Early ß-blocker use and in-hospital outcomes in patients with chronic obstructive pulmonary disease hospitalized with acute coronary syndrome: findings from the CCC-ACS project.

Background: Patients with chronic obstructive pulmonary disease (COPD) after acute coronary artery syndrome (ACS) are at an increased risk of heart failure and death. However, ß-blockers have been underused in this population group due to concerns of adverse reactions. Objective: This study aims to investigate the ß-blocker prescription at admission and its impact on the in-hospital outcomes in patients with COPD after ACS in a Chinese national cohort. Methods: Among 113,650 patients with ACS enrolled in the national registry of the Improving Care for Cardiovascular Disease in China between November 2014 and July 2019, a total of 1,084 ACS patients with COPD were included in this study. The primary endpoint was in-hospital mortality, and the secondary endpoint was the composite of in-hospital all-cause death and heart failure. Results: Early oral ß-blocker therapy was administered to 49.8% of patients. The Kaplan-Meier analysis showed that the early ß-blocker treatment group had lower all-cause mortality (0.9% vs. 2.9%; P < 0.05) and lower combined endpoint event rate (8.2% vs. 12.0%; P < 0.05) compared to the those of the non-early ß-blocker treatment group. The analysis of inverse probability of treatment weighting showed that the early ß-blocker treatment group was associated with a significantly reduced incidence of all-cause death (risk ratio, 0.332, 0.119-0.923, P = 0.035), heart failure (risk ratio, 0.625, 95% CI 0.414-0.943, P = 0.025), and combined endpoint events (risk ratio: 0.616, 95% CI: 0.418-0.908, P = 0.014). In the subgroup of patients over 70 years of age, the corresponding hazard ratio was 0.268 (95% CI 0.077-0.938) for all-cause mortality and 0.504 (95% CI 0.316-0.805) for combined endpoint events. Conclusion: ß-blockers have been underused in patients with COPD and ACS in China. Early ß-blocker therapy is associated with an improvement in in-hospital outcomes in patients with COPD after ACS. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT02306616).

The clinical value of ß-blockers in patients with stable angina.

Stable angina, one manifestation of chronic coronary syndrome (CCS), is characterised by intermittent episodes of insufficient blood supply to the myocardium, provoking symptoms of myocardial ischaemia, particularly chest pain. These attacks usually occur during exercise or stress. Anti-ischaemic drugs are the mainstay of pharmacologic management of CCS with symptoms of angina. ß-blockers reduce heart rate and myocardial contractility, thus reducing myocardial oxygen consumption. These drugs have been shown to ameliorate the frequency of anginal attacks and to improve exercise capacity in these patients. Current management guidelines include ß-blockers as a first-line management option for most patients with CCS and symptoms of myocardial ischaemia, alongside dihydropyridine calcium channel blockers (CCB). The presence of comorbid angina and heart failure is a strong indication for starting with a ß-blocker. ß-blockers are also useful in the management of angina symptoms accompanied by a high heart rate, hypertension (with or without a renin-angiotensin-aldosterone-system [RAS] blocker or CCB), or microvascular angina (with a RAS blocker and a statin). A ß-blocker is not suitable for a patient with low heart rate (<50 bpm), although use of a ß-blocker may be supported by a pacemaker if the ß-blocker is strongly indicated) and should be used at a low dose only in patients with low blood pressure.

The current position of ß-blockers in hypertension: guidelines and clinical practice.

The benefits of improved clinical outcomes through blood pressure (BP) reduction have been proven in multiple clinical trials and meta-analyses. The new (2023) guideline from the European Society of Hypertension (ESH) includes ß-blockers within five main classes of antihypertensive agents suitable for initiation of antihypertensive pharmacotherapy and for combination with other antihypertensive agents. This is in contrast to the 2018 edition of ESH guidelines that recommended ß-blockers for use primarily in patients with compelling indications such as cardiovascular comorbidities, e.g. coronary heart disease, heart failure. This change was based on the fact that the magnitude of BP reduction is the most important factor for adverse cardiovascular outcomes, over and above the precise manner in which reduced BP is achieved. The ESH guideline also supports the use of ß-blockers for patients with resting heart rate (>80 bpm); high resting heart rate is a sign of sympathetic overactivity, an important driver of adverse cardiac remodelling in the setting of hypertension and heart failure. Hypertension management guidelines support for the use of combination therapies for almost all patients with hypertension, ideally within a single-pill combination to optimise adherence to therapy. Where a ß-blocker is prescribed, the inclusion of a dihydropyridine calcium channel blocker within a combination regimen is rational. These agents together reduce both peripheral and central BP, which epidemiological studies have shown is important for reducing the burden of premature morbidity and mortality associated with uncontrolled hypertension, especially strokes.

Effect of Concomitant Drugs on Sodium Zirconium Cyclosilicate Hydrate in Artificial Intestinal Juice.

To explore drug interactions involving sodium zirconium cyclosilicate hydrate (SZC) and concomitant drugs like calcium antagonists (amlodipine and nifedipine) and ß-blockers (carvedilol and bisoprolol), we investigate how these concomitant drugs influenced the administration of SZC in an artificial intestinal juice. Initially, we assessed the potassium ion adsorption capacity, ranking it as follows: calcium polystyrene sulfonate (CPS, 54.9 mg/g) < sodium polystyrene sulfonate (SPS, 62.1 mg/g) < SZC (90.8 mg/g). However, the adsorption equilibrium was achieved in the order of CPS ≒ SPS (within 1 min) < SZC (within 1 h). Subsequently, we determined the residual percentages of amlodipine, nifedipine, carvedilol, and bisoprolol, finding them to be 79.0-91.9% for SZC, 0.38-38.4% for SPS, and 0.57-29.0% for CPS. These results suggest the efficacy of SZC in managing hyperkalemia alongside concomitant drugs in an artificial intestinal juice, with particular emphasis on amlodipine (calcium antagonist) and carvedilol (ß-blocker). Additionally, we identified the presence of carbon, nitrogen, and oxygen components from both drugs on the SZC surface following interaction. We also evaluated how amlodipine, nifedipine, carvedilol, and bisoprolol affected the administration of SZC in the presence of potassium ions. Our results indicate that potassium ions and concomitant drugs did not interfere with each other in the artificial intestinal juice. These results offer valuable insights into the administration of SZC in conjunction with concomitant drugs. Lastly, the presented data shows qualitative results in this study.

The Effect of ß-Blocker Eye Drops on Pulse Rate, Ocular Blood Flow, and Glaucoma Progression: A Retrospective Longitudinal Study.

INTRODUCTION: Our study was conducted to determine factors associated with the effectiveness of a ß-blocker eye drop add-on in altering pulse rate (PR) in glaucoma patients. METHODS: This retrospective study examined 236 eyes of 138 patients who received a ß-blocker eye drop add-on during follow-up. Patients were included if at least one PR measurement was available both before and after the add-on was started. We collected data on ophthalmic parameters: longitudinal PR; longitudinal choroidal blood flow, represented by laser speckle flowgraphy-measured mean blur rate (MBR); and diacron-reactive oxygen metabolites (d-ROMs). We used a multivariable linear mixed-effects model to investigate the effectiveness of the ß-blocker eye drop add-on in altering PR and examined factors contributing to a larger PR alteration after the add-on was started by analyzing the effect on PR of the interaction term between the add-on and clinical factors. We used the k-means method to classify the patients. RESULTS: The ß-blocker eye drop add-on reduced PR (- 7.61 bpm, P < 0.001). Female gender, higher PR when the add-on was started, lower central corneal thickness, and a higher d-ROM level were associated with greater reduction in PR (P < 0.05). In a cluster of patients with these clinical features, choroidal MBR increased by + 3.42% when we adjusted for change over time; MD slope, which represents the speed of glaucoma progression, improved by + 0.64 dB/year (P < 0.05). CONCLUSIONS: We identified a glaucoma subgroup in which PR decreased, choroidal blood flow increased, and glaucoma progression slowed after a ß-blocker eye drop add-on was started.

Association of ß-blocker use at discharge and prognosis of oldest old with acute myocardial infarction: a prospective cohort study.

PURPOSE: It is uncertain whether ß-blockers are beneficial for long-term prognosis in older patients following acute myocardial infarction (AMI). Thus, this study sought to examine the effect of ß-blockers on long-term cardiovascular mortality (CVM) in the oldest old (≥ 80 years) with AMI. METHODS: In this prospective, consecutive, non-randomized study, a total of 1156 patients with AMI admitted within 24 h after onset of symptoms were enrolled from January 2012 to February 2020. Univariate and multivariate Cox regression analyses were performed to examine the impact of ß-blocker use on prognosis. Furthermore, one-to-one propensity score matching (PSM) and inverse probability treatment weighting (IPTW) analyses were used to control for systemic differences between groups. The primary outcome was long-term CVM. RESULTS: Among the enrolled subjects, 972 (85.9%) were prescribed with ß-blockers at discharge. Over a mean follow-up of 26.3 months, 224 cardiovascular deaths were recorded. Both univariate [hazard ratio (HR), 1.41, 95% confidence interval (CI) 0.93-2.13] and multivariate (HR, 1.29, 95% CI 0.79-2.10) Cox regression analyses showed that ß-blocker use had no significant association with the long-term CVM, which was further demonstrated by PSM (HR, 1.31, 95% CI 0.75-2.28) and IPTW (HR, 1.41, 95% CI 0.73-2.69) analyses. Subgroup analyses according to sex, heart rate, hypertension, diabetes, revascularization, left ventricular ejection fraction, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers use showed consistent results as well. CONCLUSION: Our findings first suggested that the use of ß-blockers at discharge in oldest old with AMI was not useful for reducing post-discharge CVM, which need to be further verified by randomized controlled trials.

[Advances in the treatment of infantile hemangiomas of the larynx].

Infantile hemangiomas are relatively common soft tissue tumors in infants and young children, with a prevalence of about 4.5% in full-term newborns. Subglottic Hemangioma （SGH） is a relatively rare type of hemangioma, and its special location often causes respiratory distress and potentially life-threatening conditions in infants. Therefore, it is necessary for clinicians to make an accurate diagnosis and formulate a detailed treatment plan based on the clinical manifestations, the auxiliary examinations, the medical history and the vital signs evaluation of patients.This review describes the pathophysiological mechanism of infantile hemangioma and provides a detailed discussion on commonly used treatment methods in detail.

Association between the ß-blocker use and patients with sepsis: a cohort study.

Objective: This study aimed to assess whether ß-blockers are associated with mortality in patients with sepsis. Method: We conducted a retrospective cohort study of patients with sepsis using the Medical Information Market for Intensive Care (MIMIC)-IV and the emergency intensive care unit (eICU) databases. The primary outcome was the in-hospital mortality rate. The propensity score matching (PSM) method was adopted to reduce confounder bias. Subgroup and sensitivity analyses were performed to test the stability of the conclusions. Results: We included a total of 61,751 patients with sepsis, with an overall in-hospital mortality rate of 15.3% in MIMIC-IV and 13.6% in eICU. The inverse probability-weighting model showed that in-hospital mortality was significantly lower in the ß-blockers group than in the non-ß-blockers group [HR = 0.71, 95% CI: 0.66-0.75, p < 0.001 in MIMIC-IV, and HR = 0.48, 95% CI: 0.45-0.52, p < 0.001 in eICU]. In subgroups grouped according to sex, age, heart rate, APSIII, septic shock, and admission years, the results did not change. Conclusion: ß-blocker use is associated with lower in-hospital mortality in patients with sepsis, further randomized trials are required to confirm this association.

ß-blockers may be detrimental in frail patients with heart failure with preserved ejection fraction.

BACKGROUND: The effectiveness of ß-blocker in patients with heart failure with preserved ejection fraction (HFpEF) remains to be determined. We aimed to clarify the association between the use of ß-blocker and prognosis according to the status of frailty. METHODS: We compared prognosis between HFpEF patients with and without ß-blockers stratified with the Clinical Frailty Scale (CFS), using data from the PURSUIT-HFpEF registry (UMIN000021831). RESULTS: Among 1159 patients enrolled in the analysis (median age, 81.4 years; male, 44.7%), 580 patients were CFS ≤ 3, while 579 were CFS ≥ 4. Use of ß-blockers was associated with a worse composite endpoint of all-cause death and heart failure readmission in patients with CFS ≥ 4 (adjusted hazard ratio (HR) 1.43, 95% CI 1.10-1.85, p = 0.007), but was not significantly associated with this endpoint in those with CFS ≤ 3 (adjusted HR 0.95, 95% CI 0.71-1.26, p = 0.719) in multivariable Cox proportional hazard models. These results were confirmed in a propensity-matched analysis (HR in those with CFS ≥ 4: 1.42, 95% CI 1.05-1.90, p = 0.020; that in those with CFS ≤ 3: 0.83, 95% CI 0.60-1.14, p = 0.249), and in an analysis in which patients were divided into CFS ≤ 4 and CFS ≥ 5. CONCLUSIONS: Use of ß-blockers was significantly associated with worse prognosis specifically in patients with HFpEF and high CFS, but not in those with low CFS. Use of ß-blockers in HFpEF patients with frailty may need careful attention.

Influence of Different Types of ß-Blockers on Mortality in Patients on Hemodialysis.

Previous results regarding the association between types of ß-blockers and outcomes in patients on hemodialysis (HD) were inconsistent. Our study aimed to evaluate patient survival according to the type of ß-blockers administered using a large sample of patients with maintenance HD. Our study included patients on maintenance HD patients from a national HD quality assessment program (n = 54,132). We divided included patients into four groups based on their use and type; Group 1 included patients without a prescription of ß-blockers, Group 2 included patients with a prescription of dialyzable and cardioselective ß-blockers, Group 3 included patients with a prescription of non-dialyzable and non-cardioselective ß-blockers, and Group 4 included patients with prescription of non-dialyzable and cardioselective ß-blockers. The number of patients in Groups 1, 2, 3, and 4 were 34,514, 2789, 15,808, and 1021, respectively. The 5-year survival rates in Groups 1, 2, 3, and 4 were 69.3%, 66.0%, 68.8%, and 69.2%, respectively. Univariate Cox regression analyses showed the hazard ratios to be 1.10 (95% CI, 1.04-1.17) in Group 2 and 1.05 (95% CI, 1.02-1.09) in Group 3 compared to Group 1. However, multivariate Cox regression analyses did not show statistical significance among the four groups. Our study showed that there was no significant difference in patient survival based on the use or types of ß-blockers.

Different effects of medications for hypertension on renal function between patients with and without diabetes mellitus undergoing percutaneous coronary intervention: a retrospective single-center cohort study.

BACKGROUND: Diabetes mellitus (DM) and hypertension are well-known atherosclerosis risk factors. Furthermore, renal dysfunction is a crucial risk factor for patients with coronary artery disease (CAD), and managing renal function in these patients is complicated because of comorbid conditions and potential side effects during treatment. Therefore, this study aimed to investigate the effect of medications for hypertension on renal function after percutaneous coronary intervention (PCI) between patients with and without DM with statins. METHODS: In 297 consecutive patients undergoing PCI for stable angina pectoris, cystatin C (CysC) was evaluated at baseline and 9 months after PCI, and the percent change in CysC (%CysC) was calculated. The association of worsening renal function (WRF: %CysC ≥ 0) and baseline characteristics, including medications, was assessed. RESULTS: Among 297 hypertensive patients with statins, 196 and 101 were with and without DM, respectively. Angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker, and ß-blocker were prescribed in 56 (29%), 82 (42%), and 91 (46%) patients in the DM group, and 20 (20%), 52 (51%), and 52 (51%) in the non-DM group, respectively. The patients with WRF after PCI were 100 (51%) and 59 (58%) in the DM and non-DM groups (p = 0.261). Additionally, the %CysC had no significant differences between groups [median: 0%, interquartile range (IQR): -7.9% to 8.5% vs. median: 1.1%, IQR: -6.6% to 9.6%, p = 0.521]. Multivariate logistic analysis for WRF using relevant factors from univariate analysis showed that only ß-blocker [odds ratio (OR): 2.76, 95% confidence interval (CI): 1.03-7.90, p = 0.048] was independently associated with WRF in the DM group whereas ACEI (OR: 0.07, 95% CI: 0.01-0.47, p = 0.012) was negatively correlated with WRF in the non-DM group. CONCLUSION: The ß-blocker was the independent risk factor for WRF in patients with DM in the late phase after PCI for stable angina pectoris, while the use of ACEI had a renoprotective effect in patients without DM.

Case report: Right coronary artery to left ventricular fistula complicated with coronary artery dilation presenting as persistent cardiogenic ischemic chest pain.

We reported a patient with a fistula of the right coronary artery to the left ventricle, accompanied by dilation of the right coronary artery and persistent chest pain. This patient underwent surgical fistula closure surgery, but the fistula recurred. Persistent chest pain reappeared after encountering COVID-19 infection. We analyzed the mechanism of persistent myocardial ischemic chest pain caused by coronary artery fistula in this patient, the impact of surgery on the patient's disease, the possible mechanism of COVID-19 causing persistent ischemic chest pain in this patient, and the possible mechanism of metoprolol in alleviating myocardial ischemic chest pain in this patient.

Potential Interaction between Sodium Polystyrene Sulfonate and Prescription Drugs in Artificial Intestinal Juice.

This study evaluated the interaction between sodium polystyrene sulfonate (SPS) and several commonly used concomitant drugs, such as carvedilol, bisoprolol, imidapril, atorvastatin and azilsartan. The residual rate of adsorption 6 h after starting the experiment followed the order carvedilol (0.36%) < bisoprolol (19.7%) < imidapril (81.2%) < atorvastatin (86.5%) < azilsartan (87.9%) in artificial intestinal juice (pH 6.8). In addition, the pKa of carvedilol and bisoprolol was 8.0 and 9.6 and that of atorvastatin, azilsartan, and imidapril was 4.5, 6.1, and 2.4, respectively. These results indicate that the form (ionic or uncharged) of each drug is important to its reaction with SPS. Moreover, we demonstrated the effect of potassium ions (concentration of 1000 or 2000 mg/L) on the adsorption of concomitant drugs onto SPS in artificial intestinal juice. Our results show that the residual rate of adsorption of carvedilol and bisoprolol increases with increasing concentration of potassium ions whereas adsorption of potassium ions onto SPS was unaffected by carvedilol and bisoprolol under our experimental conditions. Finally, the obtained results revealed that interactions between SPS and carvedilol or bisoprolol readily occur in artificial intestinal juice.

Persistence of the carteolol hydrochloride/latanoprost fixed-combination ophthalmic solution, compared with the other ß-blocker/prostanoid FP receptor agonist fixed-combination ophthalmic solutions.

PURPOSE: To investigate the treatment persistence of carteolol hydrochloride/latanoprost fixed-combination ophthalmic solution (CAR/LAT) and other ß-blocker/prostanoid FP receptor agonist fixed-combination ophthalmic solutions (BB/FP) in the treatment of glaucoma. STUDY DESIGN: Retrospective observational cohort study. METHODS: A retrospective observational cohort study using JMDC Claims Database. Patients aged 20 years or older diagnosed with glaucoma between February 1, 2017, and March 31, 2020, and prescribed CAR/LAT or another BB/FP were included. RESULTS: A total of 16,612 patients (7423 in the CAR/LAT group and 9189 in the other BB/FP group) were included. The cumulative treatment persistence rate at the end of follow-up was 42.0% (64.9% at 1 year, 53.4% at 2 years, 45.0% at 3 years, and 42.0% at 4 years) in the CAR/LAT group and 34.7% (54.8% at 1 year, 43.6% at 2 years, 37.1% at 3 years, and 34.7% at 4 years) in the other BB/FP group. Treatment persistence was significantly longer in the CAR/LAT group compared to that in the other BB/FP group (hazard ratio 0.747, p < 0.0001). Over the treatment period, the number of patients who discontinued treatment was 3281 (44.2%) in the CAR/LAT group and 4926 (53.6%) in the other BB/FP group; the median duration of treatment was 135 days and 97 days, respectively. CONCLUSION: The study results suggest that persistence rates vary depending on the BB/FP and CAR/LAT appears to be more persistent than other BB/FP.

Pathophysiological Rationale and Clinical Evidence for Neurohormonal Modulation in Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome resulting from the interaction between cardiac diseases, comorbidities and ageing. HFpEF is characterised by the activation of neurohormonal axes, namely of the renin-angiotensin-aldosterone system and the sympathetic nervous system, although to a lesser extent compared with heart failure with reduced ejection fraction. This provides a rationale for neurohormonal modulation as a therapeutic approach for HFpEF. Nonetheless, randomised clinical trials have failed to demonstrate a prognostic benefit from neurohormonal modulation therapies in HFpEF, with the sole exception of patients with left ventricular ejection fraction in the lower range of normality, for whom the American guidelines suggest that such therapies may be considered. In this review, the pathophysiological rationale for neurohormonal modulation in HFpEF is summarised and the clinical evidence on pharmacological and nonpharmacological approaches backing current recommendations discussed.

In vitro and in silico study on the effect of carvedilol and sorafenib alone and in combination on the growth and inflammatory response of melanoma cells.

Melanoma is an aggressive skin cancer. Increasing evidence has shown the role of ß-adrenergic receptors in the pathogenesis of melanoma. Carvedilol is a widely used non-selective ß-AR antagonist with potential anticancer activity. The purpose of the study was to estimate the influence of carvedilol and sorafenib alone and in combination on the growth and inflammatory response of C32 and A2058 melanoma cells. Furthermore, this study also aimed to predict the probable interaction of carvedilol and sorafenib when administered together. Predictive study of the interaction of carvedilol and sorafenib was performed using the ChemDIS-Mixture system. Carvedilol and sorafenib alone and in combination showed a growth inhibitory effect on cells. The greatest synergistic antiproliferative effect on both cell lines was observed at Car 5 µM combined with Sor 5 µM. Analysis in silico identified diseases, proteins, and metabolic pathways that can be affected by the interaction of carvedilol and sorafenib. The results obtained demonstrated that carvedilol and sorafenib modulated the secretion of IL-8 by IL-1ß-stimulated by melanoma cell lines but the use of a combination of both drugs did not intensify the effect. In summary, the results presented indicate that the combination of carvedilol and sorafenib may have a promising anticancer effect on melanoma cells.

Gold vs. Silver Colloidal Nanoparticle Films for Optimized SERS Detection of Propranolol and Electrochemical-SERS Analyses.

The increasing pollution of surface and groundwater bodies by pharmaceuticals is a general environmental problem requiring routine monitoring. Conventional analytical techniques used to quantify traces of pharmaceuticals are relatively expensive and generally demand long analysis times, associated with difficulties in performing field analyses. Propranolol, a widely used ß-blocker, is representative of an emerging class of pharmaceutical pollutants with a noticeable presence in the aquatic environment. In this context, we focused on developing an innovative, highly accessible analytical platform based on self-assembled metal colloidal nanoparticle films for the fast and sensitive detection of propranolol based on Surface Enhanced Raman Spectroscopy (SERS). The ideal nature of the metal used as the active SERS substrate was investigated by comparing silver and gold self-assembled colloidal nanoparticle films, and the improved enhancement observed on the gold substrate was discussed and supported by Density Functional Theory calculations, optical spectra analyses, and Finite-Difference Time-Domain simulations. Next, direct detection of propranolol at low concentrations was demonstrated, reaching the ppb regime. Finally, we showed that the self-assembled gold nanoparticle films could be successfully used as working electrodes in electrochemical-SERS analyses, opening the possibility of implementing them in a wide array of analytical applications and fundamental studies. This study reports for the first time a direct comparison between gold and silver nanoparticle films and, thus, contributes to a more rational design of nanoparticle-based SERS substrates for sensing applications.

Increased circulating phenylacetylglutamine concentration elevates the predictive value of cardiovascular event risk in heart failure patients.

BACKGROUND: Phenylacetylglutamine (PAGln)-a newly discovered microbial metabolite produced by phenylalanine metabolism-is reportedly associated with cardiovascular events via adrenergic receptors. Nonetheless, its association with cardiovascular outcomes in heart failure (HF) patients remains unknown. OBJECTIVES: This study aimed to prospectively investigate the prognostic value of PAGln for HF. METHODS: Plasma PAGln levels were quantified by liquid chromatography-tandem mass spectrometry. We first assessed the association between plasma PAGln levels and the incidence of adverse cardiovascular events in 3152 HF patients (including HF with preserved and reduced ejection fraction) over a median follow-up period of 2 years. The primary endpoint was the composite of cardiovascular death or heart transplantation. We then assessed the prognostic role of PAGln in addition to the classic biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP). The correlation between PAGln levels and ß-blocker use was also investigated. RESULTS: In total, 520 cardiovascular deaths or heart transplantations occurred in the HF cohort. Elevated PAGln levels were independently associated with a higher risk of the primary endpoint in a dose-response manner, regardless of HF subtype. Concurrent assessment of PAGln and NT-proBNP levels enhanced risk stratification among HF patients. PAGln further showed prognostic value at low NT-proBNP levels. Additionally, the interaction effects between PAGln and ß-blocker use were not significant. CONCLUSIONS: Plasma PAGln levels are an independent predictor of an increased risk of adverse cardiovascular events in HF. Our work could provide joint and complementary prognostic value to NT-proBNP levels in HF patients.

Oral Propranolol Therapy for Infantile Hemangioma: Long-term Follow-up.

ß-blocker therapy is currently the treatment of choice for infantile hemangiomas (IH), albeit with limited data on long-term treatment outcomes. Herein, authors treated 67 IH lesions in 47 patients with oral propranolol at 2 mg/kg/d for a median of 9 mo and followed them up for a median of 48 mo. While no maintenance therapy was required for 18 lesions (26.9%), the rest needed maintenance therapy. Both treatment regimens had comparable efficacy (83.3±23.9% and 92.0±13.8%) but chances of IH recurrence was higher in lesions requiring maintenance therapy. Also, patients treated at ≤5 mo of age had a significantly better response and a lower recurrence rate than patients treated at >5 mo of age (95.0±7.9% vs. 87.0±17.5%, p = 0.05). Authors' experience suggests that longer durations of maintenance therapy offered no added advantage to the overall improvement of IH while treatment initiation at an earlier age showed better improvement and lower recurrence rates.