Amiodarone and ß-blocker combination therapy versus ß-blocker monotherapy for ICD shock prevention: A meta-analysis.

While implantable cardioverter-defibrillator (ICD) shocks are a lifesaving therapy, they can negatively affect the patient's quality of life. Amiodarone is commonly combined with ß-blockers (BB) in ICD recipients. However, this combination therapy's efficacy in preventing shocks compared to standard BB monotherapy is not well studied. The aim of this systematic review and meta-analysis is to determine if combined amiodarone and BB therapy improves prevention of ICD shock delivery compared to BB monotherapy. We performed a comprehensive literature search using PubMed, Cochrane, and Web of Science databases, for studies that assess the impact of amiodarone and BB versus BB monotherapy in patients with an ICD. The primary outcome was a total number of ICD shocks delivered by the end of the study period. Four studies: three retrospective studies and one randomized controlled trial (RCT), with a total of 5818 patients with ICDs, were included in the analysis. Follow-up periods ranged from 1 to 5 years. The combined amiodarone and BB group was not associated with a significantly lower number of ICD shocks compared to the BB monotherapy group (OR, 0.76; 95% CI, 0.44-1.31; P = .32). A combination therapy of amiodarone and BB was not associated with any further reduction in ICD shocks, hospitalizations, or mortality. Additional RCTs are recommended to further validate our findings.

Treatment of long COVID complicated by postural orthostatic tachycardia syndrome-Case series research.

Background: Coronavirus disease 2019 (COVID-19) sequelae, also known as long COVID, can present with various symptoms. Among these symptoms, autonomic dysregulation, particularly postural orthostatic tachycardia syndrome (POTS), should be evaluated. However, previous studies on the treatment of POTS complicated by COVID-19 are lacking. Therefore, this study aimed to investigate the treatment course of long COVID complicated by POTS. Methods: The medical records of patients who complained of fatigue and met the criteria for POTS diagnosis were reviewed. We evaluated the treatment days, methods and changes in fatigue score, changes in heart rate on the Schellong test, and social situation at the first and last visits. Results: Thirty-two patients with long COVID complicated by POTS were followed up (16 males; median age: 28 years). The follow-up period was 159 days, and the interval between COVID-19 onset and initial hospital attendance was 97 days. Some patients responded to ß-blocker therapy. Many patients had psychiatric symptoms that required psychiatric intervention and selective serotonin reuptake inhibitor prescription. Changes in heart rate, performance status, and employment/education status improved from the first to the last visit. These outcomes were believed to be because of the effects of various treatment interventions and spontaneous improvements. Conclusions: Our study suggests that the condition of 94% of patients with POTS complicated by long COVID will improve within 159 days. Therefore, POTS evaluation should be considered when patients with long COVID complain of fatigue, and attention should be paid to psychological symptoms and the social context.

A case of reinitiation of modified electroconvulsive therapy 2 weeks after modified electroconvulsive therapy-induced Takotsubo cardiomyopathy in a male patient with major depressive disorder.

Background: Takotsubo cardiomyopathy (TCM) is a left ventricular dysfunction resembling acute coronary syndrome. Its prognosis is generally favorable; however, a subset of patients may present with severe complications. TCM is a rare side-effect of modified electroconvulsive therapy (ECT); it has been reported in 22 female and two male patients. Eight cases of ECT reinitiation after TCM have been reported (all females), with the shortest duration being 3 weeks. Case Presentation: We report the case of a 61-year-old man with a history of major depressive disorder and no history of heart disease or previous ECT treatment. Antidepressants had been ineffective, and ECT was indicated. After the third ECT session, the patient complained of chest pain and shortness of breath. Electrocardiography revealed ST elevation, and catheter angiography was used to diagnose TCM. The patient had mild heart failure but remained stable. Recognizing that ECT was effective, the patient asked for it to be reinitiated. We confirmed that the cardiac function had been normalized, applied a bisoprolol fumarate patch as a preventive measure, and reinitiated ECT 14 days after the onset of TCM. ECT was performed five times, with no recurrence of TCM and a marked improvement in depression. Conclusion: We describe a male patient with major depressive disorder who underwent reinitiation of ECT 2 weeks after ECT-induced TCM. Therefore, TCM should be recognized as a side-effect of ECT, even in men. Moreover, depending on whether the patient's condition is stable, ECT can be successfully performed in patients with TCM.

Successful treatment with ivabradine in a ß-blocker-refractory patient with acute decompensated heart failure with reduced ejection fraction.

Ivabradine is an established treatment for chronic heart failure with reduced ejection fraction (HFrEF); however, it is not used for acute heart failure treatment. Negative inotropic effects (NIE) often limit the up-titration of ß-blockers. Contrarily, ivabradine has no NIE, and enables ß-blockers usage for treating patients with acute decompensated HFrEF.

Impact of bisoprolol transdermal patch on early recurrence during the blanking period after atrial fibrillation ablation.

BACKGROUND: Early recurrences of atrial arrhythmias (ERAAs) after ablation may require therapeutic intervention. The optimal medical therapy that prevents ERAAs requires clarification. This study aimed to compare the incidence of ERAAs between patients who received or did not receive bisoprolol transdermal patches (BTPs) at 3 months postablation. METHODS: This single-center retrospective study enrolled 203 consecutive patients with paroxysmal atrial fibrillation (AF) who had undergone their first ablation, comprising 59 in the BTP group and 144 in the non-BTP group. Follow-up assessments were conducted monthly for 3 months. We evaluated the incidence of ERAAs. RESULTS: During the initial 1-week observational period, the rate of ERAAs was lower in the BTP group (5.0%) than that in the non-BTP group (18.8%) (P = .013). At 3 months postablation, the rate of ERAAs was lower in the BTP group (6.8%) than that in the non-BTP group (25.7%) (P = .002). The cumulative freedom from ERAAs was significantly lower in the BTP group than in the non-BTP group (log-rank: P = .003). Administering BTPs was an independent factor that protected against ERAAs (odds ratio 0.181, [95% confidence interval 0.059-0.559], P = .003). CONCLUSION: BTPs may prevent ERAAs after ablation.

Persistent wheezing caused by carvedilol overdose in a non-asthmatic man.

BACKGROUND: Cardiovascular dysfunction is the main manifestation of ß-blocker intoxication; however, respiratory manifestations have rarely been reported. CASE PRESENTATION: A 41-year-old man, who had ingested 300 mg carvedilol in a suicide attempt, was transferred to our emergency department. The patient had wheezing on arrival; however, he had no known history of bronchial asthma. In the absence of signs of heart failure, we gave the patient inhaled procaterol, a short-acting ß2 agonist. The wheezing disappeared approximately 60 h after carvedilol ingestion and did not recur thereafter. CONCLUSION: We report a case of wheezing caused by carvedilol intoxication. Although rare, clinicians should recognize that wheezing or bronchospasm can develop following ß-blocker intoxication, for which a short-acting ß2 agonist could be indicated.

ß-Blockers and 1-Year Postdischarge Mortality for Heart Failure and Reduced Ejection Fraction and Slow Discharge Heart Rate.

Background Many hospitalized patients with heart failure and reduced ejection fraction ( HF r EF ) have a slow heart rate at discharge, and the effect of ß-blockers may be reduced in those patients. We sought to examine the variable effect of ß-blockers on clinical outcomes according to the discharge heart rate of hospitalized HF r EF patients. Methods and Results The KorAHF (Korean Acute Heart Failure) registry consecutively enrolled 5625 patients hospitalized for acute heart failure. In this analysis, we included patients with HF r EF (left ventricular ejection fraction ≤40%). Slow heart rate was defined as <70 beats per minute regardless of the use of ß-blockers. The primary outcome was 1-year all-cause postdischarge death according to heart rate. Among 2932 patients with HF r EF , 840 (29%) had a slow heart rate and 56% received ß-blockers at discharge. Patients with slow heart rates were older and had lower 1-year mortality than those with high heart rates ( P<0.001). A significant interaction between discharge heart rate and ß-blocker use was observed ( P<0.001 for interaction). When stratified, only patients without a ß-blocker prescription and with a high heart rate showed higher 1-year mortality. In a Cox-proportional hazards regression analysis, ß-blocker prescription at discharge was associated with 24% reduced risk for 1-year mortality in patients with high heart rates (hazard ratio: 0.76; 95% CI, 0.61-0.95) but not in those with slow heart rates (hazard ratio: 1.02; 95% CI, 0.68-1.55). Conclusions Many patients with acute heart failure have slow discharge heart rates, and ß-blockers may have a limited effect on HF r EF and slow discharge heart rate. Clinical Trial Registration URL : http://www.clinicaltrial.gov . Unique identifier: NCT 01389843.

Genome-Wide Meta-Analysis of Blood Pressure Response to ß1-Blockers: Results From ICAPS (International Consortium of Antihypertensive Pharmacogenomics Studies).

BackgroundThere exists a wide interindividual variability in blood pressure (BP) response to ß1-blockers. To identify the genetic determinants of this variability, we performed a pharmacogenomic genome-wide meta-analysis of genetic variants influencing ß1-blocker BP response.Methods and ResultsGenome-wide association analysis for systolic BP and diastolic BP response to ß1-blockers from 5 randomized clinical trials consisting of 1254 patients with hypertension of European ancestry were combined in meta-analysis and single nucleotide polymorphisms (SNPs) with P<10-4 were tested for replication in 2 independent randomized clinical trials of ß1-blocker-treated patients of European ancestry (n=1552). Regions harboring the replicated SNPs were validated in a ß1-blocker-treated black cohort from 2 randomized clinical trials (n=315). A missense SNP rs28404156 in BST1 was associated with systolic BP response to ß1-blockers in the discovery meta-analysis (P=9.33×10-5, ß=-3.21 mm Hg) and replicated at Bonferroni significance (P=1.85×10-4, ß=-4.86 mm Hg) in the replication meta-analysis with combined meta-analysis approaching genome-wide significance (P=2.18×10-7). This SNP in BST1 is in linkage disequilibrium with several SNPs with putative regulatory functions in nearby genes, including CD38, FBXL5, and FGFBP1, all of which have been implicated in BP regulation. SNPs in this genetic region were also associated with BP response in the black cohort.ConclusionsData from randomized clinical trials of 8 European ancestry and 2 black cohorts support the assumption that BST1 containing locus on chromosome 4 is associated with ß1-blocker BP response. Given the previous associations of this region with BP, this is a strong candidate region for future functional studies and potential use in precision medicine approaches for BP management and risk prediction.

Efficacy and safety of cardioversion with continuous landiolol infusion for atrial tachyarrhythmia in an inflammatory state caused by volvulus in a child with TARP syndrome and postoperative tetralogy of Fallot.

A 2-year-old boy was diagnosed with TARP syndrome and underwent surgery for tetralogy of Fallot. He developed fever and had an acute abdomen. After 12 hours, atrial tachyarrhythmia (300 beats/min [bpm]) occurred. After nine administration of adenosine and two cardioversions, it relapsed promptly. Landiolol (10 µg/kg/min) was administered until the heart rate decreased to 270 bpm, and cardioversion was performed until sinus rhythm was normal. Exploratory laparotomy revealed small bowel volvulus. Systemic inflammation causing an acute abdomen may be associated with atrial tachyarrhythmia in postoperative tetralogy of Fallot. We speculated that landiolol lowered the defibrillation threshold of the atrium.

Effect of ß-Blockers Beyond 3 Years After Acute Myocardial Infarction.

BACKGROUND: The optimal duration of ß-blocker therapy in patients with acute myocardial infarction (AMI) is unknown. We aimed to evaluate the late effect of ß-blockers in patients with AMI. METHODS AND RESULTS: We enrolled all consecutive patients who presented with AMI at Seoul National University Bundang Hospital, between June 3, 2003 and February 24, 2015. The primary end point was 5-year all-cause mortality, depending on the use of ß-blockers at discharge, 1 year after AMI, and 3 years after AMI. Of 2592 patients, the prescription rates of ß-blockers were 72%, 69%, 63%, and 60% at discharge and 1, 3, and 5 years after AMI, respectively. The patients who were receiving ß-blocker therapy had more favorable clinical characteristics, such as younger age (62 versus 65 years; P<0.001). They received reperfusion therapy more often (92% versus 80%; P<0.001) than those without ß-blocker prescription. In the univariate analysis, the patients with ß-blocker prescription had lower 5-year mortality at all time points. In the Cox model after adjustment for significant covariates, ß-blocker prescription at discharge was associated with a 29% reduced mortality risk (hazard ratio, 0.71; 95% confidence interval, 0.55-0.90; P=0.006); however, ß-blocker prescriptions at 1 and 3 years after AMI were not associated with reduced mortality. CONCLUSIONS: The beneficial effect of ß-blocker therapy after AMI may be limited until 1 year after AMI. Whether late ß-blocker therapy beyond 1 year after AMI offers clinical benefits should be confirmed in further clinical trials.

Guideline-Directed Medical Therapy for Patients With Heart Failure With Midrange Ejection Fraction: A Patient-Pooled Analysis From the Kor HF and Kor AHF Registries.

Background Although current guidelines now define heart failure with midrange ejection fraction ( HF mr EF ) as HF with a left ventricular EF of 40% to 49%, there are limited data on response to guideline-directed medical therapy in patients with HF mr EF . The current study aimed to evaluate the association between ß-blocker, renin-angiotensin system blocker ( RASB ), or aldosterone antagonist ( AA ) treatment with clinical outcome in patients with HF mr EF . Methods and Results We performed a patient-level pooled analysis on 1144 patients with HF mr EF who were hospitalized for acute HF from the Kor HF (Korean Heart Failure) and Kor AHF (Korean Acute Heart Failure) registries. The study population was divided between use of ß-blocker, RASB , or AA to evaluate the guideline-directed medical therapy in patients with HF mr EF . Sensitivity analyses, including propensity score matching and inverse-probability-weighted methods, were performed. The use of ß-blocker in the discharge group showed significantly lower rates of all-cause mortality compared with those who did not use a ß-blocker (ß-blocker versus no ß-blocker, 30.7% versus 38.2%; hazard ratio, 0.758; 95% confidence interval, 0.615-0.934; P=0.009). Similarly, the RASB use in the discharge group was associated with the lower risk of mortality compared with no use of RASB ( RASB versus no RASB , 31.9% versus 38.1%; hazard ratio, 0.76; 95% confidence interval, 0.618-0.946; P=0.013). However, there was no significant difference in all-cause mortality between AA and no AA in the discharge group ( AA versus no AA , 34.2% versus 34.0%; hazard ratio, 1.063; 95% confidence interval, 0.858-1.317; P=0.578). Multiple sensitivity analyses showed similar trends. Conclusions For treatment of acute HFmrEF after hospitalization, ß-blocker and RASB therapies on discharge were associated with reduced risk of all-cause mortality. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01389843.

Antihypertensive Treatment With ß-Blockade in Patients With Asymptomatic Aortic Stenosis and Association With Cardiovascular Events.

BACKGROUND: Patients with aortic stenosis (AS) often have concomitant hypertension. Antihypertensive treatment with a ß-blocker (Bbl) is frequently avoided because of fear of depression of left ventricular function. However, it remains unclear whether antihypertensive treatment with a Bbl is associated with increased risk of cardiovascular events in patients with asymptomatic mild to moderate AS. METHODS AND RESULTS: We did a post hoc analysis of 1873 asymptomatic patients with mild to moderate AS and preserved left ventricular ejection fraction in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. Propensity-matched Cox regression and competing risk analyses were used to assess risk ratios for all-cause mortality, sudden cardiac death, and cardiovascular death. A total of 932 (50%) patients received Bbl at baseline. During a median follow-up of 4.3±0.9 years, 545 underwent aortic valve replacement, and 205 died; of those, 101 were cardiovascular deaths, including 40 sudden cardiovascular deaths. In adjusted analyses, Bbl use was associated with lower risk of all-cause mortality (hazard ratio 0.5, 95% confidence interval 0.3-0.7, P<0.001), cardiovascular death (hazard ratio 0.4, 95% confidence interval 0.2-0.7, P<0.001), and sudden cardiac death (hazard ratio 0.2, 95% confidence interval 0.1-0.6, P=0.004). This was confirmed in competing risk analyses (all P<0.004). No interaction was detected with AS severity (all P>0.1). CONCLUSIONS: In post hoc analyses Bbl therapy did not increase the risk of all-cause mortality, sudden cardiac death, or cardiovascular death in patients with asymptomatic mild to moderate AS. A prospective study may be warranted to determine if Bbl therapy is in fact beneficial. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.

Relationship Between ß-Blocker Therapy at Discharge and Clinical Outcomes in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The evidence supporting the use of ß-blockers in patients with acute coronary syndrome after successful percutaneous coronary intervention has been inconsistent and scarce. METHODS AND RESULTS: Between March 1, 2009, and December 30, 2014, a total of 3180 eligible patients with acute coronary syndrome undergoing percutaneous coronary intervention were consecutively enrolled. The primary end point was all-cause death and the secondary end point was a composite of all-cause death, nonfatal myocardial infarction, heart failure readmission, and cardiogenic hospitalization. Patients were compared according to the use of ß-blockers at discharge. Compared with the no ß-blocker group, the risk of all-cause death was significantly lower in the ß-blocker group (hazard ratio [HR], 0.33; 95% CI, 0.17-0.65 [P=0.001]). A consistent result was obtained in multiple adjusted model and propensity score-matched analysis. The use of ß-blockers was also associated with decreased risk of composite of adverse cardiovascular events (HR, 0.47; 95% CI, 0.28-0.81 [P=0.006]), although statistical significance disappeared after multivariable adjustment and propensity score matching. Furthermore, we performed post hoc analysis for the subsets of patients and the results revealed that patients with non-ST-segment elevation myocardial infarction benefited the most from ß-blocker therapy at discharge (HR, 0.04; 95% CI, 0.00-0.27 [P=0.001]), and the use of <50% of target dose was significantly associated with better outcome compared with no ß-blocker use, rather than ≥50% of target dose. CONCLUSIONS: The administration of relatively low ß-blocker dose is associated with improved clinical outcomes among patients with acute coronary syndrome after successful percutaneous coronary intervention, especially for patients with non-ST-segment elevation myocardial infarction.

Ventricular-Vascular Coupling in Marfan and Non-Marfan Aortopathies.

BACKGROUND: Marfan syndrome (MFS) and familial non-syndromal thoracic aortic aneurysm and dissection (ns-TAAD) are genetic aortopathies causing aortic dilatation with increased aortic stiffness. Left ventricular (LV) contractility and ventricular-vascular coupling index (VVI) were compared between MFS and ns-TAAD and determinants of VVI were investigated. METHODS AND RESULTS: Patients with MFS (M 57, F 47) and ns-TAAD (M 72, F 39) were studied by echocardiography and compared with controls (M 77, F 71). Aortic geometry, hemodynamics, LV work, LV contractility (end-systolic elastance [Ees]), and VVI were documented. Aortic sinuses were equally dilated in MFS (19.7±2.4) and ns-TAAD (19.8±1.8) compared to controls (16.2±1.4 mm·m-2, P<0.001). Aortic stiffness index was increased in MFS (9.7±5.1) and ns-TAAD (10.8±4.7) versus controls (5.4±2.0, P<0.01); LV stroke work was unchanged in MFS (436±74) compared to controls (435±60) but increased in ns-TAAD (492±109 mJ·m-2 P<0.01). The LV Ees was reduced in MFS (1.32±0.19) compared to controls (1.65±0.29 mm Hg·mL-1, P<0.01) but increased in ns-TAAD (1.83±0.30, P<0.01) and VVI was abnormal in MFS (0.71±0.11) compared to controls (0.62±0.07, P<0.01) and ns-TAAD (0.62±0.09). Treatment with ß-blockers was associated with partial normalization of VVI in MFS. A VVI ≥0.8 was associated with increased risk of death and heart failure in MFS. CONCLUSIONS: Left ventricular contractility and ventricular-vascular coupling are abnormal in MFS but preserved in ns-TAAD, and are independent of aortic stiffness, consistent with intrinsic impairment of myocardial contractility in MFS.

Prognostic Benefits of Carvedilol, Bisoprolol, and Metoprolol Controlled Release/Extended Release in Hemodialysis Patients with Heart Failure: A 10-Year Cohort.

BACKGROUND: Heart failure is a highly prevalent cardiovascular complication among patients receiving long-term hemodialysis, but the benefits of carvedilol, bisoprolol, and metoprolol controlled release/extended release on the outcomes of these patients remain unclear. In this study, we address the use of these 3 ß-blockers and their associations with mortality. METHODS AND RESULTS: Long-term hemodialysis patients, aged ≥35 years, with new-onset heart failure and receiving various medications were identified through the use of 1999-2010 data from the Taiwan National Health Insurance Research Database. From the total of 4435 heart failure patients, we selected 1700 new users of the 3 ß-blockers (study group) and 1700 nonusers (control group), by using matched cohorts according to their propensity scores, and then compared the 5-year all-cause mortality rates by using Cox proportional hazard regressions and time-dependent covariate adjustment. During 3944 person-years of follow-up, 666 (39.2%) deaths occurred within the study group, compared with 918 (54%) deaths during 2893 person-years of follow-up in the control group. The 5-year mortality rate for the study (control) group was 54.5% (70.3%); P<0.001. Adjusted hazard regression analyses revealed that the therapeutic effects of ß-blockers remained significant for all-cause mortality (hazard ratio 0.80, 95% CI 0.72 to 0.90). Subgroup analyses revealed that patients in the study group receiving ß-blockers plus renin-angiotensin system antagonists exhibited the lowest mortality rate, while the highest mortality rate was found among patients in the control group receiving neither ß-blockers nor renin-angiotensin system antagonists. CONCLUSIONS: This study demonstrates that the 3 ß-blockers were associated with improved survival in long-term hemodialysis patients with heart failure.