Use Of Β-blockers Research Articles

Association of Premature Ventricular Contraction Burden on Serial Holter Monitoring With Arrhythmic Risk in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

A high burden of premature ventricular contractions (PVCs) at disease diagnosis has been associated with an overall higher risk of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC). Data regarding dynamic modification of PVC burden at follow-up with Holter monitoring and its impact on arrhythmic risk in ARVC are scarce. To describe changes in the PVC burden and to assess whether serial Holter monitoring is dynamically associated with sustained ventricular arrhythmias during follow-up in patients with ARVC. In this cohort study, patients with a definite ARVC diagnosis, available Holter monitoring results at disease diagnosis, and at least 2 additional results of Holter monitoring during follow-up were enrolled from 6 ARVC registries in North America and Europe. Data were collected from June 1 to September 15, 2021. The association between prespecified variables retrieved at each Holter monitoring follow-up (ie, overall PVC burden; presence of sudden PVC spikes, defined as absolute increase in PVC burden ≥5000 per 24 hours or a relative ≥75% increase, with an absolute increase of ≥1000 PVCs; presence of nonsustained ventricular tachycardia [NSVT]; and use of β-blockers and class III antiarrhythmic drugs) and sustained ventricular arrhythmias occurring within 12 months after that Holter examination was assessed using a mixed logistical model. In 169 enrolled patients with ARVC (mean [SD] age, 36.3 [15.0] years; 95 men [56.2%]), a total of 723 Holter examinations (median, 4 [IQR, 4-5] per patient) were performed during a median follow-up of 54 (IQR, 42-63) months and detected 75 PVC spikes and 67 sustained ventricular arrhythmias. The PVC burden decreased significantly from the first to the second Holter examination (mean, 2906 [95% CI, 1581-4231] PVCs per 24 hours; P < .001). A model including 24-hour PVC burden (odds ratio [OR] 1.50 [95% CI, 1.10-2.03]; P = .01), PVC spikes (OR, 6.20 [95 CI, 2.74-13.99]; P < .001), and NSVT (OR, 2.29 [95% CI, 1.10-4.51]; P = .03) at each follow-up Holter examination was associated with sustained ventricular arrhythmia occurrence in the following 12 months. These findings suggest that in patients with ARVC, changes in parameters derived from each Holter examination performed during follow-up are associated with the risk of sustained ventricular arrhythmias within 12 months of disease diagnosis.

Blood-brain barrier permeable β-blockers linked to lower risk of Alzheimer's disease in hypertension.

Alzheimer's disease is a neurodegenerative disorder in which the pathological accumulation of amyloid-β and tau begins years before symptom onset. Emerging evidence suggests that β-blockers (β-adrenergic antagonists) increase brain clearance of these metabolites by enhancing CSF flow. Our objective was to determine whether β-blocker treatments that easily cross the blood-brain barrier reduce the risk of Alzheimer's disease compared to less permeable β-blockers. Data from the Danish national registers were used to identify a retrospective cohort of individuals with hypertension, and those treated with β-blockers were included in the analysis. People with indications for β-blocker use other than hypertension (e.g. heart failure) were only retained in a sensitivity analysis. β-blockers were divided into three permeability groups: low, moderate and high. We used multivariable cause-specific Cox regression to model the effect of β-blocker blood-brain barrier permeability on time to dementia outcomes, adjusting for baseline comorbidities, demographics and socioeconomic variables. Death was modelled as a competing risk. The 10-year standardized absolute risk was estimated as the averaged person-specific risks per treatment. In a cohort of 69 081 (median age = 64.4 years, 64.8% female) people treated with β-blockers for hypertension, highly blood-brain barrier-permeable β-blockers were associated with reduced risk of Alzheimer's disease versus low permeability β-blockers (-0.45%, P < 0.036). This effect was specific to Alzheimer's diagnoses and did not extend to dementia in general. Propensity score analysis matching high and low blood-brain barrier-permeable patients also detected a decreased Alzheimer's risk (-0.92%, P < 0.001) in the high permeability group compared to the low, as did a 1-year landmark analysis (-0.57%, P < 0.029) in which events within the first year of follow-up were ignored as likely unrelated to treatment. Our results suggest that amongst people taking β-blockers for hypertension, treatment with highly blood-brain barrier permeable β-blockers reduces the risk of Alzheimer's disease compared to low permeability drugs. Our findings support the hypothesis that highly permeable β-blockers protect against Alzheimer's disease by promoting waste brain metabolite clearance.

Cardiorespiratory Fitness, BMI, Mortality, and Cardiovascular Disease in Adults with Overweight/Obesity and Type 2 Diabetes.

We estimated the effects of cardiorespiratory fitness (CRF) and body mass index (BMI) at baseline on mortality and cardiovascular disease events in people with type 2 diabetes who participated in the Look AHEAD randomized clinical trial. Look AHEAD compared effects of an intensive lifestyle intervention with diabetes support and education on cardiovascular disease events in 5145 adults age 45-76 yr with overweight/obesity and type 2 diabetes. In 4773 participants, we performed a secondary analysis of the association of baseline CRF during maximal treadmill test (expressed as metabolic equivalents (METs)) on mortality and cardiovascular disease events during a mean follow-up of 9.2 yr. The mean (SD) CRF was 7.2 (2.0) METs. Adjusted for age, sex, race/ethnicity, BMI, intervention group, and β-blocker use, all-cause mortality rate was 30% lower per SD greater METs (hazard ratio (HR) = 0.70 (95% confidence interval, 0.60 to 0.81); rate difference (RD), -2.71 deaths/1000 person-years (95% confidence interval, -3.79 to -1.63)). Similarly, an SD greater METs predicted lower cardiovascular disease mortality (HR, 0.45; RD, -1.65 cases/1000 person-years) and a composite cardiovascular outcome (HR, 0.72; RD, -6.38). Effects of METs were homogeneous on the HR scale for most baseline variables and outcomes but heterogeneous for many on the RD scale, with greater RD in subgroups at greater risk of the outcomes. For example, all-cause mortality was lower by 7.6 deaths/1000 person-years per SD greater METs in those with a history of cardiovascular disease at baseline but lower by only 1.6 in those without such history. BMI adjusted for CRF had little or no effect on these outcomes. Greater CRF is associated with reduced risks of mortality and cardiovascular disease events.

Cardioselective Versus Nonselective β-Blockers After Myocardial Infarction in Adults With Chronic Obstructive Pulmonary Disease

ObjectiveTo investigate which types of β-blockers have better efficacy and safety profiles in patients with concomitant chronic obstructive pulmonary disease (COPD) and myocardial infarction (MI) to address concerns about use of β-blockers in COPD. MethodsWe identified 65,699 patients with COPD prescribed β-blockers after first MI in the Taiwan National Health Insurance Research Database between January 1, 2001, and December 31, 2013. Comparisons were performed using the inverse probability of treatment weighting method. The primary outcome was all-cause mortality; secondary outcomes were heart failure hospitalization, major adverse cardiac and cerebrovascular event (MACCE), and major adverse pulmonary event (MAPE). ResultsA total of 14,789 patients prescribed β-blockers were enrolled, of whom 7247 (49.0%) used cardioselective β-blockers and 7542 (51.0%) used nonselective β-blockers. The cardioselective group had lower incidence rates of mortality (hazard ratio [HR], 0.93; 95% CI, 0.89 to 0.96), MACCE (HR, 0.96; 95% CI, 0.93 to 0.998), heart failure hospitalization (subdistribution HR, 0.84; 95% CI, 0.78 to 0.91), and MAPE (HR, 0.94; 95% CI, 0.90 to 0.98) at the end of follow-up after weighting. Similar results were also found in subgroup analysis between those prescribed bisoprolol and those prescribed carvedilol. ConclusionPatients prescribed a cardioselective β-blocker may have a lower incidence of all-cause mortality, MACCE, heart failure hospitalization, and MAPE than those prescribed a nonselective β-blocker. Cardioselective β-blocker treatment during hospitalization and continuing after discharge appears to be superior to nonselective β-blocker treatment in patients with COPD after MI.

Періопераційне застосування β-адреноблокаторів у пацієнтів високого ризику

Незважаючи на краще розуміння того, які бувають передвісники розвитку хронічної серцевої недостатності та які сигнальні системи лежать в основі її патофізіології, а також покращення результатів терапії, значна кількість пацієнтів, особливо похилого віку, не отримують ефективного лікування. Пацієнти похилого віку з такою патологією зазвичай вимагають додаткового об’єму діагностики й значного розширення спектра анестезіологічних заходів у відділеннях інтенсивної терапії. Анестезіологи мають потребу в удосконаленні періопераційного знеболювання при проведенні оперативних втручань. Препарати групи β-адреноблокаторів для лікування пері­операційної гіпертензії, ішемії й аритмій призначаються в передопераційному періоді в групі пацієнтів, які раніше не отримували такого лікування. Періопераційне призначення β-адреноблокаторів у пацієнтів високого ризику використовується недостатньо. Проте питання про те, чи мають β-адреноблокатори знову застосовуватись у передопераційному періоді виключно для запобігання негативним наслідкам хронічної серцевої недостатності, залишається вельми дискутабельним.

Association of renin-angiotensin-aldosterone system inhibition with Covid-19 hospitalization and all-cause mortality in the UK biobank.

With growing evidence on the protective effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in coronavirus disease 2019 (Covid-19), we aimed to thoroughly investigate the association between the use of major classes of antihypertensive medications and Covid-19 outcomes in comparison with the use of ACEIs and ARBs. We conducted a population-based study in patients with pre-existing hypertension in the UK Biobank with data from the first 2 SARS-CoV-2 waves prior population-based vaccination. Multivariable logistic regression analysis was performed adjusting for a wide range of confounders. The use of either β-blockers (BBs), calcium-channel blockers (CCBs) or diuretics was associated with a higher risk of Covid-19 hospitalization compared to ACEI use (adjusted OR (95%CI): 1.66 [1.43-1.93]) and ARB use (1.53 [1.30-1.81]). The risk of 28-day mortality among Covid-19 patients was also increased among users of BBs, CCBs or diuretics when compared to ACEI users (1.74 [1.30-2.33]) but not when compared to ARB users (1.26 [0.93-1.71]). The association between BB, CCB or diuretic use (compared to ACEI use) and 28-day mortality among hospitalized Covid-19 patients narrowly missed statistical significance (1.47 [0.99-2.18]) but it was statistically significant when the analysis was restricted to patients hospitalized during the second SARS-CoV-2 wave (1.80 [1.15-2.83]). Our results suggest protective effects of inhibition of the renin-angiotensin-aldosterone system on Covid-19 hospitalization and mortality, particularly with ACEI, among patients with pharmaceutically treated hypertension. If confirmed by randomized controlled trials, this finding could have high clinical relevance for treating hypertension during the SARS-CoV-2 pandemic.

Association of β-Blocker Use at Time of Radical Prostatectomy With Rate of Treatment for Prostate Cancer Recurrence

The perioperative period has gained attention as a window of opportunity to prevent cancer recurrence. Evidence in support of a role for nonselective β-blockers (nsBBs) in cancer treatment is increasing, and counteracting cancer recurrence associated with perioperative stress and catecholamine is one of the suggested mechanisms of action. To explore whether use of nsBBs at the time of radical prostatectomy is associated with a lower rate of treatment for prostate cancer recurrence. This cohort study analyzed prospectively collected data from the Cancer Registry of Norway, Norwegian Patient Registry, Norwegian Prescription Database, and Norwegian Cause of Death Registry. Of 12 298 eligible patients, this study included 11 117 treatment-naive patients with prostate cancer (ie, no prior hormonal therapy, radiotherapy, or chemotherapy) who underwent radical prostatectomy in Norway from January 1, 2008, to December 31, 2015, with a minimum progression-free follow-up of 6 months. Data analysis was performed from April 20, 2020, to April 30, 2021. Use of nsBBs and selective β-blockers (sBBs) at time of radical prostatectomy. Treatment for cancer recurrence after radical prostatectomy (defined as initiation of hormonal therapy, radiotherapy, or chemotherapy) or, if no treatment was identified, cancer-specific mortality. The study included 11 117 men with prostate cancer (median [IQR] age at radical prostatectomy, 64.8 [60.4-68.3] years). Of these, 1622 (14.6%) later received treatment for cancer recurrence during a median follow-up of 4.3 years (IQR, 2.4-6.3 years). Use of nsBBs at time of surgery among 209 patients was significantly associated with a lower risk of treatment for cancer recurrence (adjusted hazard ratio [aHR], 0.64; 95% CI, 0.42-0.96; P = .03). No such association was observed for use of sBBs (aHR, 0.96; 95% CI, 0.84-1.11; P = .62). Subanalyses with (1) relaxed inclusion criteria allowing for inclusion also of patients with early progression (within 6 months) and (2) only the healthiest patients (Eastern Cooperative Oncology Group performance status of 0) supported the main findings. In this cohort study, use of nsBB but not sBBs at the time of radical prostatectomy was associated with less treatment initiation for cancer recurrence. This finding, together with accumulated preclinical and clinical evidence, provides a foundation for initiation of an interventional study.

Genetic risk of hyperuricemia in hypertensive patients associated with antihypertensive drug therapy: A longitudinal study.

Elevated serum uric acid (UA) level has been shown to be influenced by multiple genetic variants, but it remains uncertain how UA‐associated variants differ in their influence on hyperuricemia risk in people taking antihypertensive drugs. We examined a total of 43 UA‐related variants at 29 genes in 1840 patients with hypertension from a community‐based longitudinal cohort during a median 2.25‐year follow‐up (including 1031 participants with normal UA, 440 prevalent hyperuricemia at baseline, and 369 new‐onset hyperuricemia). Compared with the wild‐type genotypes, patients carrying the SLC2A9 rs3775948G allele or the rs13129697G allele had decreased risk of hyperuricemia, while patients carrying the SLC2A9 rs11722228T allele had increased risk of hyperuricemia, after adjustment for cardiovascular risk factors and correction for multiple comparisons; moreover, these associations were modified by the use of diuretics, β‐blockers, or angiotensin converting enzyme inhibitors. The rs10821905A allele of A1CF gene was associated with increased risk of hyperuricemia, and this risk was enhanced by diuretics use. The studied variants were not observed to confer risk for incident cardiovascular events during the follow‐up. In conclusion, the genes SLC2A9 and A1CF may serve as potential genetic markers for hyperuricemia risk in relation to antihypertensive drugs therapy in Chinese hypertensive patients.

β-Blockers and the Risk of Depression: A Matched Case-Control Study.

IntroductionDepression is a commonly cited adverse effect of β-blockers but the evidence for a causal relationship is limited.ObjectiveWe aimed to explore whether β-blockers are associated with an increased risk of new-onset depression.MethodsWe conducted a case–control study using the UK population-based Clinical Practice Research Datalink (CPRD) GOLD. We identified patients aged 18−80 years with an incident depression diagnosis between 2000 and 2016, and matched controls, and estimated the risk (odds ratio [OR]) of depression in association with use of β-blockers. We also conducted analyses of exposure, categorised by number and timing of prescriptions and by indication for β-blocker use.ResultsThe study encompassed 118,705 patients with incident depression and the same number of matched controls. The odds of developing depression were increased for current short-term use of any β-blocker (adjusted OR [aOR] 1.91, 95% confidence interval [CI] 1.72−2.12), whereas current long-term use was not associated with the risk of depression compared with never use. The elevated risk of depression among short-term users was mostly confined to propranolol users with a neuropsychiatric disorder (aOR 6.33, 95% CI 5.16–7.76), while propranolol users with a cardiovascular indication were only at marginally increased risk of depression (aOR 1.44, 95% CI 1.14–1.82).ConclusionsThis study suggests that the association between use of β-blockers and depression may not be causal but rather a result of protopathic bias. Propranolol is often prescribed to treat neuropsychiatric symptoms, suggesting that the onset of depression may be related to the underlying indication rather than to an effect of a β-blocker therapy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01140-5.

Comparative Pharmacotherapy of Hypertension

The purpose of the study. This study aims to review the practice of the utilization of antihypertensive drugs of various pharmacological groups within the condition of the therapeutic hospital in Ukrainian and Egyptian patients, adherence to treatment in patients with hypertension in Ukraine and Egypt. Materials and methods. A study of 120 patients who were treated for hypertension II stage in a therapeutic hospital in Ternopil and Cairo was conducted. All subjects completed a questionnaire that included personal, socio-demographic, and medical data. The number and type of hypotensive drugs or drug combinations were analyzed. Results and discussion. Regarding the pharmacotherapy of hypertension the use of β-blockers among Ukrainian participants did not differ from Egyptian. The use of calcium channel antagonists was a little bit higher among Egyptians than Ukrainians. Diuretics were used more often by Ukrainians than by Egyptians. The use of ACEI/ARBs surpassed the use of all other classes of antihypertensives among both groups. Whereas the ACEI/ARBs use among Egyptians was lower than Ukrainians. In this study we conducted a determination of compliance which was defined as an act of adhering to the regimen of care recommended by the clinician and persisting with it over time. The majority of Ukrainian and Egyptian patients with hypertension do not always perform the doctor's prescription. The reason for the unfull implementation of medical prescriptions with the same frequency was called deficiency of funds and forgetfulness. Near 80% of Ukrainian respondents are ready to complete the prescription with understanding, however, 14% of the patients stated that they were not always ready to fulfill the prescription, and the smallest part of patients did not think it was necessary to follow the regularity of treatment and treatment regimen. We noted no significant difference in the adherence to antihypertensive therapy between Ukrainian and Egyptian participants. Early discontinuation of treatment and suboptimal daily use of the prescribed regimens are the foremost common facets of poor adherence to treatment as well as non-adherence to antihypertensive therapy correlates with a better risk of cardiovascular events. Conclusion. ACEI/ARBs are the most commonly used group of antihypertensive drugs among Ukrainian and Egyptian patients. The majority of Ukrainian and Egyptian participants with hypertension do not always perform the doctor's prescription. Only 50% had an objective reason for insufficient compliance

ANALYSIS OF MEDICAL PURPOSES ANDPRICE AVAILABILITY OF THE ASSORTMENT OF BETA-ADRENOBLOCKERS USED FOR THE TREATMENT OF MYOCARDIAL INFARCTION

Patients who have had myocardial infarction (MI) represent a group of patients with a very high risk of cardiovascular complications: first of all, recurrent myocardial infarction, chronic heart failure and cardiovascular death. Clinical studies have shown an increase in life expectancy after MI when prescribing selective β-blockers for long-term prophylaxis, especially in the presence of chronic heart failure complicating the course of MI. The main clinical goals of prescribing β-blockers are to improve the supply of oxygen to the myocardium and to prevent the development of life-threatening cardiac arrhythmias. In view of the above, drugs in this group should be used indefinitely in patients with MI [7]. In recent years, the analysis of the affordability of the use of treatment technologies, including for cardiovascular diseases (CVD), has stood out as a serious scientific area with its methodology, scientific tools and is currently an important source of information that helps in making management decisions in healthcare [3.6]. The purpose of this article was to conduct such an analysis in relation to the use of β-blockers in MI in Kuzbass.

Not Baseline Atrial Fibrillation but New-Onset Atrial Fibrillation and the Loss of Left Atrial Function Are Essential for Predicting Poor Outcomes in Non-ischemic Cardiomyopathy.

Aims: The clinical impact of the type of atrial fibrillation (AF) has not been completely elucidated in non-ischemic cardiomyopathy (NICM). Although the structure and function of the left atrium (LA) provide prognostic information in patients with heart failure, the relationship of the AF type with LA structure and function in NICM is unclear.Methods: Consecutive patients with NICM who underwent cardiac magnetic resonance were evaluated and followed. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for major adverse cardiovascular events (MACE) related to the AF type, such as paroxysmal AF, chronic AF, and new-onset AF (NOAF).Results: Among 625 patients with NICM (mean age, 64.4 ± 14.2 years; women, 39.7%), 133 had a history of AF at baseline; of these, 60 had paroxysmal AF. Each baseline AF type was associated with higher LA volume and lower LA emptying fraction but not with an increased incidence of MACE (p = 0.245). New-onset AF developed in 5.9% of patients with sinus rhythm over a median follow-up period of 609 days, and maximum LA volume was a strong and independent predictor [p < 0.001, area under the ROC curve (AUC): 0.795]. Maximum LA volume was superior to LA emptying fraction and B-type natriuretic peptide (AUC: 0.683 and 0.680, respectively). The use of β-blocker and the age of the patient were associated with the incidence of NOAF (HR: 0.37, 95% CI: 0.16–0.84 and HR: 1.05, 95% CI: 1.01–1.09, respectively). Kaplan–Meier analysis showed that patients with NOAF had a higher incidence of MACE than those with sinus rhythm or baseline AF (p = 0.002). NOAF and LA emptying fraction were independent predictors of MACE (HR: 2.28, 95% CI: 1.20–3.97 and HR: 0.98, 95% CI: 0.96–0.99, respectively) after adjusting for age, sex, body mass index, and diagnosis.Conclusions: Paroxysmal and chronic AF in patients with NICM were not associated with an increased incidence of MACE despite their association with LA volume and function. NOAF was independently associated with poor prognosis. Higher maximum LA volume predicted the onset and lower LA emptying fraction was independently associated with poor prognosis.

Usefulness of Restless Legs Symptoms to Predict Adverse Cardiovascular Outcomes in Men With Coronary Artery Disease

The relationship between restless legs syndrome (RLS) and cardiovascular disease remains enigmatic in the general population, and its prognostic value in patients with coronary artery disease (CAD) is unknown. In this study, the frequency of RLS-like symptoms was assessed using a validated instrument in 3,266 patients undergoing cardiac catheterization (mean age 64 years, 62% male, 23% Black, and 74% with obstructive CAD). Patients were followed for primary end points of cardiovascular death or incident myocardial infarction. Fine and Gray hazard models explored the association between RLS and incident events after adjustment for demographic and clinical risk factors. In the total cohort, 29% of patients reported mild (rare or sometimes) symptoms, and 15% of patients had moderate/severe (often to almost always) symptoms of RLS. Female sex (odds ratio [OR] 2.11, 95% confidence interval (CI), 1.68 to 2.57), body mass index (OR 1.12 per 5 kg/m2, 95% CI, 1.04 to 1.22), diabetes (OR 1.43, 95%,1.15 to 1.79), and β-blocker use (OR 1.35, 95% CI, 1.07 to 1.72) were independently associated with moderate/severe symptoms of RLS compared with no symptoms. Over a 5-year follow-up period, 991 patients suffered an adverse event. Compared with those with no symptoms, patients with moderate/severe RLS had significantly higher risk of the primary end point (hazard ratio [HR]=1.33, 95%),CI 1.01 to 1.76) after adjustment for demographic and clinical risk factors. The association was more significant in men than women, HR 1.98, 95% CI, 1.41 to 2.78 versus HR 0.99 (,95% CI, 0.64 to 1.52, p interaction= 0.013. In conclusion, among men with CAD, moderate-to-severe symptoms of RLS are associated with significantly higher risk of adverse cardiovascular outcomes, independent of traditional risk factors.

The Role of Ivabradine in Managing Symptomatic Patients with Chronic Coronary Syndromes: A Clinically Oriented Approach

Angina is a significant contributor to disability and impairment in quality of life in patients with chronic coronary syndromes (CCS). An elevated heart rate (HR) may trigger myocardial ischemia by increasing oxygen consumption and decreasing the diastolic time, compromising the coronary flow. HR-lowering strategies offer symptom control and prevent cardiovascular events in subgroups of patients with CCS. However, the best therapeutic approach to achieve the desired HR in patients with CCS can be challenging based on efficacy and tolerability. Guidelines usually propose β-blockers and/or non-dihydropyridine calcium channel blockers (CCB) for angina patients with elevated HR. Nonetheless, there is no clear evidence of greater antianginal efficacy of this strategy versus an alternative HR-lowering agent. Ivabradine reduces the HR by blocking the If current in the sinoatrial node without affecting myocardial contractility or vascular tone. The magnitude of the HR reduction by ivabradine is proportional to the initial HR, which decreases the risk of significant bradycardia. Ivabradine increases the diastolic time and the coronary flow reserve to a greater extent than β-blockers and favors collateralization, improving the regional blood flow. We present two clinical cases of patients with symptomatic CCS in whom HR control with ivabradine was fundamental for symptom control and improvement in left ventricular (LV) function. An earlier combination of ivabradine plus β-blockers would have provided more rapid symptom control and improved LV function in the first case. In the second case, the primary mechanism responsible for angina was most likely a coronary vasomotor abnormality, in which the use of β-blockers aggravated the discomfort. The combination of a dihydropyridine CCB plus ivabradine was highly influential in symptom control. Due to its effects beyond HR reduction and good tolerability, ivabradine should be considered an essential ally in managing patients with angina and high HR with or without LV dysfunction. Talking Head Video (MP4 77394 kb)Supplementary InformationThe online version contains supplementary material available at 10.1007/s40119-021-00247-1.

Relationship Between Heart Rate at Discharge and Long-Term Outcomes of Surgically Treated Patients With Type A Acute Aortic Dissections.

Resting heart rate (HR) at discharge is an important predictor of mortality after acute myocardial infarction. However, in patients with Stanford type A acute aortic dissections (TA-AADs), the relationship between HR and long-term outcomes is unclear. Therefore, this relationship was investigated in the present study. Surgically treated consecutive patients with TA-AAD (n=721) were retrospectively categorized according to HR quartiles, recorded within 24 h before discharge (<70, 70-77, 78-83, and ≥84 beats/min). The study endpoints included aortic aneurysm-related deaths, sudden deaths, aortic surgeries, and hospitalizations for recurrence of acute aortic dissections. The mean (±SD) patient age was 65.8±13.0 years. During a median observation period of 5.8 years (interquartile range 3.9-8.5 years), 17.2% of patients (n=124) experienced late aortic events. Late aortic surgery was performed in 14.0% of patients. After adjusting for potential confounders, including β-blocker use, HR at discharge remained an independent predictor of long-term aortic outcomes. Patients with discharge HR ≥84 beats/min had a higher risk (hazard ratio 1.86; 95% confidence interval 1.06-3.25; P=0.029) of long-term aortic events than those with HR <70 beats/min; the cumulative survival rates were similar among the groups (log-rank, P=0.905). In surgically treated patients with TA-AAD, HR at discharge independently predicted long-term aortic outcomes. Consequently, HR in patients with TA-AAD should be optimized before discharge, particularly if the HR is ≥84 beats/min.

Long-term impact of β-blocker in elderly patients without myocardial infarction after percutaneous coronary intervention.

AimsLittle is known about the long‐term outcomes of β‐blockers use in patients with coronary artery disease (CAD) without myocardial infarction (MI) and reduced ejection fraction (rEF). However, more attention should be paid to the oral administration of β‐blockers in elderly patients who are susceptible to heart failure (HF), sinus node dysfunction, or rate response insufficiency. We aimed to evaluate the long‐term impact of β‐blockers in elderly patients with CAD without MI or systolic HF who have undergone percutaneous coronary intervention.Methods and resultsA total of 1018 consecutive elderly patients with CAD (mean age, 72 ± 7 years; 77% men) who underwent their first intervention between 2010 and 2018 were included in this study. According to the presence or absence of the use of β‐blockers, 514 patients (50.5%) were allocated to the β‐blocker group, and 504 (49.5%) to the non‐β‐blocker group. We evaluated the incidence of 4‐point major adverse cardiovascular events (4P‐MACE), including cardiovascular death, non‐fatal MI, non‐fatal stroke, admission for HF, target vessel revascularization (TVR), and all‐cause death. We focused on the association between chronotropic incompetence of β‐blockers and incidence of a new HF and analysed the results using an exercise electrocardiogram regularly performed in the outpatient department after percutaneous coronary intervention. During a median follow‐up duration of 5.1 years, 83 patients (8.3%) developed 4P‐MACE, including cardiovascular death in 17, non‐fatal MI in 13, non‐fatal stroke in 25, and admission for HF in 39 patients. Additionally, 124 patients (12.2%) had a TVR and 104 (10.2%) died of other causes. Kaplan–Meier analysis showed that the cumulative incidence rate of 4P‐MACE in the β‐blocker group was significantly higher than that in the non‐β‐blocker group (15.4% vs. 10.0%, log‐rank test, P = 0.015). Above all, the cumulative incidence rate of admission for HF in the β‐blocker group was significantly higher (8.8% vs. 3.2%, log‐rank test, P < 0.001). The β‐blocker group had significantly lower resting heart rate, stress heart rate, and stress‐rest Δ heart rate on exercise electrocardiogram. Multivariate Cox hazard analysis revealed that EF, β‐blocker use, stress‐rest Δ heart rate, and CKD were strong independent predictors of admission for HF.ConclusionsLong‐term β‐blocker use was significantly associated with an increased risk of adverse cardiovascular events in elderly patients with CAD without MI or systolic HF. In particular, the chronotropic incompetence action of β‐blockers could increase the risk of admission for HF in elderly patients with CAD without MI and systolic HF, and the present findings warrant further investigation.

Impact of Left Atrial Appendage Amputation on Left Atrial Morphology and Rhythm after Off-Pump CABG.

Left atrial appendage (LAA) amputation concomitant to coronary artery bypass grafting (CABG) has become an increasingly performed technique in patients with atrial fibrillation (AF) or with sinus rhythm and a CHA2DS2-VASc score ≥2. However, LAA amputation has come under suspicion to cause postoperative atrial fibrillation (POAF) due to left atrial (LA) dilation. This study aims to assess this assumption in patients undergoing CABG in off-pump technique with and without amputation of the LAA. Patients who underwent isolated CABG in off-pump technique without history of AF were retrospectively examined. Cohorts were divided according to the concomitant execution of LAA amputation. LA volume was measured by transthoracic echocardiography and rhythm was analyzed by electrocardiography, medication protocol, and visit documentation. Propensity score (PS) matching was performed based on 20 preoperative risk variables to correct for selection bias. A total of 1,522 patients were enrolled, with 1,267 in the control group and 255 in the LAA amputation group. Occurrence of POAF was compared in 243 PS-matched patient pairs. Neither the unmatched cohort (odds ratio [OR] 0.82; 95% confidence interval or CI [0.61; 1.11], p = 0.19) nor the PS-matched cohort (OR 0.94; 95% CI [0.62; 1.41], p = 0.75) showed significant differences in POAF occurrence. Subgroup analysis of sex, use of β-blockers, pulmonary disease, ejection fraction, and CHA2DS2-VASc-Score also showed no tendencies. LA volume did not change significantly (p = 0.18, 95% CI [-0.29; 1.51]). Surgical amputation of the LAA concomitant to CABG did not lead to LA dilation and has no significant impact on the occurrence of POAF.

Extracellular Matrix in Heart Failure: Role of ADAMTS5 in Proteoglycan Remodeling.

Remodeling of the extracellular matrix (ECM) is a hallmark of heart failure (HF). Our previous analysis of the secretome of murine cardiac fibroblasts returned ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) as one of the most abundant proteases. ADAMTS5 cleaves chondroitin sulfate proteoglycans such as versican. The contribution of ADAMTS5 and its substrate versican to HF is unknown. Versican remodeling was assessed in mice lacking the catalytic domain of ADAMTS5 (Adamts5ΔCat). Proteomics was applied to study ECM remodeling in left ventricular samples from patients with HF, with a particular focus on the effects of common medications used for the treatment of HF. Versican and versikine, an ADAMTS-specific versican cleavage product, accumulated in patients with ischemic HF. Versikine was also elevated in a porcine model of cardiac ischemia/reperfusion injury and in murine hearts after angiotensin II infusion. In Adamts5ΔCat mice, angiotensin II infusion resulted in an aggravated versican build-up and hyaluronic acid disarrangement, accompanied by reduced levels of integrin β1, filamin A, and connexin 43. Echocardiographic assessment of Adamts5ΔCat mice revealed a reduced ejection fraction and an impaired global longitudinal strain on angiotensin II infusion. Cardiac hypertrophy and collagen deposition were similar to littermate controls. In a proteomics analysis of a larger cohort of cardiac explants from patients with ischemic HF (n=65), the use of β-blockers was associated with a reduction in ECM deposition, with versican being among the most pronounced changes. Subsequent experiments in cardiac fibroblasts confirmed that β1-adrenergic receptor stimulation increased versican expression. Despite similar clinical characteristics, patients with HF treated with β-blockers had a distinct cardiac ECM profile. Our results in animal models and patients suggest that ADAMTS proteases are critical for versican degradation in the heart and that versican accumulation is associated with impaired cardiac function. A comprehensive characterization of the cardiac ECM in patients with ischemic HF revealed that β-blockers may have a previously unrecognized beneficial effect on cardiac chondroitin sulfate proteoglycan content.

Abstract 12351: Perioperative Interventions for Prevention of Postoperative Atrial Fibrillation After Cardiac Surgery: A Systematic Review and Network Meta-Analysis

Background: Postoperative atrial fibrillation (POAF) is the most common complication of cardiac surgery, which increases the risk of stroke and death, the length of hospital stays, and costs. Guidelines recommendations on the use of β-blockers (BBs) have only a modest influence on overall rates of POAF. The key clinical outcomes such as stroke and death have not been improved. The best approach to prophylaxis remains obscure. Method: We used Bayesian network meta-analysis to synthesize evidences from randomized controlled trials (RCTs) that compared interventions for POAF prophylaxis. The primary outcomes were incidence of POAF hypotension and bradycardia. Results: We included 262 RCTs with 52636 participants (age &gt; 18, undergoing CABG, valvular or combined surgery), in which 14 different interventions were investigated. For the incidence of POAF, sotalol, amiodarone, BBs, posterior pericardiotomy, atrial pacing, magnesium, polyunsaturated fatty acids, colchicine, glucocorticoid and statin had positive results compared to placebo with statistical significance. The best three therapeutics were sotalol (OR 0.29, 95% CI 0.21-0.41; probability of being best 84.6%), amiodarone (OR 0.39, 95% CI 0.31-0.48) and BBs (OR 0.39, 95% CI 0.31-0.49). For safety, BBs (OR 4.09, 95% CI 2.10-7.96), magnesium (OR 2.51, 95% CI 1.09-5.76) and sotalol (OR 2.07, 95% CI 1.06-4.05) were associated with higher incidence of hypotension. Sotalol (OR 2.80, 95% CI 1.66-4.74) and amiodarone (OR 2.27, 95% CI 1.66-3.10) were associated with higher incidence of bradycardia. For secondary outcomes, no significant effect on all-cause or cardiovascular mortality was observed. Amiodarone was the only intervention that reduced stroke rate (OR 0.57, 95% CI 0.34-0.96). Conclusions: Sotalol appeared to be superior in efficiency compared with others. BBs do not work as well as we expected with the highest incidence of hypotension.Further studies are required to define the better interventions

Abstract 14215: Mortality and Readmission Among Medicare Beneficiaries Hospitalized for Heart Failure Who Are Treatment Candidates for SGLT-2 Inhibitors

Background: SGLT2i form the latest pillar in the management of HFrEF and appear effective across a range of patient profiles. There is increasing interest around initiation of SGLT2i during hospitalization, yet little is known about the putative benefits of this implementation strategy. Methods: We evaluated Medicare beneficiaries with HFrEF (≤40%) hospitalized at 228 sites in the GWTG-HF Registry in 2016 who had linked claims data for ≥1 year post-discharge. We identified those eligible for a SGLT2i under the FDA label for dapagliflozin (excluding eGFR&lt;30 mL/min per 1.73 m 2 , dialysis, or type 1 diabetes). We evaluated 1-year outcomes overall and among key subgroups (age≥75y, sex, race, hospital region, eGFR, diabetes status, triple therapy). Results: Among 7,767 patients hospitalized for HFrEF, 6,218 (80%) would be SGLT2i candidates (mean age 79±8y, 38% women, 12% Black). Among eligible candidates, discharge use of β-blockers, ACEi/ARB, MRA, ARNI, and triple therapy (ACEi/ARB/ARNI+β-blocker+MRA) was in 86%, 65%, 30%, 3%, and 21%, respectively. Treatment candidates faced a 1-year incidence [95% CI] of mortality and HF readmission of 38% [36-39%] and 32% [31-33%], respectively, and each exceeded 25% across all key subgroups. Among 1,301 beneficiaries eligible for already on triple therapy, 1-year incidence of mortality was 26% [24-28%] and 1-year HF readmission was 30% [27-32%]. Conclusions: Medicare beneficiaries eligible for SGLT2i after HF hospitalization, including those well-treated with other disease-modifying therapies, face high risks of mortality and HF readmission by 1 year. Whether these heightened risks can be modified with implementation of SGLT2i at time of a worsening HF event is the subject of ongoing clinical trials.