Beta-blocker Treatment Research Articles

Abstract 4136518: All-cause mortality for Patients with Preserved Ejection Fraction Heart Failure stratified by B-blocker Therapy and Presence of Permanent Pacemaker.

Background: Beta blockers (BB) and particularly high dose beta blockers might be beneficial for patients with heart failure with preserved ejection fraction (HFpEF), however their use is often limited by commonly coexisting sinus node dysfunction. It is unclear whether the presence of permanent pacemakers (PPM) allows for adequate therapy with BB which in turn confers a mortality benefit. Objective: We sought to evaluate differences in BB treatment between HFpEF patents with and without PPM and evaluate their effect on outpatient mortality. Methods: We identified patients admitted to 1 of 13 Northwell hospitals receiving intravenous diuretics in response to elevated BNP and included in our analysis only those with left ventricular ejection fraction >45%. Status on BB therapy and presence of PPM was assessed at discharge. The vital status of our cohort was identified for the length of the observation period. Results: Of 17,682 patients (42.8% female, 73.5 ± 15.7 years) admitted for HFpEF, 7,910 (44.7%) were discharged on BB, while PPM was present in 397 (2.3%). Treatment with BB was more common among patients with PPM (51.4% vs 48.6%, p=X). There were 1,316 deaths during a follow-up period of 2.4 ± 0.9 years post index admission. Mortality was highest among patients discharged on a BB without PPM and lowest among patients on both BB and PPM (log rank p=0.003) Conclusion: Additional studies are required to assess the complimentary role of pacing and BB therapy in patients with HFpEF.

Diagnostic Techniques for Infantile Subglottic Hemangiomas: A Scoping Review.

Infantile subglottic hemangioma (SGH) poses a risk of airway compromise if untreated. Traditionally, operative endoscopy (OH) diagnoses SGH, but since the discovery of beta-blockers' efficacy in treating infantile hemangiomas (IHs) in 2008, and advances in endoscopic technology, nonoperative methods have emerged. This review identifies endoscopic practices for diagnosing and monitoring infantile SGH during the oral beta-blocker treatment era. A comprehensive literature search in October 2022 and August 2023 covered PubMed, Embase, Cochrane Library, SCOPUS, and Web of Science. The search was limited to English-language studies published since 2008, considering this when propranolol was demonstrated as an effective treatment option for IH. The articles were screened for relevance based on predefined inclusion and exclusion criteria. After inclusion and exclusion criteria, sixty final studies were identified, describing 240 cases of infantile SGH. Most children were diagnosed using OE alone (73.3%; n = 176/240), 23.3% (n = 56/240) using office-based laryngoscopy procedures (OBPs) followed by OE, 3.3% using OBP alone (n = 8/240). There were no reported diagnostic endoscopy-related complications. Twenty-nine studies described using endoscopy plus diagnostic imaging to either confirm an SGH lesion, characterize the extent of disease spread, or rule out other causes of presenting symptoms. The proportion of infants diagnosed with OE alone decreased from 2008 to 2023. Operative endoscopy remains the SGH diagnostic standard, but OBP adoption is increasing. Further research is needed to determine the optimal SGH diagnosis and management approach. NA Laryngoscope, 2024.

The very long-term risk of stroke after acute coronary syndrome and geographic differences. The ABC-10* study on heart disease

Abstract Background Little is known about the very long-term risk of stroke among acute coronary syndrome (ACS) survivors. Methods In this prospective study, we enrolled 535 ACS patients admitted to hospitals in three Italian provinces, discharged alive and followed for 24 years or death. The patient's residency was classified into three urban and three nearby rural areas. Results All patients completed the follow-up (6142 Perso-years). 85 (16%) patients suffered an acute stroke. Patients median age was 67 years, 70% were male, and 318 patients were residing in rural areas. Patients who had a stroke and those who had not shared most of the demographic and clinical characteristics. The incidence rate of overall stroke was 14/1000 person-year. Cox analyses showed older age (HR 3.13;95%CI 2.31-4.26), male gender (HR 1.88;95%CI 1.20-2.95), baseline diabetes (HR 2.25 95%CI 1.37-3.69), heart failure (HR 2.69;95%CI 1.71-4.24), and higher albumin/creatinine ratio (HR 1.75;95%CI 1.33-2.30) were all associated with an increased risk of stroke. while higher baseline eGFR, reperfusion, statin and beta-blockers treatment during follow-up were associated with a decreased risk; HR (0.55 (95%CI 0.42-0.72), 0.45(95%CI 0.29-0.71), 0.21(95%CI 0.13-0.34), and 0.37(95%CI 0.23-0.57), respectively). In the multivariate analysis, only older age (HR1.55;95%CI 1.08-2.21; p=0.02) was an independent predictor of stroke while statin treatment was independently associated with a lower risk (HR 0.35;95% CI 0.21-0.58; p<0.0001). However, all these variables did not predict the risk of stroke in competing risk regression analysis where death was treated as the competing event. A sub-analysis of the 43 patients who had a fatal stroke (FS) revealed 7/1000 person-year FS IR. The Cox regression and competing risk analyses of predictors of FS showed similar results. Interestingly, we observed an association between geographic areas of residence and the long-term FS risk as the risk increased going from rural to urban (HR 2.08;95%CI 1.14-3.80; p=0.02) areas and from north to middle and south provinces (HR 1.47;95%CI 1.00-2.15; p=0.04) in the univariate Cox regression analysis. Results kept true using multivariate Cox and Competing risk regression models. Conclusion This analysis reveals the significant urban-rural difference in the very long–term risk of fatal stroke among unselected ACS patients which highlights the importance of implementing a preventive policy based on area-specific knowledge.

Clinical profile and prognosis of Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) in patients with previous Acute Coronary Syndrome (ACS)

Abstract Introduction Myocardial infarction with non-obstructed coronary arteries (MINOCA) may occur in patients with a personal history of ischaemic heart disease, making diagnosis even more difficult. In addition, the role of cardiovascular risk factors, which are well known in patients with acute myocardial infarction with obstructed arteries (MICAD), is less well defined in MINOCA. The aim of this study is to define the clinical characteristics, risk factors and long-term prognosis in patients with MINOCA and previous acute coronary syndrome (ACS). Methods A prospective, analytical, observational study was designed. Included all patients admitted to our centre with ACS between 2016 and 2023 in which a coronary angiography was performed. Patients were classified as MINOCA according to the definition of the 2020 European ACS guidelines. MINOCA patients with and without a history of previous ischaemic heart disease were compared. At follow-up, MACE was defined as all-cause death, hospitalisation, reinfarction and stroke. The median follow-up was 43 [IQR 20-71]. Results A total of 136 patients were included, of whom 17 had a history of ACS. The proportion of men was significantly higher in the group with previous ACS (82% vs 48%; p=0.008). Patients with a history of ACS had higher rates of smoking (71% vs 51%, p=0.139), more night work (80% vs 39%, p=0.017) and less stress (33% vs 61%, p=0.152). They also had more peripheral vascular disease (24% vs 3%, p=0.005), diabetes (41% vs 19%, p=0.042), dyslipidaemia (71% vs 43%, p=0.04) and a higher rate of atrial fibrillation (29% vs 9%, p=0.032). However, despite a higher rate of previous ventricular dysfunction (24% vs 3%, p=0.005), they had lower troponin levels on admission (62 [IQR 37-368] vs 152 [IQR 49-424]). We found no differences in the other comorbidities analysed (Table 1). On admission, patients with previous ACS had significantly more non-ST-segment elevation (29% vs 10%, P=0.05) and received more beta-blocker treatment (82% vs 57%, p=0.046). When analysing the mechanism of infarction, patients without previous ACS were more likely to have vasospasm and coronary embolism. However, there was a significantly higher rate of type II AMI (41% vs 18%, p=0.044) in the group with previous ACS. During follow-up, patients with a history of ACS are more likely to have a new infarction (7% vs 3%, p=0.3) or stroke (14% vs 6%, p=0.2). There was also a trend towards a higher incidence of MACE in patients with prior ACS, although this did not reach statistical significance (HR 2.379, 95% IC 0,883-6,405) (Table 2). Conclusion MINOCA patients with a history of ACS have distinct and worse epidemiological features in which classic cardiovascular risk factors play a significant role, with more ventricular dysfunction and atrial fibrillation. In addition, they appear to have a worse prognosis with increased cardiovascular complications. That might suggest a more MICAD-like profile.

Effects of beta blockers on outcome in patients with PAH with and without comorbid conditions: a Multicenter Prospective Cohort Study (BNP-PL)

Abstract Background The current guidelines do not recommend the use of beta-blockers (BB) in patients with pulmonary arterial hypertension (PAH) unless necessitated by comorbidities. However, the evidence regarding the role of BB in PAH is contradictory. This study investigates the effects of BB on clinical outcomes in patients newly diagnosed with PAH, stratified by the presence of cardiovascular comorbidities that justify their use. Methods We analyzed data from 806 patients newly diagnosed with PAH, who were prospectively enrolled from March 1, 2018, to August 31, 2023, in the multicentre registry, Database of Pulmonary Hypertension in the Polish population (BNP-PL). The primary endpoints were all-cause mortality and a composite of hospitalization due to right heart exacerbation, syncope, or death. The follow-up period for these patients extended until August 31, 2023. Comorbidities in the study group that indicated the need for BB therapy included hypertension, significant arrhythmia, and coronary artery disease. In the Cox regression analysis, the association between BB use and the predefined endpoints was adjusted for age, baseline European Society of Cardiology risk score, and upfront therapy. Results Among the 806 patients, BBs were administered to 469 (58.2%) at the time of PAH diagnosis. In the entire cohort, BB therapy was linked to increased all-cause mortality (29.6% vs 21.4%; p=0.005, Fig 1.A) and a higher incidence of the composite endpoint (34.1% vs 22.6%; p<0.0001, Fig 1.B). The Number Needed to Harm (NNH) for BB treatment, regarding mortality and the composite endpoint, were 12.1 and 8.7, respectively. In patients without comorbidities, BB use significantly raised the risk of both all-cause mortality (Hazard Ratio [HR] 1.81, 95% Confidence Interval [CI]: 1.01-3.15) and the composite endpoint (HR 1.85, 95% CI 1.09-3.14), after adjustments for age, baseline three-strata PAH mortality risk, and upfront therapy. However, in patients with at least one comorbidity, BB therapy showed a neutral effect on both outcomes. Across the whole group, the use of nonselective BB was associated with a higher risk of the composite endpoint (HR 1.78, 95% CI 1.13-2.82, p=0.01) compared to selective β1 agents, although this did not extend to all-cause mortality (HR 1.34, 95% CI 0.79-2.25, p=0.28). Conclusion BBs, particularly nonselective, pose significant risks in patients with PAH who lack comorbidities that justify their use.

Beta-Blocker Interruption or Continuation after Myocardial Infarction

BackgroundThe appropriate duration of treatment with beta-blocker drugs after a myocardial infarction is unknown. Data are needed on the safety and efficacy of the interruption of long-term beta-blocker treatment to reduce side effects and improve quality of life in patients with a history of uncomplicated myocardial infarction.MethodsIn a multicenter, open label, randomized, noninferiority trial conducted at 49 sites in France, we randomly assigned patients with a history of myocardial infarction, in a 1:1 ratio, to interruption or continuation of beta-blocker treatment. All the patients had a left ventricular ejection fraction of at least 40% while receiving long-term beta-blocker treatment and had no history of a cardiovascular event in the previous 6 months. The primary end point was a composite of death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for cardiovascular reasons at the longest follow-up (minimum, 1 year), according to an analysis of noninferiority (defined as a between-group difference of <3 percentage points for the upper boundary of the two-sided 95% confidence interval). The main secondary end point was the change in quality of life as measured by the European Quality of Life–5 Dimensions questionnaire.ResultsA total of 3698 patients underwent randomization: 1846 to the interruption group and 1852 to the continuation group. The median time between the last myocardial infarction and randomization was 2.9 years (interquartile range, 1.2 to 6.4), and the median follow-up was 3.0 years (interquartile range, 2.0 to 4.0). A primary-outcome event occurred in 432 of 1812 patients (23.8%) in the interruption group and in 384 of 1821 patients (21.1%) in the continuation group (risk difference, 2.8 percentage points; 95% confidence interval [CI], <0.1 to 5.5), for a hazard ratio of 1.16 (95% CI, 1.01 to 1.33; P=0.44 for noninferiority). Beta-blocker interruption did not seem to improve the patients’ quality of life.ConclusionsIn patients with a history of myocardial infarction, interruption of long-term beta-blocker treatment was not found to be noninferior to a strategy of beta-blocker continuation. (Funded by the French Ministry of Health and ACTION Study Group; ABYSS ClinicalTrials.gov number, NCT03498066; EudraCT number, 2017-003903-23.)

Short- and long-term effects of beta-blockers on symptoms of anxiety and depression in patients with myocardial infarction and preserved left ventricular function: a pre-specified quality of life sub-study from the REDUCE-AMI trial.

Among patients with myocardial infarction (MI) with preserved left ventricular ejection fraction (LVEF), the REDUCE-AMI trial did not demonstrate a benefit of beta-blocker vs. no beta-blocker treatment on all-cause mortality and recurrent myocardial infarction. The aim of this pre-specified sub-study was to investigate effects of beta-blockers on self-reported symptoms of anxiety and depression. In this parallel-group, open-label, registry-based randomized trial, assessments with the Hospital Anxiety and Depression Scale were obtained at hospitalization and two follow-up points (6-10 weeks and 12-14 months) after MI. Analyses were based on the intention-to-treat principle using linear mixed models, calculating both short- and long-term effects. From August 2018 through June 2022, 806 patients were enrolled. At baseline, 27% of patients were possible cases of anxiety (m, 5.6; SD, 3.9) and 14% were possible cases of depression (m, 3.9; SD, 3.2). Beta-blocker treatment had a negative effect on depressive symptoms at both follow-ups 1 (β = 0.48; 95% CI 09-0.86; P = 0.015) and 2 (β = 0.41; 95% CI = 0.01-0.81; P = 0.047), but no effect on anxiety. Beta-blocker treatment led to a modest increase in depressive symptoms among MI patients with preserved LVEF. This observed effect was most pronounced in individuals with prior beta-blocker treatment. In routine initiation and continuation of beta-blocker treatment, a risk of slightly increased depressive symptoms should be considered.

Betablockers and clinical outcome after surgical aortic valve replacement: a report from the SWEDEHEART registry.

Previous reports suggest that betablockers appear non-beneficial after surgical aortic valve replacement (SAVR). This study aims to clarify the associations between betablockers and long-term outcome after SAVR. All patients with isolated SAVR due to aortic stenosis in Sweden between 2006 and 2020, alive at 6 months after surgery, were included. Patients were identified in the SWEDEHEART registry, and records were merged with data from 3 other mandatory national registries. Association between dispensed betablockers and major adverse cardiovascular events (MACE) (all-cause mortality, myocardial infarction and stroke) was analyzed using Cox proportional hazards models, with time-updated data on medication and adjusted for age, sex and comorbidities at baseline. In total, 11849 patients were included [median follow-up 5.4 years (range 0-13.5)]. Betablockers were prescribed to 79.7% of patients at baseline, decreasing to 62.2% after 5 years. Continuing treatment was associated with higher risk of MACE [adjusted hazard ratio 1.14 (95% confidence interval, CI 1.05-1.23)]. The association was consistent over subgroups based on age, sex and comorbidities except atrial fibrillation [hazard ratio (HR) 1.05 (95% CI 0.93-1.19)]. A sensitivity analysis including time-updated data on comorbidites attenuated the difference between the groups [HR 1.04 (95% CI 0.95-1.14, P = 0.33)]. Treatment with betablockers did not appear to be associated with inferior long-term outcome after SAVR, when adjusting for new concomitant diseases. Thus, it is likely that it is the underlying cardiac diseases that are associated with MACE rather than betablocker treatment.

Beta-Blocker in Heart Rate Control and Cardio Protection: The Role of ADRB1 Variants and HCN4 Regulation – A Systematic Review

Elevated heart rate is linked to adverse cardiovascular outcomes. Sinoatrial (SA) nodes, hyperpolarization-activated cyclic nucleotide-gated-4 (HCN4) channels, and beta1-adrenergic receptor (ADRB1) are responsible for generating the heart rate. Beta-blockers have a cardioprotective effect on heart failure, including controlling heart rate. However, the responses to beta-blockers can vary among individuals. ADRB1 genetic variability may be contributed to the differential beta-blocker effect in heart failure. HCN4 also performs a crucial function in the pacemaker cells of the heart. Exploring the effect of beta-blockers in pacemaker cells is expanding the view of their role and their therapeutic response in heart failure. The objectives of this study were to identify ADRB1 genetic variants affecting heart rate response in heart failure subjects with beta-blocker treatment and to explore the effect of beta-blockers on HCN4 channels and SA nodes. A systematic review was performed using three databases. Eight of 668 manuscripts were selected. The systematic review found that ADRB1 genetic variants (A145G (Ser49Gly) and C1165G (Arg389Gly)) can affect heart rate response in beta-blocker-treated heart failure. The study also found that the percentage of patients with the Ser49Ser-Gly389X haplotype achieved a heart rate target was higher than other haplotypes. Individuals with the Arg389Arg genotype necessitated a markedly increased amount of beta-blocker dose to reach the identical heart rate target compared to those with the Gly389X gene variation. In addition, the review found that carvedilol, a beta-blocker derivative, demonstrated beneficial effects in inhibiting HCN-gated channels. Bisoprolol and carvedilol improved channel regulation in the SA Node by reversing the downregulation of HCN4 and sodium channels. In general, this systematic review provides important insights into beta-blockers in treating heart failure, specifically concerning the genetic variability of ADRB1 and the beta-blockers effect on the SA node and HCN4 channels.

Effects of beta-blockers on quality of life and well-being in patients with myocardial infarction and preserved left ventricular function-a prespecified substudy from REDUCE-AMI.

In the Randomized Evaluation of Decreased Usage of Beta-Blockers after Acute Myocardial Infarction (REDUCE-AMI) study, long-term beta-blocker use in patients after acute myocardial infarction (AMI) with preserved left ventricular ejection fraction demonstrated no effect on death or cardiovascular outcomes. The aim of this prespecified substudy was to investigate effects of beta-blockers on self-reported quality of life and well-being. From this parallel-group, open-label, registry-based randomized clinical trial, EQ-5D, and World Health Organization well-being index-5 (WHO-5) questionnaires were obtained at 6-10 weeks and 11-13 months after AMI in 4080 and 806 patients, respectively. We report results from intention-to-treat and on-treatment analyses for the overall population and relevant subgroups using Wilcoxon rank sum test and adjusted ordinal regression analyses. Of the 4080 individuals reporting EQ-5D (median age 64 years, 22% female), 2023 were randomized to beta-blockers. The main outcome, median EQ-5D index score, was 0.94 [interquartile range (IQR) 0.88, 0.97] in the beta-blocker group, and 0.94 (IQR 0.88, 0.97) in the no-beta-blocker group 6-10 weeks after AMI, OR 1.00 [95% CI 0.89-1.13; P>0.9]. After 11-13 months, results remained unchanged. Findings were robust in on-treatment analyses and across relevant subgroups. Secondary outcomes, EQ-VAS and WHO-5 index score, confirmed these results. Among patients after AMI with preserved left ventricular ejection fraction, self-reported quality of life and well-being was not significantly different in individuals randomized to routine long-term beta-blocker therapy as compared to individuals with no beta-blocker use. These results appear consistent regardless of adherence to randomized treatment and across subgroups which emphasizes the need for a careful individual risk-benefit evaluation prior to initiation of beta-blocker treatment.

Relevance of accurate QT correction in the assessment of long QT syndrome

BackgroundLong QT syndrome (LQTS) is a genetic cardiac disease, where the corrected QT (QTc) interval is prolonged. It can cause arrhythmias and lead to a sudden cardiac death. Duration of the QT interval depends on the heart rate and this dependency is treated with QT correction. However, the current QT correction methods have well known problems and limitations. ObjectiveWe study the relevance of QT correction method in evaluating the risk of LQTS. We evaluate the reliability of the present and recently developed QT correction methods to discriminate LQTS subjects from healthy controls. MethodsWe use the clinically prevalent QT correction methods, particularly Bazett and Fridericia, in comparison with the recently developed AccuQT method. The data of healthy controls and LQTS subjects is extracted from the Rochester THEW database. The analysis accounts for sex, major LQTS subtypes, and beta-blocker treatment. ResultsQT values corrected with AccuQT discriminate the healthy and LQTS samples with the best accuracy, leading to (TP, TN) = (0.87, 0.65) with the conventional 450 ms threshold for LQTS. Fridericia correction yields lower sensitivity (0.71), but comparable balanced accuracy, whereas Bazett shows significantly less accurate results due to overcorrection at lower heart rates. ConclusionThe selected QT correction method is important in the identification of LQTS. In particular, the use of Bazett correction should be questioned. Fridericia correction yields good results with respect to its simplicity. AccuQT has the best accuracy out of all the methods for LQTS discrimination. For practical applicability, however, AccuQT needs further validation in realistic clinical conditions.

Can the efficacy of a medical treatment be predicted based on the type of idiopathic premature ventricular contraction?

BackgroundPremature ventricular contractions (PVCs) are common arrhythmias with diverse clinical implications. This retrospective study aimed to evaluate the efficacy of medical treatments using various clinical, imaging, and electrocardiographic parameters in patients with idiopathic PVCs. MethodsA total of 1051 patients with idiopathic PVCs were retrospectively analyzed. Patients were categorized into three groups based on treatment response: beta-blocker (BB) responders (479 patients), calcium-channel blocker (CCB) responders (335 patients), and class 1c antiarrhythmic (AA) responders (237 patients). Clinical, imaging, and electrocardiographic data were collected and analyzed to assess the factors influencing treatment response. ResultsAge, left ventricular ejection fraction (LVEF), PVC QRS duration, CI variability, and multiple PVC morphologies were identified as significant factors affecting treatment response. Older age and lower LVEF were associated with better response to BB treatment, whereas CCB responders showed narrower QRS complexes. BB responders also exhibited higher CI variability, possibly linked to automaticity mechanisms. Moreover, the BB responder group had a higher frequency of multiple PVC morphologies. ConclusionThese findings emphasize the importance of tailored treatment approaches based on individual patient characteristics.

Echocardiographic assessment of left ventricular mechanics in individuals with mitral valve prolapse: a systematic review and meta-analysis.

During the last decade, a number of echocardiographic studies have employed speckle tracking echocardiography (STE) for assessing myocardial deformation properties in individuals with mitral valve prolapse (MVP), reporting not univocal results. Accordingly, we performed a systematic review and meta-analysis to summarize the main findings of these studies and to examine the overall influence of MVP on left ventricular (LV) global longitudinal strain (GLS). All echocardiographic studies assessing conventional echoDoppler parameters and myocardial strain indices in MVP individuals vs. controls without MVP, selected from PubMed and EMBASE databases, were included. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment of Case-Control Studies. Continuous data (LV-GLS) were pooled as a standardized mean difference (SMD) comparing MVP group with healthy controls. The overall SMD of LV-GLS was calculated using the random-effect model. The full-texts of 15 studies with 1088 individuals with MVP and 591 healthy controls were analyzed. Average LV-GLS magnitude was significantly, even though modestly, reduced in MVP individuals in comparison to controls (19.4 ± 3.4% vs. 21.1 ± 2.8%, P < 0.001). The overall effect of MVP on LV-GLS was small-to-medium (SMD - 0.54, 95%CI -0.76,-0.32, P < 0.001). Substantial heterogeneity was detected for the included studies, with an overall I2 statistic value of 75.9% (P < 0.001). Egger's test for a regression intercept gave a P-value of 0.58, indicating no publication bias. On meta-regression analysis, none of the moderators (the age, the percentage of females among MVP individuals, body mass index, heart rate and systolic blood pressure of MVP individuals, the degree of mitral regurgitation, the type of ultrasound machine employed for strain echocardiographic imaging and finally the beta blocker treatment) was significantly associated with effect modification (all P < 0.05). Regional strain analysis, performed by two-third of the studies, highlighted a more enhanced reduction in myocardial strain parameters at level of the LV basal infero-lateral segments in all directions (longitudinal, circumferential and radial), with apical sparing. The longitudinal strain impairment detected in MVP individuals is more regional than global, with peculiar involvement of the LV basal infero-lateral segments and relative apical sparing pattern.

The predictive risk factors associated with non-dipper profile in patients with type 2 diabetes and hypertension.

The non-dipper status represented by blood pressure reduction by less than 10 percent during sleep is present in about 50 percent of patients with type 2 diabetes (T2D) and hypertension, a pattern associated with more frequent cardiovascular complications and reserved prognosis. This study analyzed the predictive risk factors associated with the different dipper profiles, especially with the nocturnal pattern, following the mean arterial pressure (MAP), the mean heart rate (MHR), and the mean pulse pressure (MPP) in patients with T2D and hypertension, established by ambulatory blood pressure monitoring (ABPM). 166 consecutive patients with type 2 diabetes mellitus and hypertension were included in a cross-sectional study, and they underwent 24-hour ABPM. We excluded patients with secondary hypertension, acute coronary disease and heart failure, with oncologic or endocrine disease. The simple and multiple linear regression models were performed predicting 24-hour, day and night MAP, MHR, and MPP according to various predictors, using software R version 4.3.1. There were 80 non-dippers (48.20%), 57 dippers (34.34%), 22 reverse-dippers (13.25%) and seven extreme-dippers (4.21%). A statistically significant association was observed between MAP 24-hour and total cholesterol (TC) (higher TC values were associated with higher MAP /24 h values): adjusted coefficient B of the regression slope: 0.09, 95% confidence interval CI (0.04-0.15), p=0.003. In the multivariate analysis: adjusted B: 8.64, 95% CI (-14.67-2.61), p=0.006, beta-blockers reached the threshold of statistical significance in relation to MHR/24 h, their presence decreasing the heart rate. PP/24 hours was associated in the multivariate analysis with age: adjusted B: 0.45, 95% CI (0.05-0.85), p=0.28; abdominal circumference: 0.26, 95% CI (0.03-0.49), p=0.028, and total cholesterol: 0.1, 95% CI (0.02-0.17), p=0.013. Diabetic nephropathy was statistically significantly associated with PP/24 h: adjusted B: 10.19, 95% CI (1.24-19.14), p=0.027. High cholesterol was associated with higher values of MAP and PP. Beta-blocker treatment lowered non-dipper MHR. Age and AC were correlated with increased PP values. These are predictive risk factors associated with the status of non-dippers established by ABPM, and they represent a veritable link to the non-dipper pattern in patients with T2D and hypertension.

The heart rate response to the 6-min walk test in atrial fibrillation patients with or without beta-blockers: Referring to patients with sinus rhythm.

The aim was to evaluate the effect of beta-blockers (BB) on the response of heart rate (HR) to 6-min walk test (6MWT) in atrial fibrillation (AF) and whether the AF patients treated with BB have a similar HR response to 6MWT as the AF and sinus rhythm (SR) patients without BB treatment at the same resting HR level. The before-after study involving 74 AF patients was to evaluate the effect of BB treatment (pre-BB and with BB). The comparison study included 74 BB-treated AF patients (with BB), 74 matched AF patients without BB (no BB), and 74 SR patients. The percentage increase amplitude of HR (HR-PIA) in 6MWT was calculated: [(the exercise HR - the resting HR)/(the resting HR)] × 100%. The before-after study showed that BB treatment decreased the resting and mean exercise HR (98.6 ± 15.2 vs. 85.5 ± 11.2 bpm and 121.3 ± 17.3 vs. 109.0 ± 16.7 bpm) during 6MWT. The comparison study demonstrated that against the SR, the AF with BB and no BB groups have higher mean exercise HR-PIA (28.2 ± 17.1% and 22.0 ± 9.6%, vs. 6.9 ± 3.7%) when their resting HR is similar. Moreover, the mean exercise HR-PIA was also significantly higher in the with BB group than in the no BB group. In AF patients with relatively higher resting HR, BB treatment could decrease the resting and exercise HR during 6MWT. However, BB treatment could not effectively attenuate the exercise HR rise as compared with AF without BB treatment, even with similar resting HR levels.

Long-term Beta-Blocker Treatment after Acute Myocardial Infarction and with Preserved Left Ventricular Ejection Fraction

Long-term Beta-Blocker Treatment after Acute Myocardial Infarction and with Preserved Left Ventricular Ejection Fraction

Impact of early administration of beta-blocker and RAS inhibitor during VA-ECMO treatment for cardiogenic shock; the post-hoc study of the EARLY-UNLOAD trial

Abstract Funding Acknowledgements None. Background/introduction No data about timing and impact of beta-blocker (BB) or renin-angiotensin-aldosterone system inhibitor (RASi) administration for cardiogenic shock (CS) treated with venoatrial extracorporeal membrane oxygenation (VA-ECMO). Purpose To analyze an impact of early administration of BB or RASi during VA-ECMO treatment. Methods This study is a post-hoc analysis of the EARLY-UNLOAD trial (NCT04775472), the trial evaluated an impact of an early prophylactic unloading strategy using left atrial cannulation (LAC) performed within 12 hours from the initiation of VA-ECMO treatment for CS. Among total population (N=116), patients whose lactate was normalized during VA-ECMO and survived more than 2 days were included in this analysis (N=103). Patients were classified whether each medication (BB, RASi or one of BB or RASi) was administered during VA-ECMO or not. The primary endpoint was all-cause mortality. Survival analysis for a primary outcome and landmark analysis for all-cause mortality during different periods (&amp;lt;10 days, 10 to 30 days) were performed. Results BB, RASi, and BB or RASi were administered in 71.8%, 72.8%, and 83.5% of patients, respectively, during VA-ECMO treatment. In early treatment groups, Both BB and RASi were initiated on day 1 (as median). Duration of VA-ECMO treatment was longer in a group who treated with BB during VA-ECMO (8.5 days, vs 5.0 days as median, P = 0.003), and for RASi, it was comparable (8.0 days vs 7.0 days, P = 0.609). Incidence of 30-day all-cause mortality at were statistically comparable between groups (figure 1). The results of survival analysis are described in the figure 2. In Kaplan-Meier analysis, BB, RASi, and BB or RASi during VA-ECMO treatment was not associated with lower probability of 30-day all-cause mortality. Landmark analysis, however, showed lower probability of 10-day mortality in the group treated with BB (P by log-rank test = 0.045), RASi (P = 0.008) and BB or RASi (P=0.005) during VA-ECMO. Multivariate Cox proportional modellings also provided lower risk of 10-day all-cause mortality in groups with BB treatment (Hazard ratio [HR] = 0.26, 95% confidence interval [CI]=0.10-0.69, P = 0.007), RASi treatment (HR = 0.22, 95% CI = 0.08-0.56, P = 0.001) or BB or RASi (HR = 0.15, 95% CI = 0.05-0.41, P &amp;lt; 0.001) during VA-ECMO. RASi (HR = 0.47, 95% CI = 0.22-0.97, P = 0.041) or BB or RASi (HR = 0.37, 95% CI = 0.15-0.93, P = 0.038) treatment during VA-ECMO was also associated with lower risk of 30-day all-cause mortality. Conclusions In this post-hoc analysis of the EARLY-UNLOAD trial, administration of BB or RASi during VA-ECMO treatment for CS was associated with lower risk of short-term mortality.

Optimal Timing and Duration of Beta-Blocker Therapy for Preventing Postoperative Atrial Fibrillation: A Literature Review

This literature review explores the intricate landscape of postoperative atrial fibrillation (POAF), a common complication that arises following heart surgery. The analysis highlights the significant risks associated with POAF, including stroke, extended hospital stay, and increased healthcare costs. POAF, together with its transient character, indicates an augmented susceptibility to atrial fibrillation in the long run. Despite extensive research on preventive measures, such as beta-blocker medication, uncertainties remain regarding the optimal timing and duration of beta-blocker therapy for preventing POAF. The existing evidence suggests that starting beta-blocker treatment early, ideally within the first 24–48 hours after surgery, may be effective in reducing the occurrence of POAF. Nevertheless, there is a noticeable absence of agreement regarding the optimal length of this therapy. Conflicting viewpoints arise, with certain research calling for brief therapies, while others propose the possible benefits linked to extended treatment. This review highlights the urgent requirement for more research to precisely adjust guidelines, taking into account patient-specific factors and considering the consequences for long-term results. The call to action entails a request for the implementation of uniform definitions, the conduct of prospective randomized controlled trials, and the utilization of larger sample sizes in future investigations. These characteristics are considered critical in providing the medical community with strong evidence, which is crucial for making well-informed therapeutic decisions.

Target population for a selective cardiac myosin inhibitor in hypertrophic obstructive cardiomyopathy: Real-life estimation from the French register of hypertrophic cardiomyopathy (REMY)

BackgroundThe efficacy of current pharmacological therapies in hypertrophic cardiomyopathy is limited. A cardiac myosin inhibitor, mavacamten, has recently been approved as a first-in-class treatment for symptomatic hypertrophic obstructive cardiomyopathy. AimsTo assess the profile and burden of cardiac myosin inhibitor candidates in the hypertrophic cardiomyopathy prospective Register of hypertrophic cardiomyopathy (REMY) held by the French Society of Cardiology. MethodsData were collected at baseline and during follow-up from patients with hypertrophic cardiomyopathy enrolled in REMY by the three largest participating centres. ResultsAmong 1059 adults with hypertrophic cardiomyopathy, 461 (43.5%) had obstruction; 325 (30.7%) of these were also symptomatic, forming the “cardiac myosin inhibitor candidates” group. Baseline features of this group were: age 58±15years; male sex (n=196; 60.3%); diagnosis-to-inclusion delay 5 (1–12)years; maximum wall thickness 20±6mm; left ventricular ejection fraction 69±6%; family history of hypertrophic cardiomyopathy or sudden cardiac death (n=133; 40.9%); presence of a pathogenic sarcomere gene mutation (n=101; 31.1%); beta-blocker or verapamil treatment (n=304; 93.8%), combined with disopyramide (n=28; 8.7%); and eligibility for septal reduction therapy (n=96; 29%). At the end of a median follow-up of 66 (34–106) months, 319 (98.2%) were treated for obstruction (n=43 [13.2%] received disopyramide), 46 (14.2%) underwent septal reduction therapy and the all-cause mortality rate was 1.9/100 person-years (95% confidence interval 1.4–2.6) (46 deaths). Moreover, 41 (8.9%) patients from the initial hypertrophic obstructive cardiomyopathy group became eligible for a cardiac myosin inhibitor. ConclusionsIn this cohort of patients with hypertrophic cardiomyopathy selected from the REMY registry, one third were eligible for a cardiac myosin inhibitor.

Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction

BackgroundMost trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin–angiotensin–aldosterone system antagonists.MethodsIn a parallel-group, open-label trial performed at 45 centers in Sweden, Estonia, and New Zealand, we randomly assigned patients with an acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary end point was a composite of death from any cause or new myocardial infarction.ResultsFrom September 2017 through May 2023, a total of 5020 patients were enrolled (95.4% of whom were from Sweden). The median follow-up was 3.5 years (interquartile range, 2.2 to 4.7). A primary end-point event occurred in 199 of 2508 patients (7.9%) in the beta-blocker group and in 208 of 2512 patients (8.3%) in the no–beta-blocker group (hazard ratio, 0.96; 95% confidence interval, 0.79 to 1.16; P=0.64). Beta-blocker treatment did not appear to lead to a lower cumulative incidence of the secondary end points (death from any cause, 3.9% in the beta-blocker group and 4.1% in the no–beta-blocker group; death from cardiovascular causes, 1.5% and 1.3%, respectively; myocardial infarction, 4.5% and 4.7%; hospitalization for atrial fibrillation, 1.1% and 1.4%; and hospitalization for heart failure, 0.8% and 0.9%). With regard to safety end points, hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker occurred in 3.4% of the patients in the beta-blocker group and in 3.2% of those in the no–beta-blocker group; hospitalization for asthma or chronic obstructive pulmonary disease in 0.6% and 0.6%, respectively; and hospitalization for stroke in 1.4% and 1.8%.ConclusionsAmong patients with acute myocardial infarction who underwent early coronary angiography and had a preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use. (Funded by the Swedish Research Council and others; REDUCE-AMI ClinicalTrials.gov number, NCT03278509.)