Oral Beta-blockers Research Articles

CE-454610-3 VT STORM DUE TO HYPERTROPHIC CARDIOMYOPATHY TREATED WITH ALCOHOL SEPTAL ABLATION

Radiofrequency (RF) ablation is a guideline-recommended therapy for ventricular tachycardia (VT). However, certain locations can be inaccessible through endocardial or epicardial approach. There are several documented unconventional techniques in these cases where VT is either treatment-refractory to RF ablation, or ablation is unlikely to be successful due to deep intramural substrate. N/A N/A A 66-year-old gentleman with a history of coronary artery disease (CAD) presents with four days of palpitations and lightheadedness to the emergency department. An ECG was performed which showed monomorphic VT from a basal septal focus. He was hemodynamically stable and thus started on a lidocaine drip and intermittent metoprolol IV pushes with conversion to sinus rhythm. Given the history of CAD, primary differential concerns were ischemia-mediated or scar-mediated VT. Thus, the patient underwent a coronary angiogram which revealed stable non-obstructive CAD. The patient then underwent a cardiac MRI which revealed severe asymmetric left ventricular hypertrophy measuring up to 18 mm in the mid-basal interventricular septum with mid-myocardial late gadolinium enhancement in the same area. This was most consistent with hypertrophic cardiomyopathy (HCM) as the etiology for the patient’s VT. As the patient continued to have significant ventricular ectopy and recurrent bouts of sustained VT on medical management, options for VT ablation were discussed. Overall, given the deep intramural location of the suspected VT substrate, endocardial and epicardial approaches were thought to have a low probability of success. Transarterial coronary ethanol ablation (TCEA) of the septum was thought to have the highest likelihood of success at controlling the patient’s VT in the setting of HCM. The patient underwent successful TTE guided TCEA of the first septal branch. Left ventricular outflow tract (LVOT) gradient improved from 45 to 17 mmHg. The patient was observed for 24 hours without evidence of VT. An ICD was subsequently implanted for secondary prevention. The patient was discharged in stable condition on an oral beta blocker without any additional anti-arrhythmic medications. In patients with VT due to HCM where there is a deep intramural substrate not amenable to traditional RF catheter ablation, TCEA is a reasonable approach. We describe a case of successful TCEA in both decreasing a patient’s LVOT gradient as well as cessation of the patient’s treatment refractory VT.

A Comparative Study to Investigate the Effects of Bisoprolol in Patients with Chronic Heart Failure and Hypertension When Switched from Tablets to Transdermal Patches.

Oral beta-blockers are effective for heart failure and hypertension. Here, we conducted a prospective study to investigate the efficacy of the beta-blocker bisoprolol in patients switching from the oral tablet to the transdermal patch. We studied 50 outpatients receiving oral bisoprolol for chronic heart failure and hypertension. After patients switched treatments, we measured heart rate (HR) over 24 h by Holter echocardiography as the primary endpoint. Secondary endpoints were (1) HR at 00:00, 06:00, 12:00, and 18:00, (2) the total number of premature atrial contractions (PACs) over 24 h and the incidence rate per time segment, and the total number of premature ventricular contractions (PVCs) over 24 h and the incidence rate per time segment, (3) blood pressure, (4) atrial natriuretic peptide and B-type natriuretic peptide, and (5) echocardiography. Minimum, maximum, mean, and total HR over 24 h was not significantly different between the two groups. Mean and maximum HR at 06:00, total PACs, total PVCs, and PVCs at 00:00 to 05:59 and 06:00 to 11:59 were significantly lower in the patch group. Compared with oral bisoprolol, the bisoprolol transdermal patch lowers HR at 06:00 and inhibits the onset of PVCs during sleep and in the morning.

631 Computerized two-dimensional planimetry: Application on efficacy evaluation of topical beta blocker versus topical plus oral beta-blocker for infantile hemangioma

631 Computerized two-dimensional planimetry: Application on efficacy evaluation of topical beta blocker versus topical plus oral beta-blocker for infantile hemangioma

Engineered exosomes for targeted delivery of miR-187-3p suppress the viability of hemangioma stem cells by targeting Notch signaling.

BackgroundInfantile hemangioma (IH) is the most common benign vascular tumor of infancy and is proposed to arise from hemangioma stem cells (HemSCs). Therapies for IH include oral beta-blockers, surgery, and the delivery of novel therapeutic agents, such as bioactive microRNAs (miRNAs). However, in the extracellular environment, miRNA is easily hydrolyzed by RNase. miR-187-3p has previously been confirmed to promote or inhibit various malignancies, but its role in the development and progression of IH remains unclear.MethodsIn this study, engineered exosomes (E-exos) were exploited to deliver miR-187-3p into HemSCs. The E-exos were generated by introducing miR-187-3p mimics into human adipose mesenchymal stem cell-derived exosomes (hAMSC-exos) via electroporation. The expression and secretion of miR-187-3p were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot analysis, transmission electron microscopy (TEM), and dynamic light scattering (DLS) were used to characterize the exosomes. The effects of the E-exos on HemSC viability were examined using the tube formation assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Western blot analysis was used to evaluate the effects of E-exos on Notch-1, Notch-4, and Jagged-1 expression in HemSCs.ResultsE-exos did not differ significantly from hAMSC-exos in terms of morphology, particle size, or surface markers. E-exos could be internalized by HemSCs, and the course of cellular uptake of E-exos was time dependent. After 12 hours of treatment, E-exos significant inhibited tube formation. Notch signaling was also inhibited by miR-187-3p loading by E-exos. E-exos showed excellent inhibitory effects against HemSC proliferation via Notch signaling.ConclusionsThis study provides a foundation for using hAMSC-exos to optimize current clinical options to facilitate IH treatment and deliver therapeutic agents in the future.

Impaired heart rate variability triangular index predicts stroke and systemic embolism in patients with atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation Introduction Despite the broad use of oral anticoagulants, stroke remains one of the most serious complications in atrial fibrillation (AF) patients. Stroke has been linked to disturbances of the autonomic nervous system as both share similar risk factors. Therefore, impaired cardiac autonomic function may indicate an enhanced stroke risk. Purpose We hypothesized that impaired cardiac autonomic function, quantified by means of heart rate variability (HRV), might be useful in predicting stroke in patients with AF. Methods We enrolled 1,933 patients with a documented history of AF from the multicenter Swiss-AF cohort study who were either in sinus rhythm (SR-group, n=1130) or AF (AF-group, n=803) on a 5-minute resting ECG recording. HRV triangular index (HRVI), standard deviation of normal-to-normal intervals, root mean square root of successive differences of normal-to-normal intervals, mean heart rate, 5-min total power and power in the high frequency, low frequency and very low frequency range were calculated. We constructed cox regression models to analyze the predictive power of HRV parameters for the composite endpoint stroke or systemic embolism. Results Mean age was 71±8 years in the SR group and 75±8 in the AF group, 28% of the total study cohort were female. 36 patients in the SR group (3.2%) and 58 patients in the AF group (6.5%) experienced a stroke or systemic embolism during a follow-up time of 4.0±1.3 years. In patients with sinus rhythm, HRVI <15 was the only HRV parameter independently associated with stroke or systemic embolism (hazard ratio 2.94; 95% confidence interval 1.3-6.8; p=0.011) after adjustment for multiple clinical confounders (age, sex, AF type, history of hypertension, history of diabetes, history of chronic kidney disease, prior stroke or transient ischemic attack, intake of oral anticoagulation, antiarrhythmics or betablockers). In the AF group, no HRV parameter was associated with the composite endpoint. Conclusions HRVI measured during SR on a single 5-minute ECG recording is an independent predictor of stroke or systemic embolism in AF patients. HRV analysis may help to improve risk stratification in AF patients.

Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD): a randomised controlled trial (BICS)

BackgroundChronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta blocker use in people with COPD is associated with a reduced risk of COPD exacerbations. The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease.MethodsBICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV1 < 80% predicted, FEV1/FVC < 0.7), a self-reported history of ≥ 2 exacerbations requiring treatment with antibiotics and/or oral corticosteroids in a 12-month period since March 2019, age ≥ 40 years and a smoking history ≥ 10 pack years. A computerised randomisation system will allocate 1574 participants with equal probability to intervention or control groups, stratified by centre and recruitment in primary/secondary care. The intervention is bisoprolol (1.25 mg tablets) or identical placebo. The dose of bisoprolol/placebo is titrated up to a maximum of 4 tablets a day (5 mg bisoprolol) over 4–7 weeks depending on tolerance to up-dosing of bisoprolol/placebo—these titration assessments are completed by telephone or video call. Participants complete the remainder of the 52-week treatment period on the final titrated dose (1, 2, 3, 4 tablets) and during that time are followed up at 26 and 52 weeks by telephone or video call. The primary outcome is the total number of participant reported COPD exacerbations requiring oral corticosteroids and/or antibiotics during the 52-week treatment period. A sub-study will risk stratify participants for heart failure by echocardiography and measurement of blood biomarkers.DiscussionThe demonstration that bisoprolol reduces the incidence of exacerbations would be relevant not only to patients and clinicians but also to healthcare providers, in the UK and globally.Trial registrationCurrent controlled trials ISRCTN10497306. Registered on 16 August 2018

Long-Term Beta-Blocker Therapy After Myocardial Infarction Without Heart Failure in the Reperfusion Era-Systemic Review and Meta-analysis.

Beta-blockers are recommended as a standard treatment for patients who experience a myocardial infarction (MI). However, the evidence supporting this recommendation is based on the prereperfusion era data. This review aims to evaluate the effectiveness of long-term (≥1 year) beta-blocker therapy in post-MI patients without clinical heart failure (HF) in the reperfusion era. We included observational cohort studies, which compared at least 1 year use of beta-blockers to no beta-blockers in patients with an acute MI, but without HF. The clinical endpoint considered was all-cause mortality, except for cardiovascular death in one study. Five cohort studies and 217,532 patients were included. One study demonstrated a reduction in all-cause mortality with beta-blockers, whereas, in 4 studies, there was no difference in the death rate. The pooled estimate by random effect showed that beta-blocker treatment does not reduce mortality (odds ratio 0.800, 95% confidence interval 0.559-1.145) with high heterogeneity (I2 = 94%). This meta-analysis shows that the use of oral beta-blockers for 1 year or more does not reduce the mortality of MI patients without HF. Large randomized trials need to evaluate beta-blocker discontinuation after an acute MI.

Infantile Hemangioma: A Current Review.

Infantile hemangiomas (IHs) are common vascular lesions which are benign but can cause significant functional and cosmetic morbidity. Since the fortuitous discovery of propranolol being effective to treat IH over a decade ago, the therapy and prognosis for children with IH have improved dramatically. Oral propranolol (as well as other oral beta-blockers and topical timolol) are safe and effective treatments, and have now supplanted other therapies. Making the correct diagnosis is crucial, because other vascular lesions can mimic IH. In addition, IH can be the first manifestation of an underlying syndrome. For IH requiring treatment, initiating treatment early is key to optimizing success. Therefore, early recognition and referral, if necessary, are important. Continued research on IH, both basic science and clinical, should result in continued advances.

Clinical features, risk factors and a prediction model for in-hospital mortality among diabetic patients infected with COVID-19: data from a referral centre in Iran

ObjectivesThe aim of this study was to identify risk factors of in-hospital mortality among diabetic patients infected with COVID-19. Study designThis is a retrospective cohort study. MethodsUsing logistic regression analysis, the independent association of potential prognostic factors and COVID-19 in-hospital mortality was investigated in three models. Model 1 included demographic data and patient history; model 2 consisted of model 1, plus vital signs and pulse oximetry measurements at hospital admission; and model 3 included model 2, plus laboratory test results at hospital admission. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported for each predictor in the different models. Moreover, to examine the discriminatory powers of the models, a corrected area under the receiver-operating characteristic curve (AUC) was calculated. ResultsAmong 560 patients with diabetes (men = 291) who were hospitalised for COVID-19, the mean age of the study population was 61.8 (standard deviation [SD] 13.4) years. During a median length of hospitalisation of 6 days, 165 deaths (men = 93) were recorded. In model 1, age and a history of cognitive impairment were associated with higher mortality; however, taking statins, oral antidiabetic drugs and beta-blockers was associated with a lower risk of mortality (AUC = 0.76). In model 2, adding the data for respiratory rate (OR 1.07 [95% CI 1.00–1.14]) and oxygen saturation (OR 0.95 [95% CI 0.92–0.98]) slightly increased the AUC to 0.80. In model 3, the data for platelet count (OR 0.99 [95% CI 0.99–1.00]), lactate dehydrogenase (OR 1.002 [95% CI 1.001–1.003]), potassium (OR 2.02 [95% CI 1.33–3.08]) and fasting plasma glucose (OR 1.04 [95% CI 1.02–1.07]) significantly improved the discriminatory power of the model to AUC 0.86 (95% CI 0.83–0.90). ConclusionsAmong patients with type 2 diabetes, a combination of past medical and drug history and pulse oximetry data, with four non-expensive laboratory measures, was significantly associated with in-hospital COVID-19 mortality.

Discontinuation of beta-blockers among nursing home residents at end of life.

Given limited life expectancy of nursing home (NH) residents, harms of continuing beta-blockers (BBs) may outweigh clinical benefits. Our objective was to describe beta-blocker discontinuation for NH residents during the last year of life, and identify characteristics associated with earlier discontinuation. This was a retrospective cohort study that included all long-stay residents in fee-for-service Medicare who died in 2016 and were prescribed oral BBs 1 year before death. Beta-blocker discontinuation was defined as a gap in medication on hand for ≥45 days per Medicare Part D claims, measured from the last date drug was on hand. Comorbidities were obtained from Chronic Condition Warehouse, and other characteristics from the Minimum Data Set. Kaplan-Meier curves were used to describe time to first discontinuation. Findings were stratified by cardiac diagnoses, perceived life expectancy of <6months, or elevated mortality index. Eighty-eight thousand two hundred and eighty-four residents were prescribed ≥1 daily BB 12 months before death. Mean age was 84.1 years and 69.2% were female. Of these, 60,573 residents (68.6%) remained on a BB in the last 45 days of life, and 57,880 residents (65.6%) had ≥1 cardiac diagnosis. Only 5239 residents (5.9%) had elevated mortality index, whereas 16,798 residents (19.0%) had perceived poor prognosis. In the last year of life, there was no difference in beta-blocker discontinuation pattern between residents with and without cardiac diagnoses. Residents with perceived poor prognosis and elevated mortality index discontinued BBs earlier. For example, mean time until discontinuation among residents with poor perceived prognosis was 245 versus 279 days in residents without such prognosis (p < 0.0001). BBs are commonly prescribed to NH residents in the final year of life. Overall, discontinuation occurs earlier in residents for whom clinicians perceive limited life expectancy, suggesting that improved prognostication may offer an important opportunity to reduce polypharmacy toward end of life.

The Effect of Intravenous and Oral Beta-Blocker Use in Patients with Type B Thoracic Aortic Dissection

Beta-blockers have become the cornerstone for medical management in patients with chronic type B aortic dissection (TBAD). However, the effect of being on and/or receiving intravenous beta-blockers during hospitalization on outcomes of surgical repair of TBAD is not fully described. We sought to investigate this association during open surgical repair (OSR) and endovascular (Endo) intervention for nontraumatic TBAD. The Premier Healthcare Database was inquired (June/2009-March/2015). Patients with nontraumatic isolated TBAD were identified via ICD-9-CM diagnosis and procedural codes. Patients with codes that indicated TAAD were excluded. In-hospital mortality, cardiac complications (CHF, MI, arrythmia) and stroke were evaluated. Log binomial regression analyses with bootstrapping were performed to assess the relative risk of adverse outcomes. A total of 1,752 were admitted for OSR (54.3%) and Endo (45.7%) TBAD repair. Use of oral beta blocker (BB) was 16.0% in OSR and 56.4% in Endo groups. In each arm, patients on BB were more likely to be diabetic, on aspirin or statin and more likely to receive additional IV BB than nonBB patients. There was no significant difference in age, sex, race, or prior history of CHF between BB and nonBB groups. Mortality was proportionally lower in patients on BB in OSR group (7.9% vs. 16.7%; P=0.006) and Endo (3.3% vs. 9.2%; P < 0.001). The adjusted relative risk for mortality and stroke were significantly lower in oral BB recipients compared with none [aRR (95% CI): 0.53 (0.32-0.90) and 0.46 (0.25-0.87); both P ≤ 0.02]. IV metoprolol was the only IV BB that reduced mortality [aRR (95% CI): 0.62 (0.46-0.85); P=0.003]. A dose of ≤10 mg was associated with significant mortality reduction: 6.3% (3.0-9.5%) compared with 8.1% (4.6-11.6%) in no IV BB group. Cardiac complications were not affected by BB use. For patients with nontraumatic TBAD, use of oral BB was associated with significant protection against in-hospital mortality and stroke following repair. Metoprolol was the only Intravenous BB type associated with improved survival. Further research is warranted to elucidate the effect of beta-blockers on the long-term surgical outcomes of TBAD.

Association of beta-blockers or inhibitors of renin-angiotensin system with clinical outcomes in patients with mid-range left ventricular ejection fraction after acute myocardial infarction

Abstract Background In the era of the initial optimal interventional and medical therapy for acute myocardial infarction (AMI), a number of patients with mid-range left ventricular ejection fraction (EF) (&amp;gt;40%, &amp;lt;50%) becomes increasing. Purpose This observational study aimed to investigate the association between oral beta-blockers or inhibitors of renin-angiotensin system (RAS) and 2-year clinical outcomes in patients with mid-range EF after AMI. Methods Among 13,624 patients enrolled in the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), propensity-score matched patients who survived the initial attack and had mid-range EF were selected according to beta-blocker or RAS inhibitor therapy at discharge. Results Beta-blocker therapy at discharge was associated with lower 2-year major adverse cardiac events (MACE) of cardiac death, MI, revascularization or re-hospitalization due to heart failure (8.7 vs. 12.8/100 person-year; hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.50–0.93; P=0.015), and no significant interaction between EF ≤45% and &amp;gt;45% was observed (P for interaction=0.354). This association was mainly driven by lower MI in patients with beta-blockers (1.6 vs. 3.1/100 person-year; HR 0.50; 95% CI 0.26–0.95; P=0.035). Inhibitors of RAS at discharge were not associated with lower 2-year MACE, but with lower re-hospitalization due to heart failure (1.8 vs. 3.5/100 person-year; HR 0.53; 95% CI 0.33–0.86; P=0.010) without significant interaction between EF ≤45% and &amp;gt;45% (P for interaction=0.333). Conclusions Beta-blockers or RAS inhibitors at discharge were associated with better 2-year clinical outcomes without significant interaction between ≤45% and &amp;gt;45% in patients with mid-range EF after AMI.&amp;lt;/ef&amp;lt;50%)&amp;gt; Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Korea Centers for Disease Control and Prevention. 2-year clinical outcomes

Compound heterozygote KCNQ1 mutation causing Jervell Lange Neilson syndrome: a case report of genotype-phenotype correlation

Congenital sensorineural hearing loss (SNHL) is a common phenomenon with several genetic and non-genetic associations that require early diagnosis and work-up to prompt appropriate interventions. Of the genetic associations, Jervell and Lange-Nielsen syndrome (JLNS) remains a rare monogenic disease that is characterized by SNHL, prolongation of QT interval, syncopal attacks due to ventricular arrhythmias and sudden cardiac death from very early in life. We hereby report a 5 years old girl with SNHL and recurrent blackout episodes in early childhood with significant family history, admitted for cochlear implant who developed ventricular arrhythmias requiring multiple interventions with further investigations revealing a prolonged QT interval on electrocardiography (ECG) with metabolic abnormalities (hypomagnesemia and hypokalemia). Her clinical exome study showed a compound heterozygous KCNQ1 mutation, a more sporadic form of JLNS managed using oral beta-blocker. This experience illustrates the relevance of a detailed systemic evaluation with an elaborate cardiac assessment in children with SNHL, more so in the presence of frequent unexplained acute life-threatening episodes.

Characteristics and management of heart failure: a retrospective single center study in Cambodia

Abstract Funding Acknowledgements Type of funding sources: None. Background The most common etiologies of cardiovascular disease (CVD) in Cambodia included heart failure (HF) (52.9%), angina pectoris (11.6%), and acute myocardial infarction (4.11%). Purpose The goal of this study is to describe characteristics, clinical features, evaluation and treatment of patients with HF admitted to one public hospital in Cambodia. Methods This retrospective study included all patients age ≥18 years who were admitted with the diagnosis of HF to the Intensive Care Unit of one public hospital from 1st January 2017 to 31st December 2018. Out of 140 cases, 20 were excluded because they did not meet the inclusion criteria. Characteristics, evaluation, and treatment of the 120 remaining patients were analyzed. Results HF with reduced Ejection Fraction (HFrEF) was present in 15%, with mid-range EF (HFmrEF) in 13.3%, and preserved EF (HFpEF) in 71.7% of patients. Hypertension was more prevalent in HFpEF (89.5%, P &amp;lt;0.001) (table 1). Diabetes was more common in HFpEF and HFmrEF (52.3% and 43.7%, P = 0.316) (table 1). Coronary artery disease was more prevalent in HFrEF (72.2%, P = 0.015) (table 1). Global wall hypokinesia was more common in HFrEF group (72.2%, P &amp;lt;0.001) (figure 1). Patients with HFrEF who were given ACEi/ARB (44.4%, P = 0.324) was lower than those with HFpEF (55.8%, P = 0.324). Oral beta-blockers were commonly used in HFrEF (44.4%, P &amp;lt;0.175). Spironolactone was prescribed more in HFmrEF (56.2%, P &amp;lt;0.001) patients than in those with HFrEF (44.4%, P &amp;lt;0.001). Conclusions HFpEF was the most common types of HF in this population, and was associated with hypertension and diabetes. HFrEF was least common and was associated with CAD. Prevention and treatment of hypertension and diabetes is essential to reduce the incidence of HFpEF while greater use of guideline recommended drugs is needed in HFrEF. TABLE 1: Characteristics of HF Patients Clinical characteristics Total (n = 120) HFrEF (n = 18) HFmrEF (n = 16) HFpEF (n = 86) p value Age (years) 58.8 ± 15.2 57.2 ± 16.3 57.3 ± 16.3 61.8 ± 12.9 0.274 Women, n (%) 57 (47.5) 10 (55.5) 4 (25.0) 43 (50.0) 0.14 Men, n (%) 63 (52.5) 8 (44.4) 12 (75.0) 43 (50.0) 0.14 Hypertension, n (%) 95 (79.2) 7 (38.9) 11 (68.7) 77 (89.5) &amp;lt;0.001 Diabetes, n (%) 58 (48.3) 6 (33.3) 7 (43.7) 45 (52.3) 0.316 CAD, n (%) 55 (45.8) 13 (72.2) 9 (56.2) 32 (37.2) 0.015 Values are shown as n (%) or mean ± SD. HFrEF, heart failure with reduced ejection fraction; HFmrEF, heart failure with mid-range ejection fraction; HFpEF, heart failure with preserved ejection fraction; CAD, coronary artery disease. Abstract FIGURE 1: Proportion of HF and LVWM

Inotropes in Chronic Beta-Blocker Therapy

The increasing rate of cardiovascular disorders contributes to rising hospitalized patients receive chronic oral beta-blocker therapy. Beta-blockers remain one of the fundamental therapy for chronic heart failure. Still, their role in decompensated heart failure and severe sepsis during hospitalization is often debated and inconsistent in clinical practice. In recent years, evidence of the efficacy and clinical outcomes of beta-blockers in acute heart failure (AHF) have accumulated. Clinical research indicates that chronic beta-blockade withdrawals should be prevented, or as soon as hemodynamic stabilization and euvolemic condition are reached, it should be reinstituted. As a subset of AHF patients with low cardiac output required inotropes, the choice of proper agent is fundamental. Different inotropic agents such as inhibitors of the phosphodiesterase, levosimendan, and dobutamine also their associations with beta-blockers are discussed.

Paediatrics: how to manage infantile haemangioma.

Infantile haemangiomas (IHs) are relatively common benign vascular tumours found in the paediatric population. They have varying sizes and involve different depths in the skin leading to various colours, shapes and textures. Although considered harmless in most cases, they may lead to life-threatening complications or cause permanent disfigurations and organ dysfunction. For problematic IHs, the treatment options include oral and topical beta-blockers, systemic corticosteroids, laser treatment, and surgery. In this narrative review, the treatment options for problematic IH are compared and delivered concisely to facilitate the clinical decisions from practitioners, including those in primary care settings. Oral propranolol is currently considered the first-line intervention for problematic IHs. For superficial lesions, there is robust evidence for the use of topical timolol maleate. Systemic corticosteroids are sometimes used in specific situations such as resistance or contraindications to beta-blockers. Surgical excision can be considered in cases requiring urgent intervention such as airway obstruction; this can be done alongside laser therapies for the removal of residual tissue or when reconstructing areas of deformity. The combination of multiple treatment modalities may lead to a more rapid clinical response.

CLINICAL EFFECTS OF BETA-BLOCKERS IN HYPERTENSIVE PATIENTS WITH ACUTE MYOCARDIAL INFARCTION AFTER ONE YEAR

Objective: Although the oral beta-blocker therapy is recommended at least 3 years after acute myocardial infarction (AMI), especially in hypertensive patients to control blood pressure, the evidence to support its clinical benefit is very poor. This study aimed to investigate the long-term clinical effects of beta-blockers in hypertensive patients with AMI who had no major adverse cardiac events (MACE) until 1 year after the initial attack. Design and method: Among 13,624 patients who were enrolled in nationwide AMI database of South Korea, the KAMIR-NIH Registry, 4,610 hypertensive patients, who underwent echocardiographic study and had no MACE (a composite of cardiac death, MI, revascularization or readmission due to heart failure) until 1 year, were selected in this study. Results: Beta-blockers were prescribed in 4,237 hypertensive patients (92%) at 1 year after AMI. On multivariable Cox-proportional hazard analysis, beta-blockers further reduced 1-year cardiac death (1.4 vs. 7.5/100 person-year; HR 0.23; 95% CI 0.14–0.38; p &lt; 0.001), MI (1.1 vs. 3.1/100 person-year; HR 0.33; 95% CI 0.16–0.68; p = 0.002), and MACE (5.8 vs. 11.1/100 person-year; HR 0.54; 95% CI 0.37–0.79; p = 0.001). However, clinical outcomes showed a significant interaction with left ventricular ejection fraction (LVEF). Beta-blockers decreased 1-year MACE of patients with LVEF =&lt;40% (11.3 vs. 24.5/100 person-year; HR 0.40; 95% CI 0.19–0.84; p = 0.015) and 40% &lt;LVEF &lt;50% (6.3 vs. 18.9/100 person-year; HR 0.43; 95% CI 0.22–0.85; p = 0.015, but not those with LVEF &gt;=50% (4.7 vs. 5.8/100 person-year; HR 0.77; 95% CI 0.42–1.43; p = 0.411). ∗HR; hazard ratio, CI; confidence interval. Conclusions: Beta-blockers improved the clinical outcomes in hypertensive patients with mid-range as well as reduced LVEF until 2 years after AMI. However, its benefit in hypertensive patients with preserved LVEF was questionable.

Efficacy of Long-Term Oral Beta-Blocker Therapy in Patients Who Underwent Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction With Preserved Left Ventricular Ejection Fraction: A Systematic Review and Meta-analysis.

After the results of the first multicenter, prospective randomized clinical trial (RCT) evaluating long-term efficacy of oral beta-blockers in patients with preserved left ventricular ejection fraction (LVEF) after ST elevation myocardial infarction (STEMI), we decided to conduct an updated systematic review and meta-analysis to evaluate the long-term efficacy of oral beta-blocker use in patients with preserved LVEF who underwent percutaneous coronary intervention (PCI) for STEMI. A time-limited search from January 1, 1999, to April 16, 2020, on PubMed and EMBASE was conducted on April 16, 2020, for observational studies and clinical trials evaluating the efficacy of long-term oral beta-blockers in patients with preserved LVEF after STEMI treated with PCI. The comparative outcomes between beta-blockers and non-beta-blockers were assessed by pooling weighted odds ratio (OR) with 95% confidence interval (CI) using random-effects model. The outcomes of interest were all-cause mortality and major adverse cardiac event (MACE). Twelve studies (11 observational and 1 RCT) comprising 32,108 patients (19,740 on beta-blocker therapy and 12,368 without beta-blocker therapy) were included. Of which, 75% percent were male (mean age of 64 years: 63.87 ± 3.01 years on beta-blocker therapy and 64.76 ± 3.02 years on non-beta-blocker therapy; P = 0.129) with a follow-up of up to 4.7 years. Unadjusted all-cause mortality [OR = 0.58 (95% CI: 0.42-0.79)] and adjusted all-cause mortality [OR = 0.64 (95% CI: 0.48-0.87)] were significantly lower in patients on the long-term beta-blocker therapy group. However, unadjusted MACE [OR = 0.87 (95% CI: 0.70-1.08)] was not reduced with beta-blocker therapy in these patients. Patients with preserved LVEF after STEMI treated with PCI on long-term oral beta-blocker therapy have a significant reduction in risk of all-cause mortality, without an effect on MACE rates. The only RCT included showed neutral effect, so results of ongoing RCTs are anticipated. Considering that the only high-quality data (RCT) suggest a neutral effect, one should be cautious in interpreting the conclusion.

News on infantile haemangioma. Part 1: clinical course and pathomechanism.

Currently, there is no doubt that the first choice of treatment for alarming infantile haemangiomas (IHs) is oral beta-blockers. However, research in this field remains active, as the pathogenesis of IH is still not completely elucidated. Furthermore, there are different approaches to the management of IHs with beta-blockers. In Part 1 of this review we will discuss the state-of-the-art evidence for IH with regard to (i) the definition, epidemiology, course, risk factors and sequelae, and (ii) the pathogenesis, focusing on genetic studies. This review will update the reader on the latest developments in the pathogenesis of IH. Furthermore, we hope this review will give more insight into risk factors and sequelae of IH, thereby contributing to better decisions in the clinical management of patients with IH. The therapy and evaluation of IHs will be discussed in Part 2 of this review.

Impaired heart rate variability triangular index to identify clinically silent strokes in patients with atrial fibrillation

Abstract Introduction The identification of clinically silent strokes in patients with atrial fibrillation (AF) is of high clinical relevance as they have been linked to cognitive impairment. Overt strokes have been associated with disturbances of the autonomic nervous system. Purpose We therefore hypothesize that impaired heart rate variability (HRV) can identify AF patients with clinically silent strokes. Methods We enrolled 1358 patients with AF without a history of stroke or transient ischemic attack from the multicenter SWISS-AF cohort study who were in sinus rhythm (SR-group, n=816) or AF (AF-group, n=542) on a 5 minute resting ECG recording. HRV triangular index (HRVI), the standard deviation of normal-to-normal intervals (SDNN) and the mean heart rate (MHR) were calculated. Brain MRI was performed at baseline to assess the presence of large non-cortical or cortical infarcts, which were considered silent strokes without history of stroke or transient ischemic attack. We constructed binary logistic regression models to analyze the association between HRV parameters and silent strokes. Results At baseline, silent strokes were detected in 10.5% in the SR group and 19.9% in the AF group. In the SR-group, HRVI &amp;lt;15 was the only parameter independently associated with the presence of silent strokes (odds ratio (OR) 1.69; 95% confidence interval (CI): 1.04–2.72; p=0.033) after adjustment for various clinical covariates (age, sex, systolic blood pressure, history of hypertension, history of diabetes, history of heart failure, prior myocardial infarction, prior major bleeding, intake of oral anticoagulation, antiarrhythmics or betablockers). Similarly, in the AF-group, HRVI&amp;lt;15 was independently associated with the presence of silent strokes (OR 1.65, 95% CI: 1.05–2.57; p=0.028). SDNN&amp;lt;70ms and MHR&amp;lt;80 were not associated with silent strokes, neither in the SR group, nor in the AF group (Figure). Conclusions Reduced HRVI is independently associated with the presence of clinically silent strokes in an AF population, both when assessed during SR and during AF. Our data suggest that a short-term measurement of HRV in routine ECG recordings might contribute to identifying AF patients with clinically silent strokes. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swiss National Science Foundation