Beta-blockers Research Articles

WEARABLE CARDIOVERTER–DEFIBRILLATORS IN CLINICAL PRACTICE IMPLEMENTATION OF THE ANMCO POSITION PAPER FOR APPROPRIATE USE OF THE WEARABLE CARDIOVERTER DEFIBRILLATOR

Abstract Introduction Wearable cardioverter–defibrillators (WCD) have emerged as a valuable tool in the management of patients at risk for life–threatening arrhythmias. These devices offer a non–invasive and temporary solution, providing continuous monitoring and the potential for prompt defibrillation when needed. In this study, we explore the indications for WCD and evaluate arrhythmic events through comprehensive monitoring. Methods From November 2022 to December 2023, we conducted an outpatient follow–up of 18 patients receiving WCD. Regular check–ups and comprehensive echocardiography were performed to optimize therapy based on specific indications for each patient. Results The average age of the patients was 59.3±17.4 years, with 79% being male. Among the cohort, 58% had hypertension, and a similar percentage comprised smokers and individuals with dyslipidemia, while 32% were diabetic. The indications for receiving WCD were: de novo diagnosis of dilated cardiomyopathy with reduced ejection fraction in 9 (50%) patients, recent acute coronary syndrome and ejection fraction < 35% in 5 (28%), cardiac electronic device infections in 3 (17%) patients and myocarditis with electrical instability in 1 (5%) patient. Patients were in optimal medical therapy (OMT) tailored to their specific comorbidities, with 84% on renin–angiotensin–aldosterone system inhibitors, 95% on beta–blockers, 53% on mineralocorticoid receptor antagonists, 53% on sodium–glucose cotransporter–2 inhibitors, and 37% on antiarrhythmics. The average follow–up was 64±45 days according to specific etiology, with a daily wearing time of 22.9±1.1 hours. No device interventions were recorded. At the end of the follow–up period, 6 (33%) patients still required implantable cardioverter–defibrillator (ICD). Among these, 4 patients (22%) underwent to ICD implantation, 3 for secondary prevention, and 1 for primary prevention, while notably, 2 (11%) patients, declined the procedure. Conclusions The use of wearable cardioverter–defibrillators in the outpatient setting for patients at risk of life–threatening arrhythmias allowed to optimize therapy and restrict the indications for ICD, in our cohort up to 67%, with a good safety profile due to the low incidence of device interventions.

IMPROVING THE KNOWLEDGE, RISK STRATIFICATION AND OUTCOMES IN ADVANCED HEART FAILURE. THE ISMETT HEART FAILURE REGISTRY

Abstract Background Advanced heart failure (AdHF) accounts for approximately 10% of patients in HF clinics worldwide. Clinical management of patients with AdHF remains challenging and most of the available studies focus on chronic but not advanced HF. Registry studies may provide important insights into this specific population. Methods All consecutive patients referred to our centre for AdHF therapies candidacy (left ventricular assist device (LVAD), heart transplant (HTx)) are prospectively studied and enrolled in the registry. On the same day, all patients undergo a comprehensive clinical and instrumental examination, including electrocardiogram, echocardiography, extended laboratory tests and right heart catheterisation. Most patients also undergo a cardiopulmonary exercise test and, in the case of a non–ischaemic aetiology, cardiac magnetic resonance imaging and genetic testing, if not already performed. Echocardiography is also performed to assess advanced echocardiographic measures (biventricular and atrial strain, myocardial work, 3–D chambers assessment). Results Forty–five patients were enrolled from March 1, 2023 to December 22, 2023 (enrolment rate 4.5 patients/month). Mean age was 54 years and 2/3 were male. Median disease duration was 69 (28–165) months. Non–ischemic HF was the most common aetiology with a NYHA IV prevalence of 4% (all others were in NYHA III). 31% of patients had chronic kidney disease and overall liver function was preserved. 67% of patients were treated with sacubitril/valsartan, > 90% were taking beta–blockers (median dose 4.8 mg bisoprolol–equivalent dose) and 84% SGLT2 inhibitors. Both standard and advanced echocardiography showed features of advanced disease. Over a median follow–up of 4 (2 – 6) months 2 (4%) patients died, 5 (11%) underwent urgent HTx and 8 (18%) underwent LVAD implantation. For most variables, there was a trend showing that patients with events were sicker but, currently, the sample size limited the statistical power. Conclusions A systematic comprehensive evaluation of patients with AdHF evaluated for advanced HF therapies could help to reduce the knowledge gap for this high–risk HF population.

MULTIDISCIPLINARY APPROACH TO A DIFFICULT CASE OF ACUTE HEART FAILURE DUE TO POSSIBILE ISOLATED CARDIAC SARCOIDOSIS

Abstract Background Cardiac sarcoidosis (CS) is a rare, infiltrative cardiomyopathy that results from granulomatous inflammation affecting the heart with high morbidity and mortality. It is usually associated with a systemic (i.e. pulmonary) involvement, but lone heart involvement has been described. Even with extensive multidisciplinary evaluation making a firm diagnosis is difficult, especially in case of isolated CS where the endomyocardial biopsy (EBM) diagnostic yield is low (20–30%). Case Description A 71–year–old patient, heavy smoker with no previously known diseases, was admitted with a 3–month history of dyspnea. On admission he showed typical features of heart failure with reduced ejection fraction (HFrEF). A coronary angiography excluded coronary artery disease, while echocardiography (TTE), cardiac magnetic resonance (CMR), and positron emission tomography (FDG–PET) showed a pattern consistent with a non–ischemic dilated cardiomyopathy with reduction in systolic function, and signs of active inflammation (highly suspected CS). Two electroanatomic mapping driven EBM were made but no clear histological signs of CS (i.e., granulomatous inflammation) were detected. The patient was treated with corticosteroids and HFrEF optimal medical therapy (sacubitril/valsartan, mineralocorticoid receptor antagonists, beta–blockers, dapagliflozin) and a temporary wearable defibrillator (LifeVest) was applied. At 2–month follow–up, despite a moderate improvement in the systolic function and HF symptoms, after a multidisciplinary discussion, considering the extensive left ventricle scar, inflammatory involvement, and the presence of multiple non–sustained ventricular tachycardia, a permanent cardioverter–defibrillator (ICD) was implanted. Conclusion This case highlights how, even with (repeated) extensive multidisciplinary evaluation (TTE, CRM, FGD–PET, EBM), a definitive diagnosis of isolated CS often remains presumptive. The presence of an experienced cardiomyopathy team (HF specialists, cardiac imager, electrophysiologists, internal medicine doctor) can help in the diagnostic–therapeutic management of these patients with inflammatory heart disease.

MYOCARDITIS, CORONARY ARTERY DISSECTION OR BOTH: A JUVENILE ENIGMA

Abstract A 26–year–old man was admitted to the Coronary Care Unit for severe, non–irradiated, oppressive anterothoracic pain. He had no relevant pathological history, but reported an episode of gastroenteritis the week before. EKG showed sinus rhythm and accelerated idioventricular rhythm phases. Blood pressure and 2D echo were normal. Inflammation indeces were negative, hsTnT reached a peak of 2026 ng/L. Despite the absence of inflammation signs, our first guess was myocarditis. Cardiac magnetic resonance (CMR) was performed: T2w–STIR images showed edema of the middle inferior wall and of the mid–basal anterior and anterolateral wall, while T1–weighted post gadolinium images showed transmural enhancement of the mid–basal anterior, antero lateral and inferior walls with a dubious origin from the sub endocardium in the anterior and anterolateral segments; LVEF was 55%. Invasive coronary angiography (ICA) was performed to rule out ischemic etiology: LAD showed a very thin lumen in its periphery and two obtuse marginal branches had an amputated appearance: it made us think of healing dissections. Then it turned out that the patient have been working out with heavy weights the day before: we therefore considered spontaneous coronary artery dissection. Such hypothesis was consistent with the absence of inflammations indices, but didn’t explain the basal and middle inferior involvement that CMR had shown. On the other hand, the angiographic finding may be consistent with peripheral vascular suffering linked to myocarditis induced inflammation. To date, we haven’t found univocal interpretation. Anti–remodeling therapy with IACE and beta blockers was administered, in addition to acetylsalicylic acid. CMR will be performed in two months and may provide further results once the edema will be reabsorbed. ICA will be repeated to make sure that distal coronary blood flow is improved. Take Home Messages Myocarditis can also occur with no signs of inflammation. In myocarditis it has been demonstrated that slower distal coronary blood flow may occur, due to the increase in peripheral vascular resistance linked to the presence of edema. In the acute phase, especially if CMR is performed very early, the large amount of edema can make the enhancement transmural, masking the site of origin of the damage.

THE HF–ABCDE+FG APPROACH IN HEART FAILURE: A SIMPLIFIED DECISION– MAKING ALGORITHM FOR MANAGEMENT IN EMERGENCY DEPARTMENT

Abstract The–HF– ABCDE+FG protocol is an easy to memorize algorithm for diagnosis and treatment of Heart failure (HF) in the setting of Emergency Department (ED). The acronym “ABCDE” recalls the more famous ABCDE sequence proposed in Advanced Life Support (ALS), the most widely used and standardized approach to critical patients in the ED. Using a similar approach, the algorithm here proposed can help to recall the main elements of the patient’s assessment presenting acute heart failure (AHF) concerning diagnosis and early therapy. It should be interpreted as a continuum since each step is partially overlapped and mnemonically linked to the previous and to the next one. As Acute heart failure can present with a variable pattern of signs and symptoms, diagnosis in the Emergency Department can be supported by a rapid and easy to memorize pathway made up of 5 steps: A (history assessment), B (blood exams/ blood gas analysis), C (Chest X–Ray), D (Dysfunction– lung anch heart ultrasound), E (Electricity– verify ICD or PM when implanted). On the other hand, with reference to the therapeutic algorithm, we suggest an extended protocol ABCDE+FG: each word of the acronym stands for a Class I recommendation coming from 2021 ESC Guidelines: A (ACE–i/ ARBs/ARNI), B (standing for Beta–Blockers), C (anti–choagulation) and D (Diuretics) which represent the standard desease–controlling therapy. In addiction, attention must be paid to associated conditions, like underlying electrical instability requiring PM or ICD (E standing for Electrical Therapy), iron deficiency (F standing for Ferric Carboxymaltose) and poor glycemic control (G standing for Glyfozines). In fact, it has been demonstrated that an optimyzed therapy from a very early stage can deeply impact on the evolution of desease and remarkably reduce further accesses for AHF. Thus, once the patient has been stabilyzed in the ED, we suggest to initiate the most appropriate therapy as soon as possible and eventually send the patient to the best setting of care (discharge, short observation, non intensive/intensive care).

REAL WORLD USAGE OF RANOLAZINE FOR ANTIARRHYTHMIC PURPOSES: SINGLE CENTER EXPERIENCE

Abstract Introduction Ranolazine is a late sodium current blocking drug developed as an antianginal agent, with good preliminary efficacy data even for antiarrhythmic purposes (both at atrial and at ventricular level). Objectives To evaluate patients’ clinical characteristics and antiarrhythmic efficacy of ranolazine in subjects with a history of atrial and/or ventricular arrhythmias, isolated or repetitive. Patients and methods we included patients who received a first prescription of ranolazine for antiarrhythmic purposes in our center from 1/2022 to 11/2023 and evaluated the survival free from major arrhythmic relapses/ablation. Results 93 patients were enrolled (66±13 years, 15% women): 59% with arterial hypertension, 26% diabetics, 46% with post–ischemic dilated heart disease, 32% with primary cardiomyopathy (including 11% with hypertrophic cardiomyopathy, 10% with LMNA, 14% with TTN), 46% with implantable cardioverter defibrillator, 9% with pacemaker. The mean LV ejection fraction was 42 ± 15%, the mean serum creatinine 1 ± 0.3 mg/dL. Half (50%) had a history of atrial arrhythmias in the 6 months before starting the drug, mainly paroxysmal atrial fibrillation (AF), 67% of ventricular arrhythmias (VAs), mainly isolated and repetitive premature ventricular beats (PVB, 47% of the total), but also sustained or treated VAs (n=18, 19%). Overall, 18% of patients had already undergone AF ablation, 13% ventricular tachycardia ablation, 3% cardiac sympathetic denervation. Finally, 95% of patients were on beta–blocker therapy and 28% were on amiodarone. Ranolazine was prescribed at an average initial dose of 535± 150 mg. The majority (54%) of patients (n=50) had a follow–up longer than 3 months (median 9 months, IQR 6–14); in 6% the drug was stopped due to intolerance and the average dose at the last FU was 641 ± 150 mg. Twenty–eight percent of patients with paroxysmal/persistent atrial arrhythmias had relapses, requiring ablation in 6%. Among patients with major VAs, 57% suffered recurrences, but only 19% required ablation (invasive in 2 cases, non–invasive in 1 case). Finally, among the patients with PVBs, none suffered major VAs or required PVB/VA ablation. Conclusions This is the largest available case–series reporting about the real–world usage of ranolazine for antiarrhythmic purposes. Our single center experience supports ranolazine’s good safety and tolerability and shows encouraging efficacy results in terms of clinical stabilization of complex patients.

THE COMPLEX WORLD OF NON CRITICAL CORONARY ARTERIES DISEASE

Abstract Background and Aim Acute coronary syndrome (ACS) with non–critical coronary arteries represents a major diagnostic, therapeutic and prognostic challenge for clinicians. The aim was to compare clinical–anamnestic characteristics and assess the prognosis of three cohorts with ACS with non–critical coronary arteries i.e. Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA), type 2 myocardial infarction (MI) and Takotsubo syndrome (TTS). Methods In this single center observational study, 18223 patients who underwent coronary angiography between 2005 and 2022 were retrospectively analyzed. The final cohort included 676 patients with initial presentation as NSTEMI (301 MINOCA, 237 type 2 MI and 138 TTS). Results The median age was 68±11, with the TTS population being the oldest (72±10, p<0.01), presenting greater hypotension (p<0.01), tachycardia (p<0.01), and fewer cardiovascular risk factors, such as diabetes (p<0.01) and hypertension (p<0.01). The TTS cohort had worse LVEF on admission (p<0.01) and on discharge (p<0.01) (Fig. 1). At Kaplan–Meier analysis, patients with type 2 MI were more prone to the composite endpoint, while the TTS group was less likely (p<0.01) (Fig. 2). In the overall cohort, ACEi/ARB therapy on admission was an independent predictor of the composite endpoint (HR: 1.58;p=0.01), while dual antiplatelet therapy (DAPT) (HR: 0.59;p=0.01) and statin (HR: 0.71;p=0.03) at discharge were protective. After stratification according to diagnosis, ACEi/ARB therapy remained a negative predictor only in the type 2 MI cohort (HR: 2.03;p=0.01) as well as beta–blocker therapy at admission in TTS (HR: 2.97;p=0.03), while statin therapy remained protective in the MINOCA (HR: 0.51;p=0.01) and DAPT therapy in the TTS group (HR: 0.21;p=0.04) at discharge. Although a substantial number of patients with all three diagnoses achieved the endpoint, the multivariable Cox regression analysis indicated that type 2 MI, in addition to older age, male gender, worse LVEF, and anemia, is an independent factor for worse outcomes (Fig. 3). Conclusions Among all cohorts, T2 MI were associated with worse outcome. The use of DAPT in TTS and Statins in the MINOCA group showed a protective role. Since the TTS population was more compromised, BB use in the ADHF phase of TTS could predict a poorer outcome as much as ACEI/ARB use at admission could be a marker of greater early LV impairment of the T2 MI cohort, which was an independent predictor for worst outcome.

A LONG QT SYNDROME WITHOUT MANIFESTATION

Abstract A 66–year–old Caucasian woman presented for outpatient evaluation due to elevated blood pressure levels at home (approximately 220/120 mmHg) and a significant family history of long QT syndrome. The index case in the family appeared to be her sister, investigated following an ECG showing markedly prolonged QT interval and a family history of sudden cardiac death. The patient underwent genetic analysis, revealing a positive mutation in KCNQ1. She was currently on treatment with Levotiroxina for recently discovered hypothyroidism.The ECG showed sinus rhythm with a heart rate of 85 bpm, signs of left ventricular hypertrophy, particularly Sokolow (SV1 + RV6 70 mm) and Peguero Lo Presti (SD + SV4 50 mm). The QTc interval was 515 ms (Bazett). Echocardiography revealed severe left ventricular hypertrophy (SIVd 14 mm; PWd 12 mm; LVMi 128 g/m2; RWT 0.5) with normal overall systolic function (EF 60%). No significant valvular pathologies were observed, and the right ventricle appeared normal in size and function.The hypertrophy was attributed to uncontrolled severe arterial hypertension. However, the identification of a prolonged QT interval in a patient with a strong family component (Schwartz score 4, high probability) led to genetic testing, confirming a mutation in KCNQ1. As the patient was asymptomatic with a low risk of major arrhythmias over the next 5 years (1–2–3–LQTS–risk score 2.77%), she entered follow–up and received beta–blocker therapy, specifically nadolol, combined with other antihypertensive medications.This clinical case describes an entire family with LQTS1 (type 1) positive for KCNQ1 mutation, exhibiting phenotypic manifestations distinct from those reported in the literature. Notably, there was a prevalence in females, and the condition was incidentally discovered during a routine checkup conducted for unrelated reasons, without any history of major arrhythmias.Long QT syndrome (LQTS) is characterized by a prolonged QT interval, predisposing individuals to life–threatening arrhythmias leading to syncope and sudden death. Mutations in genes encoding ion channels account for 75% of LQTS cases. LQTS1, associated with a "loss–of–function" mutation in the KCNQ1 gene, represents one of the three genetic subtypes. LQTS1 typically manifests with arrhythmias in childhood, with a male predominance. Adrenergic triggers are crucial precipitants for arrhythmic events

Identifying a Case of an Atenolol-induced Papulosquamous Eruption

While beta-adrenergic blocking agents (beta blockers) are generally safe, their incidence of medication-induced cutaneous eruptions remain under-recognized in the primary care setting. The adverse dermatologic effects of these medications may arise in the days to years following drug initiation, contributing to its delayed diagnosis and management. Here we report a case of a papulosquamous drug eruption in an older adult due to atenolol. We also discuss pertinent morphologic findings, diagnostic methods, management, and how to distinguish this type of eruption from other papulosquamous disorders.

ASSOCIATION OF BETA BLOCKER USE AND COPD MORTALITY: A SYSTEMATIC REVIEW

Background: Chronic obstructive pulmonary disease (COPD) it is currently the third greatest cause of mortality worldwide and one of the main causes of morbidity Aims: This systematic review is to review the association of beta blocker use and COPD mortality. Methods: This study demonstrated compliance with all requirements by means of a comparison with the standards established by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020. Thus, the specialists were able to guarantee that the research was as current as feasible. Publications released between 2014 and 2024 were considered for this search strategy. This was accomplished by utilizing a number of distinct online reference sites, including Pubmed, ScienceDirect, and SagePub. It was determined that reviews, previously published works, and partially completed works would not be included. Result: In the PubMed database, the results of our search brought up 249 articles, whereas the results of our search on SCIENCE DIRECT brought up 18.876 articles, our search on SAGEPUB brought up 4.844 articles. The results of the search conducted for the last year of 2014 yielded a total 131 articles for PubMed, 6.875 articles for SCIENCE DIRECT and 1.840 articles for SAGEPUB. In the end, we compiled a total of 8 papers, 5 of which came from PubMed, 2 of which came from SCIENCE DIRECT and 1 of which came from SAGEPUB. We included eight research that met the criteria. Conclusion: In summary, beta blockers showed the effect to reduce the exacerbation or exacerbation related mortality of COPD in some cases. More studies needed in the future for more evidence of the use of beta blockers as the treatments in patients with COPD.

Validation of Baveno VII criteria for clinically significant portal hypertension by two-dimensional shear wave elastography.

The Baveno VII consensus proposed criteria for the non-invasively diagnosis of clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease (cACLD). The performance of Baveno VII criteria for assessing CSPH by two-dimensional shear wave elastography (2D-SWE) had not been well validated. We aimed to validate the performance of Baveno VII criteria for rule-in and rule-out CSPH by 2D-SWE. This is an international multicenter study including cACLD patients from China and Croatia with paired liver stiffness measurement (LSM), spleen stiffness measurement (SSM) by 2D-SWE, and hepatic venous pressure gradient (HVPG) were included. CSPH was defined as HVPG ≥ 10mmHg. A total of 146 patients with cACLD were enrolled, and finally 118 patients were included in the analysis. Among them, CSPH was documented in 79 (66.9%) patients. Applying the Baveno VII criteria for rule-out CSPH by 2D-SWE, [LSM ≤ 15kPa and platelet count ≥ 150 × 109/L] OR SSM < 21kPa, could exclude CSPH with sensitivity > 90% (93.5 or 98.7%) but negative predictive value < 90% (74.1 or 85.7%). Using the Baveno VII criteria for rule-in CSPH by 2D-SWE, LSM ≥ 25kPa OR SSM ≥ 50kPa, could diagnose CSPH with 100% specificity and 100% positive predictive values. Baveno VII criteria by 2D-SWE showed a good diagnostic performance for ruling in but not for ruling out CSPH, which might become an emerging non-invasive elastography tool to select the patients who needed non-selective beta blocker therapy.

Midodrine plus propranolol versus propranolol alone in preventing first bleed in patients with cirrhosis and severe ascites: a randomized controlled trial.

Propranolol, a non-selective beta-blocker, commonly used to prevent variceal bleed, but might precipitate circulatory dysfunction in severe ascites. Midodrine, an alpha-1 adrenergic agonist improves renal perfusion and systemic hemodynamics. Addition of midodrine might facilitate higher maximum tolerated dose (MTD) of propranolol, thereby less risk of variceal bleed in cirrhosis patients with severe ascites. 140 patients with cirrhosis and severe/refractory ascites were randomized- propranolol and midodrine (Gr.A,n = 70) or propranolol alone (Gr.B,n = 70). Primary outcome was incidence of bleed at 1year. Secondary outcomes included ascites control, achievement of target heart rate (THR), HVPG response and adverse effects. Baseline characteristics were comparable between two groups. Cumulative incidence of bleed at 1year was lower in Gr.A than B (8.5%vs.27.1%,p-0.043). The MTD of propranolol was higher in Gr.A (96.67 ± 36.6mg vs. 76.52 ± 24.4mg; p-0.01) and more patients achieved THR (84.2%vs.55.7%,p-0.034). Significantly higher proportion of patients in Gr.A had complete resolution of ascites [17.1%vs.11.4%,p-0.014), diuretic tolerance (80%vs.60%,p-0.047) at higher doses(p-0.02) and lesser need for paracentesis. Patients in Gr.A also had greater reduction in variceal grade (75.7%vs.55.7%;p-0.01), plasma renin activity (54.4% from baseline) (p = 0.02). Mean HVPG reduction was greater in Gr.A than B [4.38 ± 2.81mmHg(23.5%) vs. 2.61 ± 2.87mmHg(14.5%),p-0.045]. Complications like post-paracentesis circulatory dysfunction and spontaneous bacterial peritonitis on follow-up were higher in Gr.B than A (22.8%vs.51.4%,p = 0.013 and 10%vs.15.7%, p = 0.03, respectively). Addition of midodrine facilitates effective use of propranolol in higher doses and greater HVPG reduction, thereby preventing first variceal bleed, reduced paracentesis requirements with fewer ascites- related complications in patients with cirrhosis with severe/refractory ascites.

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.

Trends of Antihypertensive Prescription Among US Adults From 2010 to 2019 and Changes Following Treatment Guidelines: Analysis of Multicenter Electronic Health Records.

Guidelines for the use of antihypertensives changed in 2014 and 2017. To understand the effect of these guidelines, we examined trends in antihypertensive prescriptions in the United States from 2010 to 2019 using a repeated cross-sectional design. Using electronic health records from 15 health care institutions for adults (20-85 years old) who had ≥1 antihypertensive prescription, we assessed whether (1) prescriptions of beta blockers decreased after the 2014 Eighth Joint National Committee (JNC 8) report discouraged use for first-line treatment, (2) prescriptions for calcium channel blockers and thiazide diuretics increased among Black patients after the JNC 8 report encouraged use as first-line therapy, and (3) prescriptions for dual therapy and fixed-dose combination among patients with blood pressure ≥140/90 mm Hg increased after recommendations in the 2017Hypertension Clinical Practice Guidelines. The study included 1 074 314 patients with 2 133 158 prescription episodes. After publication of the JNC 8 report, prescriptions for beta blockers decreased (3% lower in 2018-2019 compared to 2010-2014), and calcium channel blockers increased among Black patients (20% higher in 2015-2017 and 41% higher in 2018-2019, compared to 2010-2014), in accordance with guideline recommendations. However, contrary to guidelines, dual therapy and fixed-dose combination decreased after publication of the 2017 Hypertension Clinical Practice Guidelines(9% and 11% decrease in 2018-2019 for dual therapy and fixed-dose combination, respectively, compared to 2015-2017), and thiazide diuretics decreased among Black patients after the JNC8 report (6% lower in 2018-2019 compared to 2010-2014). Adherence to guidelines on prescribing antihypertensive medication was inconsistent, presenting an opportunity for interventions to achieve better blood pressure control in the US population.

Temporal trend of first-line drug choice and treatment continuity for hypertension among citizens 75 years or over - a register-based, cohort study

BackgroundLimited knowledge of antihypertensive treatment of the elderly potentially impedes effective strategies for hypertension management in this growing patient group. We aimed to investigate temporal trends for first-line drug choice for antihypertensive treatment and treatment continuity among patients ≥75 years from 2000 to 2021. MethodsUsing nationwide Danish registers, patients ≥75 years initiated for the first time on antihypertensive drugs: Angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), beta blockers (BB), calcium channel blockers (CCB), thiazides, or combinations, were identified. Patients with other indications than hypertension were excluded. Treatment continuity was described using claimed prescriptions the first 180 days following study entry. ResultsFrom 2000 to 2021, 170,769 patients (median age 80 years [interquartile range:77–84], 60.3% female) were included. From 2000 to 2003 to 2015–2021 the proportion of first-line drug choice increased for ACEi (8.7% to 14.9%), ARB (4.1% to 23.9%), and CCB (10.7% to 27.6%), decreased for thiazides (60.6% to 15.9%) and remained stable for BB (12.9% to 14.1%) and combinations (2.9% to 3.6%). For 157,457 patients alive after 180 days, discontinuation was highest among patients initiated on thiazides (28.3%) whereas most patients continued the same single drug regimen if they started on ACEi (55.2%), ARB (65.0%), BB (57.2%) or CCB (59.3%). ConclusionsFrom 2000 to 2021 thiazides have been replaced by ACEi, ARB and CCB. Thiazides had the lowest treatment continuity while ARB appeared preferred slightly over ACEi. Differences in adherence in relation to first-line drug choice may warrant scrutiny regarding recommendations for the elderly.

Comparison of safety and efficacy between Nirmatrelvir-ritonavir and molnupiravir in the treatment of COVID-19 infection in patients with advanced kidney disease: a retrospective observational study

Nirmatrelvir-ritonavir is used in patients with coronavirus disease 2019 (COVID-19) with normal or mild renal impairment (eGFR ≥30ml/min per 1.73m2). There is limited data regarding its use in advanced kidney disease (eGFR <30ml/min per 1.73m2). We performed a retrospective territory-wide observational study evaluating the safety and efficacy of nirmatrelvir-ritonavir when compared with molnupiravir in the treatment of patients with COVID-19 with advanced kidney disease. We adopted target trial emulation using data from a territory-wide electronic health record database on eligible patients aged ≥18 years with advanced kidney disease (history of eGFR <30ml/min per 1.73m2) who were infected with COVID-19 and were prescribed with either molnupiravir or nirmatrelvir-ritonavir within five days of infection during the period from 16 March 2022 to 31 December 2022. A sequence trial approach and 1:4 propensity score matching was applied based on the baseline covariates including age, sex, number of COVID-19 vaccine doses received, Charlson comorbidity index (CCI), hospitalisation, eGFR, renal replacement therapy, comorbidities (cancer, respiratory disease, myocardial infarction, ischaemic stroke, diabetes, hypertension), and drug use (renin-angiotensin-system agents, beta blockers, calcium channel blockers, diuretics, nitrates, lipid lowering agents, insulins, oral antidiabetic drugs, antiplatelets, immuno-suppressants, corticosteroids, proton pump inhibitors, histamine H2 receptor antagonists, monoclonal antibody infusion) within past 90 days. Individuals were followed up from the index date until the earliest outcome occurrence, death, 90 days from index date or the end of data availability. Stratified Cox proportional hazards regression adjusted with baseline covariates was used to compare the risk of outcomes between nirmatrelvir-ritonavir recipients and molnupiravir recipients which include (i) all-cause mortality, (ii) intensive care unit (ICU) admission, (iii) ventilatory support, (iv) hospitalisation, (v) hepatic impairment, (vi) ischaemic stroke, and (vii) myocardial infarction. Subgroup analyses included age (<70; ≥70 years); sex, Charlson comorbidity index (≤5; >5), and number of COVID-19 vaccine doses received (0-1; ≥2 doses). A total of 4886 patients were included (nirmatrelvir-ritonavir: 1462; molnupiravir: 3424). There were 347 events of all-cause mortality (nirmatrelvir-ritonavir: 74, 5.06%; molnupiravir: 273, 7.97%), 10 events of ICU admission (nirmatrelvir-ritonavir: 4, 0.27%; molnupiravir: 6, 0.18%), 48 events of ventilatory support (nirmatrelvir-ritonavir: 13, 0.89%; molnupiravir: 35, 1.02%), 836 events of hospitalisation (nirmatrelvir-ritonavir: 218, 23.98%; molnupiravir: 618, 28.14%), 1 event of hepatic impairment (nirmatrelvir-ritonavir: 0, 0%; molnupiravir: 1, 0.03%), 8 events of ischaemic stroke (nirmatrelvir-ritonavir: 3, 0.22%; molnupiravir: 5, 0.16%) and 9 events of myocardial infarction (nirmatrelvir-ritonavir: 2, 0.15%; molnupiravir: 7, 0.22%). Nirmatrelvir-ritonavir users had lower rates of all-cause mortality (absolute risk reduction (ARR) at 90 days 2.91%, 95% CI: 1.47-4.36%) and hospitalisation (ARR at 90 days 4.16%, 95% CI: 0.81-7.51%) as compared with molnupiravir users. Similar rates of ICU admission (ARR at 90 days-0.09%, 95% CI:-0.4 to 0.2%), ventilatory support (ARR at 90 days 0.13%, 95% CI:-0.45 to 0.72%), hepatic impairment (ARR at 90 days 0.03%, 95% CI:-0.03 to 0.09%), ischaemic stroke (ARR at 90 days-0.06%, 95% CI:-0.35 to 0.22%), and myocardial infarction (ARR at 90 days 0.07%, 95% CI:-0.19 to 0.33%) were found between nirmatrelvir-ritonavir and molnupiravir users. Consistent results were observed in relative risk adjusted with baseline characteristics. Nirmatrelvir-ritonavir was associated with significantly reduced risk of all-cause mortality (HR: 0.624, 95% CI: 0.455-0.857) and hospitalisation (HR: 0.782, 95% CI: 0.64-0.954). Patients with COVID-19 with advanced kidney disease receiving nirmatrelvir-ritonavir had a lower rate of all-cause mortality and hospital admission when compared with molnupiravir. Other adverse clinical outcomes were similar in both treatment groups. Health and Medical Research Fund (COVID1903010), Health Bureau, The Government of the Hong Kong Special Administrative Region, China.

Vasoactive Management of Pulmonary Hypertension and Ventricular Dysfunction in Neonates Following Complicated Monochorionic Twin Pregnancies: A Single-Center Experience.

Twins resulting from a complicated monochorionic (MC) twin pregnancy are at risk for postnatal evolution of pulmonary hypertension (PH) and cardiac dysfunction (CD). Both pathologies are important contributors to short- and long-term morbidity in these infants. The aim of the present retrospective single-center cohort study was to evaluate the need for vasoactive treatment for PH and CD in these neonates. In-born neonates following a complicated MC twin pregnancy admitted to the department of neonatology of the University Children's Hospital Bonn (UKB) between October 2019 and December 2023 were screened for study inclusion. Finally, 70 neonates were included in the final analysis, with 37 neonates subclassified as recipient twins (group A) and 33 neonates as donor twins (group B). The overall PH incidence at day of life (DOL) 1 was 17% and decreased to 6% at DOL 7 (p = 0.013), with no PH findings at DOL 28. The overall incidence of CD was 56% at DOL 1 and decreased strongly until DOL 7 (10%, p = 0.015), with no diagnosis of CD at DOL 28. The use of dobutamine, norepinephrine, and vasopressin at DOL 1 until DOL 7 did not differ between the subgroups, whereas the dosing of milrinone was significantly higher in Group B at DOL 1 (p = 0.043). Inhaled nitric oxide (iNO) was used in 16% of the cohort, and a levosimendan therapy was administered in 34% of the neonates. One-third of the cohort was treated with oral beta blockers, and in 10%, an intravenous beta blockade (landiolol) was administered. The maximum levosimendan vasoactive-inotropic score (LVISmax) increased from DOL 1 (12.4 [3/27]) to DOL 2 (14.6 [1/68], p = 0.777), with a significant decrease thereafter as measured at DOL 7 (9.5 [2/30], p = 0.011). Early PH and CD are frequent diagnoses in neonates following a complicated MC twin pregnancy, and an individualized vasoactive treatment strategy is required in the management of these infants.

Beta blockers are associated with lower all-cause mortality among HFpEF patients.

The evidence regarding beta blocker (BB) benefit in heart failure with preserved ejection fraction (HFpEF) remains inconclusive, leading to consideration of BB withdrawal in this population. In this study, we retrospectively analyzed the association of BB on all-cause mortality in HFpEF patients. This is a single-center retrospective cohort study of 20,206 patients with left ventricular ejection fraction (EF) ≥ 50% who were hospitalized with decompensated HF between January 2011 and March 2020. Survival is reported at 30days, 1year, and 3years. A secondary analysis comparing mortality for patients on BB with additional indications including hypertension (HTN), coronary artery disease (CAD), and atrial fibrillation (AF) was completed. Mortality was compared between patients on BB and additional therapies of spironolactone or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs). BB showed lower all-cause mortality at 30days, 1year, and 3years (p < 0.0001). This association with lower all-cause mortality was validated by a supplementary propensity score-matched analysis. At 3years, there was significant mortality reduction with addition of BB to either spironolactone (p = 0.0359) or ACEi/ARBs (p < 0.0001). In a large single-center retrospective registry, BB use was associated with lower mortality in HFpEF patients with a recent decompensated HF hospitalization. The mortality benefit persisted in those treated with spironolactone or ACEi/ARBs, and in those with AF. This provocative data further highlights the uncertainty of the benefit of BB use in this cohort and calls for re-consideration of BB withdrawal, especially in those tolerating it well, without conclusive, large, and randomized trials showing lack of benefit or harm.

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.

ANTIHYPERTENSIVE DRUGS IN CHRONIC HEART FAILURE IN THE CZECH REPUBLIC, FOCUSING ON BETA-BLOCKERS

Objective: Hypertension is a very common comorbidity in patients with heart failure. Beta-blockers (BB) are the first choice drug together with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) in patients with heart failure with reduced left ventricular ejection fraction (HFrEF), reducing morbidity and mortality. Design and method: Data were collected in the FARmacology and NeuroHumoral Activation Registry (FAR NHL). Patients with chronic heart failure with left ventricular ejection fraction (LVEF) &lt; 50% for at least one month were included. Results: 1,100 patients with a mean age of 65 years, 80.8% male, were included. The mean systolic blood pressure was 128.0 mm Hg, mean diastolic blood pressure was 80.0 mm Hg. Of all patients, 20% received low dose of beta-blocker (LD), 57% medium dose (MD) and 17% high dose (HD), 6.2% did not receive BB. The higher the blood pressure (LD 124/ 77; MD 129/ 80; HD 132/ 82 mm Hg; p &lt; 0.001), LV EF (LD 29.5; MD 30.5; HD 32.0%; p = 0.003), creatinine clearance (LD 78.7; MD 87.8; HD 91.1 ml/min; p = 0.001) or weight of the patients, the higher the BB dose they received (LD 83.2; MD 88.7; HD 93.5 kg; p &lt; 0.001). The lower the NT-proBNP, the higher the BB dose patients received (LD 767; MD 456; HD 314 pg/ml; p &lt; 0.001). The presence of atrial fibrillation (AF) did not affect the BB dose. Patients with AF were more likely to be treated with digoxin or a combination of digoxin and BB than patients without AF (p &lt; 0.001). Conclusions: According to FAR NHL registry, almost 94% of patients with HFrEF receive BB. A total of 17% of patients take the target dose of BB. If a patient has BB, he/she is treated with the recommended preparation in more than 99% of cases. The more severe the disease, as reflected by lower BP, creatinine clearance, LV EF, weight or higher NT-proBNP, the lower the dose of beta-blockers the patient receives and tolerates.