Patient-reported outcome measures (PROMs) are vital tools in cardiovascular disease (CVD) research and care, providing insights that complement traditional clinical outcomes like mortality and morbidity. PROMs capture patient experiences with CVD, such as quality of life, functional capacity, and emotional well-being, allowing clinicians to assess how interventions impact daily life. PROMs are integral to cardiovascular investigations as well as management, especially in chronic conditions and rehabilitation, where they inform on the impact of personalized care plans by tracking symptom progression and patient adherence. Selecting and applying to cardiovascular research and practice effective PROMs involves evaluating their validity, reliability, and sensitivity to change, with instruments like the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Seattle Angina Questionnaire (SAQ) widely used for heart failure and coronary artery disease, respectively. Implementing PROMs in real-world practice requires addressing challenges related to workflow integration and patient adherence, emphasizing their value in patient-centered care. As digital health advances, remote PROM data collection through mobile applications and wearable devices will enhance access to and extent of PROMs, and AI-driven analytical tools will provide real-time, automated and plausible more poignant insights for personalized treatment. Future efforts should focus on culturally adapting PROMs for diverse populations to ensure global applicability. PROMs should also be established as essential components of innovative research and responsive, patient-centered cardiovascular care.

Pulmonary vascular remodeling and arterial hypertension (PAH) correlate to increased platelet-derived growth factor (PDGF) 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 treatment of PAH. A literature search was conducted with the PubMed, Embase, Web of Science, and Cochrane Library to obtain randomized controlled trials (RCTs) where the efficacy of imatinib and placebo in PAH patients was compared. Three RCTs that involved 262 patients were finally included in this study. Results showed that imatinib significantly improved six-minute walk distance (MD = 42.76, 95% CI [9.20 - 76.32], P = 0.01), reduced pulmonary vascular resistance (MD = -396.68, 95% CI [-474.50 - -318.85], P < 0.00001), and lowered mean pulmonary arterial pressure (MD = -7.29, 95% CI [-13.97 - -0.61], P = 0.03) in PAH patients. No significant difference was found between the imatinib and placebo groups in terms of mortality (OR = 1.25, 95% CI [0.49 - 3.18]) or adverse events (OR = 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 PAH patients warrants further studies.

Sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and angiotensin receptor-neprilysin inhibitor (ARNI) may cause potential renal damage, the combined impact of SGLT2Is and ARNI on acute kidney injury (AKI) remains unclear. This pharmacovigilance study conducted a disproportionality analysis using reports from the FDA Adverse Event Reporting System database. The reporting odds ratio was used as an estimate for detecting AKI signal. A total of 659,573 reports on at least 1 glucose-lowering drug and/or ARNI were obtained. Of the 413 reports on cotherapy of SGLT2Is and ARNI, 99 (24.0%) reports mentioned AKI. Overall, the AKI reporting rate significantly increased in cotherapy (adjusted reporting odds ratio, 95% confidence interval: 8.04, 6.20-10.42, P < 0.001), with a stronger AKI signal in cotherapy of canagliflozin and ARNI (16.82, 3.75-75.57, P < 0.001). Specifically, no increased AKI signal was detected in patients with heart failure (HF) receiving cotherapy after adjustment for sex and age (HF: 1.27, 0.89-1.80, P = 0.189; HF plus diabetes: 2.08, 0.99-4.40, P = 0.055; or HF plus hypertension: 1.69, 0.53-5.35, P = 0.376), whereas enhanced AKI signals were detected in patients with diabetes (20.57, 11.93-35.46, P < 0.001), hypertension (4.30, 1.98-9.37, P < 0.001), or diabetes plus hypertension (5.44, 1.92-15.43, P = 0.001). This study reveals that superimposed renal impairment results from cotherapy with SGLT2Is and ARNI. It is necessary to be vigilant that the elderly patients with diabetes, hypertension, or chronic kidney disease are more susceptible to AKI, especially if they likewise receive diuretics. When cotherapy is unavoidable, early monitoring of renal function, blood volume, and blood pressure is excessively crucial. However, it is relatively safe in patients with HF.

Receptors for the vasoactive adipokine apelin, termed APJ receptors, are G-protein-coupled receptors and are widely expressed throughout the cardiovascular system. APJ receptors can also signal via G-protein-independent pathways, including G-protein-coupled-receptor kinase 2 (GRK2), which inhibits nitric oxide synthase (eNOS) activity and nitric oxide (NO) production in endothelial cells. Apelin causes endothelium-dependent, NO-mediated relaxation of coronary arteries from normotensive animals, but the effects of activating APJ receptor signaling pathways in hypertensive coronary arteries are largely unknown. We hypothesized that apelin-induced relaxation is impaired in coronary arteries from spontaneously hypertensive rats (SHR). Western blot and mRNA analysis revealed increased GRK2 expression in cultured SHR coronary endothelial cells. Apelin failed to cause relaxation in isolated SHR coronary arteries but, in the presence of apelin, relaxations to acetylcholine (ACh) were impaired. Apelin had no effect on relaxation to DEA NONOate. The GRK2 inhibitor, CMPD101, increased apelin-induced phosphorylation of Akt and eNOS in SHR endothelial cells and restored relaxation to apelin in SHR arteries. CMPD101 also blocked the inhibitory effect of apelin on ACh-induced relaxation. Relaxations to the APJ receptor-biased agonist, CMF-019, which preferentially activates the G-protein-dependent pathway with minimal effect on GRK2, were similar in SHR and WKY coronary arteries. Immunoblot analysis in SHR coronary endothelial cells demonstrated that CMF-019 increased Akt and eNOS phosphorylation whereas apelin had no effect. Thus, APJ receptor signaling via GRK2 impairs NO production or release from SHR endothelial cells. APJ receptor-biased agonists, such as CMF-019, may be more effective than apelin in causing vasodilation of SHR coronary arteries.

Positive inotropic responses upon administration of milrinone, an inhibitor of the phosphodiesterase enzyme (PDE), involve a well-pronounced positive chronotropic effect. Here we tested whether milrinone evokes this chronotropic response solely by PDE inhibition or by a concerted action that involve additional pharmacological targets. Milrinone stimulated increases in heart rate were studied in right atrial preparations of guinea pig in the presence or absence of inhibitors of putative ancillary molecular pathways or ion channels: i.e. β receptor blockers with distinct selectivities (propranolol, metoprolol, and carvedilol), α1 receptor blocker (prazosin), inhibitor of the small conductance Ca2+ activated K+ (SK) channels (apamin), L-type Ca2+ channel blockers (verapamil and diltiazem), and different Na+ channel blockers (lidocaine, tetrodotoxin, and quinidine). Carvedilol, which inhibits β1, β2, α1 and 5-HT receptors, limited the positive chronotropic effects of milrinone to about 40%, (p<0.01). In the presence of another non-selective blocker of the β receptors, propranolol, and blockers of the L-type Ca2+ channels, only non-significant trends towards reductions of the milrinone effects were seen. The α1 receptor blocker prazosin did not limit the milrinone evoked positive chronotropy. Blockers of Na+ channels, SK channels, or the β1 receptor blocker, metoprolol also did not affect the positive chronotropy evoked by milrinone. We conclude that milrinone increases heart rate in response to adrenergic signaling, that besides PDE inhibition, may involve a 5-HT-receptor-dependent component. Our exploratory approach paves the way to more focused experiments with the use of selective 5-HT-receptor antagonists to confirm or reject the involvement of a specific 5-HT-receptor dependent pathway.

In this study, we compared the effects of various doses of dexmedetomidine on the incidence of atrial fibrillation following cardiac surgery in adults. 224 adult patients who underwent elective cardiac surgery were randomly assigned to two groups. The DEX0.5 group received a continuous infusion of dexmedetomidine at a rate of 0.5 μg·kg⁻1·h⁻1, while the DEX1 group received it at a rate of 1 μg·kg⁻1·h⁻1 during the induction of anesthesia, which was maintained for 24 hours. The primary outcome was the incidence of atrial fibrillation, while the secondary outcomes included other tachyarrhythmias, bradycardia, hypotension, duration of mechanical ventilation, time spent in the cardiac care unit, and length of hospitalization. A total of 101 patients were included in the DEX0.5 group, while 104 patients were included in the DEX1 group. The incidence of atrial fibrillation was significantly lower in the DEX1 group compared to the DEX0.5 group (10.6% vs. 21.8%, P = 0.029). Additionally, the duration of mechanical ventilation was shorter in the DEX1 group than in the DEX0.5 group (8.9 vs. 15.2 hours, P = 0.018). Logistic regression analyses were conducted to investigate the factors influencing atrial fibrillation. The results indicated that the dose of dexmedetomidine was the only independent predictor (odds ratio = 0.394, 95% confidence interval 0.172 to 0.903, P = 0.028). Compared to a continuous infusion of 0.5 μg·kg⁻1·h⁻1, this study suggested that administering dexmedetomidine at a dose of 1 μg·kg⁻1·h⁻1 for 24 hours is effective in reducing the incidence of atrial fibrillation following cardiac surgery.

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 following 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 non-paroxysmal 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 (HFrEF) 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 HFrEF and in the overall patient population, independent of AF phenotype.

Transthyretin amyloidosis (ATTR) is characterized by the deposition of unstable transthyretin protein (TTR) in the heart or peripheral nerves. Therapeutic strategies for ATTR include inhibition of the secretion of abnormal TTR by the liver, reducing the concentration of aberrant TTR in the circulation, and eliminating amyloid deposits of TTR in tissues. This article delves into the pathogenesis of TTR secretion from the liver into the bloodstream, its deposition in tissues, and the subsequent development of ATTR. Additionally, we delineated the advancements in treatment strategies and discussed future research directions to provide novel insights for the identification of diagnostic and preventive targets.

It is unclear whether drugs other than warfarin can cause spontaneous gastrointestinal intraluminal hematomas (SGIH). This study aimed to investigate the drugs that induced SGIH based on the FDA Adverse Event Reporting System (FAERS) data. A retrospective pharmacovigilance study was conducted. The disproportionality analysis was performed to assess the reports of drug-induced SGIH from the first quarter of 2004 to the fourth quarter of 2023. Logistics regression analysis was used to explore drug-related SGIH risk factors. Weibull distribution was applied for the onset time of SGIH. A total of 116 drugs associated with SGIH have been reported in the FAERS database. After removing duplicates, 88 unique drugs involving 210 patients were identified. These drugs can be broadly classified into four categories: (1) anticoagulants, (2) new direct oral anticoagulants, (3) antiplatelet agents, and (4) others. The first group is dominated by warfarin (59/210), while the second group, rivaroxaban, accounts for the most significant proportion (9/210). As for the third group, aspirin is the dominant drug (16/210), and for the fourth group, drugs that cause thrombocytopenia are dominant. The median number of reported cases was 11.5 per year, accounting for a median percentage of 0.0094% of all adverse events related to target drugs. The median time to drug-related SGIH onset was 12.5 days (interquartile range 1-220.25 days). When patients on the related drugs present with corresponding abdominal symptoms, it is crucial to consider the differential diagnosis of SGIH despite its low incidence.

Isorhynchophylline is a Chinese herbal medicine and has multiple effects such as anti-inflammatory and neuroprotective effects. Whether isorhynchophylline has anti-thrombotic property is unknown. This study aims to evaluate its role in platelet function. Human platelets were incubated with isorhynchophylline (0, 10, 20 and 40 μM) at 37°C for 1 hour to detect platelet aggregation and activation, receptors level, spreading and calcium mobilization. Additionally, isorhynchophylline (5 mg/kg) was injected into mice to measure in vivo hemostasis and thrombosis. Isorhynchophylline dose-dependently reduced platelet aggregation, ATP secretion, P-selectin expression and αIIbβ3 activation induced by collagen-related peptide (CRP) or thrombin without affecting surface level of receptors αIIbβ3, GPIbα, and GPVI. Meanwhile, isorhynchophylline-treated platelets showed reduced spreading. Moreover, isorhynchophylline reduced platelet calcium mobilization, phosphatidylserine exposure and the phosphorylation of PLCγ2 and PKCα. Furthermore, administration of isorhynchophylline into mice impaired platelet hemostatic function and arterial/venous thrombosis without affecting coagulation. In conclusion, Isorhynchophylline impairs platelet function and arterial/venous thrombosis, implying its potential to be a novel agent for treating thrombotic or cardiovascular diseases.

The study aimed to develop a radiomics model to assess carotid artery plaque vulnerability using CTA images. It retrospectively included 107 patients with carotid artery stenosis who underwent carotid artery stenting (CAS) 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 pre-treatment CTA images. Radiomics features were extracted and reduced using the LASSO method to minimize redundancy. A radiomics model was then constructed, utilizing 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 (AUC 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 AUC values of 0.985 and 0.961 in the training and testing groups, respectively. Decision curve analysis (DCA) indicated that the combined model offered superior clinical benefits over 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.

Adrenergic overstimulation is detrimental to the left ventricle. However, its effects on the right ventricle (RV) are not clear. Since adrenergic overload increases metabolic demand and oxidative stress, boldine could be a therapeutic option in the treatment of cardiovascular disease due to its antioxidant role. This study aimed to investigate the impact of adrenergic overload on RV remodelling and the cardioprotective effect of boldine. Animals were divided into four groups: control (C), boldine (25 mg/kg i. p.) (B), isoproterenol (5 mg/kg subcutaneously) (ISO), and boldine+isoproterenol (B+ISO). Echocardiography, Fulton index, histology, oxidative stress, inflammation, and β-adrenergic receptor (ADR) were analysed. The diastolic parasternal length [C 0.698 (0.623-0.724) vs ISO 0.77 (0.73-0.81)], Fulton index [C 0.268 (0.231-0.275) vs ISO 0.340 (0.280-0.353)], inflammatory infiltration (∼40%), and ADR [C 0.78 (0.71-0.84) vs ISO 1.74 (1.52-2.00)] were increased in the ISO group (P<0.05). Boldine treatment (B+ISO) reduced the Fulton index [0.240 (0.228-0.263)], lipid peroxidation [2.07 (2.01-2.61)], and ADR [0.71(0.62-0.80)]. Boldine increased total SH levels in B+ISO [C 2.4 (1.78-2.71); ISO 4.01 (2.95-4.66) vs B+ISO 6.77(5.15-8.60)] (P<0.05). There was a positive correlation between lipid peroxidation and the Fulton index, and a negative correlation between total SH and the Fulton index (P<0.05). This is the first study to explore the effects of adrenergic overstimulation on RV and the protective effect of boldine. Such data pave the way for further research involving RV remodelling, such as in pulmonary hypertension, as well as a new therapeutic option.

Loop diuretics are a fundamental cornerstone in management of hypervolemia encountered in acute decompensated heart failure. There is variation in literature describing relative potency of loop diuretic agents, and 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 utilized to determine comparison groups. The primary outcome was total urine output for 24 hours following 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 versus 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 the acute decompensate heart failure.

Given the high prevalence of cardiovascular disease in the United States, there is a critical need for new medications to improve outcomes of these diseases. The U.S. Food and Drug Administration (FDA) has approved numerous medications that are able to effectively do so. While these drugs have significantly beneficial effects, just like any other medication, they can come with a multitude of unwanted side effects. It has been noted that cardiovascular drugs have been associated with a considerable number of dermatologic reactions. This review examines current literature on the various cutaneous manifestations of these adverse reactions. It focuses on these newly FDA-approved cardiovascular medications from 2013 to 2023, detailing both common and rare effects in the past decade. As more medications continue to enter the market, the necessity for awareness of more systemic side effects will continue to grow. This comprehensive review aims to guide clinicians in identifying drug-induced reactions in patients on these therapies.

In a randomized double-blinded clinical trial of patients with ST segment elevation myocardial infarction (STEMI), goflikicept, an interleukin-1 blocker, significantly reduced systemic inflammation, measured as the area under the curve (AUC) for high-sensitivity C reactive protein at 14 days. We report secondary analyses of biomarkers at 28 days, and cardiac function and clinical end points at 1 year. Patients received a single administration of goflikicept 80 mg (n = 34), goflikicept 160 mg (n = 34), or placebo (n = 34). Both doses of goflikicept significantly reduced the AUC for high-sensitivity C reactive protein at 28 days compared with placebo, without statistically significant differences between the doses. There were no statistically significant differences between groups in the AUC for natriuretic peptides at 28 days. There were no significant differences between placebo, goflikicept 80 mg, and 160 mg groups in deaths (2.9%, 2.9%, and 0%), hospitalization for cardiovascular reasons (9.1%, 5.9%, and 0%), new-onset or progression of heart failure (9.1%, 5.9%, and 5.9%), and new or increased use of loop diuretics (24.2%, 14.7%, and 17.6%), nor in the number of patients with treatment emergent adverse events, with no treatment-related serious adverse events in any group. In conclusion, in patients with STEMI, interleukin-1 blockade with goflikicept 80 mg or 160 mg was well tolerated and associated with significant reduction of systemic inflammation. Further adequately powered studies are warranted to determine whether the reduction in systemic inflammation with goflikicept translates into a clinical benefit in patients with STEMI.

Large scale randomized trials have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors can reduce cardiovascular events in patients with cardiovascular disease or with increased risks of cardiovascular disease. However, the evidence from older patients is limited. To compare the efficacy of SGLT2 inhibitors among non-older and older patients we have searched PubMed, Cochrane Central, and Embase until February 2023 for randomized controlled trials (RCTs) investigating SGLT2 inhibitors in older (age ≥ 65 years) patients with diabetes mellitus, chronic kidney disease, and chronic heart failure. The primary outcome was a composite outcome of cardiovascular death, acute myocardial infarction, and stroke. The secondary outcomes were exacerbation of heart failure, kidney disease progression, and a composite of cardiovascular death and heart failure. Our search identified 11 RCTs with a total of 79,370 patients. SGLT2 inhibitors were associated with a reduced risk of the primary outcome in the total cohort (HR: 0.91; CI [0.84-0.99]) with concordant results in both non-older and older populations (HR: 0.96; CI [0.88-1.05], HR: 0.87; CI [0.75-1.01], respectively) without subgroup differences (p=0.23), and a reduced risk of developing the composite of cardiovascular death and heart failure exacerbation in both non-older and older populations (HR: 0.77; CI [0.67-0.87], HR: 0.76; CI [0.71-0.82], respectively) without subgroup differences (p=0.96). A meta-analysis could not be performed for the other outcomes. These results suggested that SGLT2 inhibitors were similarly associated with a reduced risks of cardiovascular events across the spectrum of non-older and older patients with risk factors for developing cardiovascular disease.

The number of patients living with chronic kidney diseases is increasing, and so are the patients with end-stage renal disease (ESRD) undergoing renal replacement therapy (RRT). While there is a common understanding that these patients face higher risks of fatal or non-fatal cardiovascular and cerebrovascular events, and mineralocorticoid receptor antagonists (MRA) have been an essential pillar in managing heart failure, their use in this subset of patients have been overshadowed due to concerns of hyperkalemia. ESRD patients under RRT have often been excluded from landmark trials. This meta-analysis was conducted based on the PRISMA guideline after registering the protocol with PROSPERO (CRD42024499835). A database search included articles until April 2024 and relevant data extracted from the included studies. Analysis was done using RevMan web (version 5.4). A total of 15 studies among 1086 studies were included in the final analysis. Our meta-analysis revealed MRA significantly reduced all-cause mortality (OR 0.35, CI 0.23- 0.54) and cardio-vascular mortality (OR 0.37, 0.21-0.65). With some possible increase in the risk of hyperkalemia (OR 1.56, CI 1.01-2.42), with no discernible difference in the occurrence of stroke (OR 0.57, CI 0.25-1.28) or MI (OR 0.63, CI 0.08-4.72). The utilization of MRA in patients with ESRD under dialysis is linked to improved mortality outcomes, albeit with slight concerns for hyperkalemia. While current evidence leans towards MRA usage, prospective randomized controlled trials involving a broader patient cohort are essential to establish robust guidance for MRA application in this subset of patients.

This study aimed to explore the relationship between the changes in early degradation products of polysaccharide coatings (such as hyaluronic acid (HA), syndecan-1 (SDC-1), and heparan sulfate (HS)) and the development of organ dysfunction in sepsis patients. We conducted a retrospective analysis on 140 sepsis patients admitted from January 2021 to June 2022, who formed the study group; 100 healthy individuals who underwent health checks during the same period were included as the control group. The study found that the expression levels of HA, SDC-1, and HS upon admission and within 24 hours of admission in sepsis patients, as well as the early change rates, were positively correlated with organ dysfunction (P < 0.05). Through receiver operating characteristic (ROC) curve analysis, we discovered that the early change rates of HA, SDC-1, and HS have high predictive value for organ dysfunction in sepsis patients, with the combined predictive value being the most significant. The study conclusion points out that the increased levels of HA, SDC-1, HS, and other degradation products of polysaccharide coatings in the early stage of sepsis are positively associated with the occurrence of organ dysfunction. Clinicians can utilize the early expression changes of these biomarkers to predict the risk of organ dysfunction in sepsis patients, enabling timely implementation of preventive measures that may improve patient outcomes.