellular matrix (ECM) degradation are considered to be among the causes of TAA development. Trimethylamine N-oxide (TMAO) is a gut microbial metabolite that has been associated with the increased risk of cardiovascular diseases. However, its general association with TAA remains unclear. Therefore, the present study aimed to assess the possible role of TMAO in TAA development. In the mouse TAA model, TMAO exacerbates aortic dilation and degeneration, promoting the development of thoracic aortic aneurysm. Furthermore, TMAO was observed to impair murine cardiac function. In vitro, it was demonstrated that TMAO inhibited proliferation whilst promoting migration and apoptosis in VSMCs. RNA-sequence analysis of TMAO targets subsequently identified Axl and a cohort of genes associated with extracellular matrix signaling. Mechanistically, it was found that TMAO inducing a shift from a contractile to a synthetic phenotype by inhibiting Axl. Overexpressing Axl suppresses this transition. In summary, TMAO worsens TAA progression by impairing vascular smooth muscle cell function, and restoring Axl expression can counteract the phenotypic shift caused by high TMAO levels. Thus, targeting the TMAO-Axl regulatory axis could be a therapeutic strategy for TAA patients with elevated TMAO expression.

Air pollution is associated with excess thrombotic and cardiovascular events. However, clinical outcomes trials evaluating interventions to mitigate such adverse events in patients with atherosclerotic cardiovascular diseases (ASCVD) are lacking. This is a single-center, open-label, feasibility randomized controlled trial (RCT) conducted in adult patients with documented ASCVD. Participants were randomized to a hybrid strategy consisting of an educational flashcard, educational cell phone text message alerts on polluted days to stay indoors, use KN95 masks if they need to go outside, and to consume citrus fruits on polluted days, versus usual care. The main objectives were to assess the feasibility of enrollment and adherence to and satisfaction with the hybrid strategy along with health-related quality of life and anxiety level. Between January 28, 2024, and February 18, 2024, 130 patients were screened, of whom 50 (38.5%) were randomized. During the study period, 12 polluted days occurred, and patients received a median of 8 ((IQR) 8 to 10) alerts. The majority adhered to all components on all polluted days, including full adherence for reading flashcards in 56%, avoiding outdoor activities in 52%, wearing KN-95 facemasks if they went out in 81.8%, and self-reported citrus fruit consumption in 84% of enrollees. The most participants in the intervention arm were satisfied with all components of the hybrid staretgy. Quality of life index and anxiety level remained unchanged for both groups during the 30-day follow-up. This pilot study shows the feasibility of recruitment to multifaceted strategy to mitigate the cardiovascular effects of air pollution with high adherence and satisfaction, thus supporting initiatives to design and conduct a large-scale RCT to validate and extend these findings.

Abstract: Loop diuretics are a fundamental cornerstone in management of hypervolemia encountered in acute decompensated heart failure. There is variation in the literature describing relative potency of loop diuretic agents, and there are very limited available data specific to the heart failure population. In this retrospective cohort study, we aimed to compare the urine output response between intravenous furosemide and bumetanide in patients with acute decompensated heart failure. Patients were eligible for inclusion if they were admitted between July 1, 2021, and June 30, 2022, with acute decompensated heart failure and received intravenous bumetanide or furosemide within 48 hours of admission. Propensity matching was used to determine comparison groups. The primary outcome was total urine output for 24 hours after initiation of the diuretic regimen. A total of 120 patients (60 in each group) were matched after exclusion criteria were applied. The total urine output was similar between groups. The bumetanide group did demonstrate a greater urine output: furosemide-equivalent response (52 ± 46 mL/mg vs. 33 ± 25 mL/mg; P = 0.007). Based on our analysis, similar urine output may be achieved with either intravenous bumetanide or furosemide in acute decompensated heart failure; however, a higher dose of furosemide may be required than what has been previously established as an equivalent dose to bumetanide to achieve a similar diuretic effect. These results should warrant further investigation to better establish dose-response relationships with loop diuretics in acute decompensated heart failure.

Abstract: Pulmonary vascular remodeling and arterial hypertension (PAH) correlate with increased platelet-derived growth factor activity and elevated KIT expression. Imatinib has emerged as a potential therapeutic agent for PAH. The purpose of this systematic review and meta-analysis was to assess the effectiveness of imatinib in the treatment of PAH. A literature search was conducted with the PubMed, Embase, Web of Science, and Cochrane Library to obtain randomized controlled trials where the efficacy of imatinib and placebo in patients with PAH was compared. Three randomized controlled trials that involved 262 patients were finally included in this study. Results showed that imatinib significantly improved 6-minute walk distance (mean difference [MD] = 42.76, 95% confidence interval [CI], 9.20-76.32, P = 0.01), reduced pulmonary vascular resistance (MD = -396.68, 95% CI, -474.50 to -318.85, P < 0.00001), and lowered mean pulmonary arterial pressure (MD = -7.29, 95% CI, -13.97 to -0.61, P = 0.03) in patients with PAH. No significant difference was found between the imatinib and placebo groups in terms of mortality (odds ratio = 1.25, 95% CI, 0.49-3.18) or adverse events (odds ratio = 1.82, 95% CI, 0.76-4.36, P = 0.18). Despite the significant improvement of key hemodynamic parameters, there was no advantage in reducing clinical adverse events or mortality. The prolonged efficacy and safety of imatinib in patients with PAH warrant further studies.

Abstract: Although sodium-glucose cotransporter 2 inhibitors (SGLT2i) are known to reduce the incidence of atrial fibrillation (AF) and AF-related adverse events, evidence on their prognostic effect in patients undergoing catheter ablation (CA) for AF is limited. In a single center, 614 patients (mean age 58.1 ± 9.9 years, 42.2% female) who underwent CA for AF were retrospectively divided into 2 groups according to SGLT2i treatment after the index procedure and followed up for 24 months. The primary outcome of the study was AF recurrence after the first 90-day blanking period after CA. Two separate Cox regression models were constructed to determine the predictors of AF recurrence. Rates of the primary outcome were 19.4% and 35.7% in the SGLT2i and non-SGLT2i groups, respectively. According to the multivariable model 1, which was established among the clinically relevant variables that were found to be statistically significant in univariable analysis, left atrial diameter (adjusted HR: 1.087, 95% CI, 1.054-1.122, P < 0.001), SGLT2i therapy (adjusted HR: 0.436, 95% CI, 0.286-0.665, P < 0.001), and nonparoxysmal AF (adjusted HR: 1.549, 95% CI, 1.039-2.309, P = 0.032) were independent predictors of recurrence after ablation. In model 2, SGLT2i treatment remained an independent predictor of AF recurrence along with significant variables such as age, heart failure with reduced ejection fraction, and previous stroke (adjusted HR: 0.315, 95% CI, 0.214-0.461, P < 0.001). The favorable efficacy of SGLT2i on the primary outcome was maintained in subgroup analyses. SGLT2i treatment is associated with lower recurrence after CA for AF in subgroups with and without diabetes or heart failure with reduced ejection fraction and in the overall patient population, independent of AF phenotype.

Abstract: Intravenous (IV) digoxin loading dose (LD) recommendations for rate control of atrial arrhythmias in critically ill patients are not well studied. When using digoxin in the setting of atrial fibrillation/atrial flutter (AF/AFL), a LD in either a fixed-dose regimen, weight-based dose, or pharmacokinetic-based calculation to target a serum digoxin concentration (SDC) of 0.8-1.5 ng/mL is recommended. The objective of this study was to assess the safety and effectiveness of digoxin LD used in critically ill patients for rate control of AF/AFL and to assess the SDC achieved. This single-center retrospective cohort study included patients, who received IV digoxin and had a SDC drawn. The primary endpoint was the median SDC achieved after a digoxin LD. Secondary outcomes included the frequency of SDCs ≥1.5 ng/mL and heart rate control. A total of 92 patients were included. The median total LD of digoxin for the entire cohort was 11 μg/kg (750 μg). For 61% of the cohort, the LD was distributed over 6-hour intervals. The median SDC after completion of the IV digoxin LD was 1.3 ng/mL (0.9-1.7). The incidence of supratherapeutic SDC was 36% for the total cohort. A target heart rate <110 beats per minute within 24 hours from digoxin LD was achieved in 60% of the cohort. In conclusion, a median total digoxin LD of 750 μg in critically ill patients with AF/AFL, targeting a SDC <1.5 ng/mL, may be considered for acute rate control, taking into account drug-drug interactions in the cardiac intensive care unit. Future studies are necessary to confirm our findings.

Abstract: The study aimed to develop a radiomics model to assess carotid artery plaque vulnerability using computed tomography angiography images. It retrospectively included 107 patients with carotid artery stenosis who underwent carotid artery stenting from 2017 to 2022. Patients were categorized into stable and vulnerable plaque groups based on pathology. A training group and a testing group were formed in a 7:3 ratio. Clinical data, including demographics and lipid profiles, were collected alongside pretreatment computed tomography angiography images. Radiomics features were extracted and reduced using the LASSO method to minimize redundancy. A radiomics model was then constructed, using 13 features with a minimum penalty coefficient logλ = 0.047. Significant differences were found between stable and vulnerable plaques in terms of stenosis degree. The radiomics model showed high accuracy (area under the curve of 0.959 in training and 0.942 in testing) for identifying vulnerable plaques. When combined with clinical parameters stenosis degree, the model's diagnostic efficacy improved further, with area under the curve values of 0.985 and 0.961 in the training and testing groups, respectively. Decision curve analysis indicated that the combined model offered superior clinical benefits for the clinical model and radiomics model alone. The study concludes that the combined radiomics model, incorporating stenosis degree, presents a promising tool for differentiating vulnerable from stable plaques.