Atrioventricular Nodal Blocker Research Articles

BRASH syndrome with a complete heart block- a case report

IntroductionBRASH syndrome (Bradycardia, Renal failure, Atrioventricular (AV) nodal blocking agent, Shock and Hyperkalemia) is a recently emerging diagnosis that describes the profound bradycardia seen in patients on AV nodal blockers who present with acute kidney injury (AKI) and hyperkalemia.Case presentationWe present a case of a 68 years old female patient with past history of hypertension taking atenolol and Enalapril presented to emergency department with the complaint of loss of consciousness of 02 hours duration. She had 03 days history of fatigue, poor oral intake, decreased urine output, appetite loss, vertigo and global headache. Her vital signs were blood pressure of 60/40 mmHg, absent radial pulse and temperature of 36.4 °C. Her systemic examination was remarkable for dry buccal mucosa; apical heart rate was 22 beats per minute. Glasgow Coma Scale was 13/15. Her laboratory tests showed creatinine of 1.83 mg/dL, blood urea nitrogen of 89 mg/dL and potassium elevated to the level of 6.39 mEq/dL. ECG revealed complete heart block with a normal QT interval and T waves and no U waves with ventricular rate of 22 beats per minute. Her previous medications were discontinued and the patient was resuscitated with intravenous (IV) fluids. She was given 03 doses of 1 mg atropine every 5 minutes but there was no increment in heart rate. She was given 50% dextrose with 10 international units of regular insulin, 1 g of calcium gluconate and Intravenous perfusion of norepinephrine and dopamine. Subsequently, after 14 hours of ICU admission the patient had a cardiac arrest with asystole and resuscitation was attempted but she couldn’t survive.ConclusionBRASH syndrome is largely an under-recognized life threatening clinical diagnosis. Physicians should have high index of suspicion for BRASH when they encounter patients with bradycardia, hyperkalemia, and renal failure, as timely diagnosis is crucial in the management.

A case of unstable bradycardia requiring comprehensive management in the emergency department: BRASH syndrome

Bradycardia, renal failure, Atrioventricular (AV) nodal Blocker Drug Use, Shock, and Hyperkalemia (BRASH) syndrome is a clinical condition frequently seen in emergency services but with low diagnostic awareness. In cases of the syndrome, its cause was determined to be the synergistic effect of hyperkalemia due to renal failure and the use of AV nodal blocker drugs. The common features of patients diagnosed with BRASH syndrome are moderately elevated potassium levels and symptomatic bradycardia with various ECG findings (such as junctional bradycardia, atrioventricular block, and sinus bradycardia). Detection of these findings is very important in the diagnosis process. In this case report, we aimed to reveal the important points in the diagnosis of BRASH syndrome, ECG findings, and treatment approach.

Bilateral Pulmonary Embolism Masked by New-Onset Atrial Fibrillation with Rapid Ventricular Rate: The Role of Mechanical Thrombectomy

Patient: Male, 70-year-old Final Diagnosis: Atrial fibrillation • pulmonary embolism Symptoms: Dyspnea Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Unusual clinical course Background:Management of atrial fibrillation (AF) with rapid ventricular rate in the setting of submassive pulmonary emboli (PE) has not been well defined in the literature. It is challenging as the hemodynamics caused by a PE can change the management of AF. We report a case of bilateral PE masked by new-onset AF with rapid ventricular rate that was treated pharmaceutically and mechanically, with thrombectomy.Case Report:An 85-year-old man presented with gradual dyspnea and was found to be in AF with rapid ventricular rate (~160–180 bpm). The patient had tachypnea and hypoxia requiring oxygen administration. On physical examination, he had euvolemia. Chest X-ray did not reveal pulmonary vascular congestion. He was started on standard AF management with atrioventricular nodal blockers. Laboratory tests revealed a normal troponin level but mildly elevated B-type natriuretic peptide and lactate. Because his dyspnea was out of proportion to the physical examination, radiographic, and laboratory findings, a D-dimer level was obtained and was elevated. Computed tomography with pulmonary angiogram showed extensive bilateral PE. An echocardiogram (TTE) showed evidence of right ventricular failure. The patient underwent mechanical thrombectomy with clot retrieval, deterring the risk of hemodynamic collapse that would have ensued with atrioventricular nodal blockers monotherapy. On repeat TTE, right ventricular dysfunction was completely resolved and the remaining hospitalization was uneventful.Conclusions:In patients with concomitant AF with rapid ventricular rate and submassive PE, the use of mechanical thrombectomy, in addition to the standard AF management, could be beneficial in deterring the risk of hemodynamic collapse.

Trends in Calcium Channel Blocker Use in Patients with Heart Failure with Reduced Ejection Fraction and Comorbid Atrial Fibrillation

BackgroundHeart failure with reduced ejection fraction and atrial fibrillation commonly coexist. Most calcium channel blockers are not recommended in heart failure with reduced ejection fraction, but their use has been seldom evaluated. For patients with heart failure with reduced ejection fraction and comorbid atrial fibrillation, we sought to 1) determine the proportion discharged on contraindicated calcium channel blockers, 2) describe how clinicians’ use of these medications at discharge have changed over time, and 3) identify predictors for contraindicated calcium channel blocker prescription at discharge. MethodsWe analyzed 395 patients discharged with heart failure with reduced ejection fraction and atrial fibrillation between 2008 and 2018. Discharge on a contraindicated calcium channel blocker (any calcium channel blocker except amlodipine) was the primary outcome. Changes in calcium channel blocker prescription over time were evaluated with a Cochran-Armitage trend test. Multivariable logistic regression was used to identify predictors of calcium channel blocker prescription at discharge. ResultsTwenty-nine (7.3%) patients were discharged on a contraindicated calcium channel blocker without change over time (Ptrend = .38). Of these, 26 (86.7%) were discharged on multiple atrioventricular nodal blocking medications. Hypertension (odds ratio [OR] 7.87; 95% confidence interval [CI], 1.04-59.40) and female sex (OR 3.01; 95% CI, 1.36-6.67) were both associated with contraindicated calcium channel blocker prescription at discharge while diabetes mellitus was negatively associated with this outcome (OR 0.34; 95% CI, 0.14-0.88). ConclusionOne in 14 patients with heart failure with reduced ejection fraction and comorbid atrial fibrillation were discharged on a contraindicated calcium channel blocker, without change over time. Most patients were discharged on multiple atrioventricular nodal blockers, highlighting potential need for greater coordination between discharging physicians, pharmacists, and electrophysiology.

BRASH syndrome: more than just syncope

The pentad of bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia describes the BRASH syndrome, a newly recognized phenomenon in which accumulation of potassium and renally excreted atrioventricular nodal blockers cause a cycle of bradycardia, hypoperfusion, and worsening renal function. Here, we describe a case of BRASH in an elderly woman whose medications had recently changed, and who presented with bradycardia, anuria, and hypotension. Resolution of symptoms occurred over hours after the right treatment was started. Furthermore, we review case reports written in recent years for common BRASH syndrome patient characteristics.

Effectiveness of a simple medication adjustment protocol for optimizing peri-cardioversion rate control: A derivation and validation cohort study.

BackgroundRate control medications are foundational in the management of persistent atrial fibrillation (AF). There are no guidelines for adjusting these medications prior to elective direct-current cardioversion (DCCV).ObjectiveTo derive and validate a preprocedural medication adjustment protocol that maintains peri-DCCV rate control and minimizes risk of postconversion bradycardia, pauses, need for pacing, and cardiopulmonary resuscitation (CPR).MethodsConsecutive patients with persistent AF awaiting elective DCCV across 2 hospitals were screened for inclusion into derivation, validation, and control cohorts. In the derivation cohort, each patient taking an atrioventricular (AV) nodal blocker had medications adjusted based on heart rate (HR) 2 days before DCCV, and the magnitude of dose adjustment was compared with peri-DCCV HR. The adjustment protocol that achieved the highest percentage of optimal peri-DCCV rate control was tested prospectively in the validation cohort and compared to a standard-of-care control group.ResultsThe optimal protocol from the derivation cohort (n = 71), based on the 2-day pre-DCCV HR, was to (1) CONTINUE AV nodal blocker for HR ≥ 100 beats per minute (bpm), (2) reduce dose by ONE increment when 80–99 bpm, (3) reduce dose by TWO increments when 60–79 bpm, and (4) HOLD when <60 bpm. In the prospective validation cohort (n = 106), this protocol improved peri-DCCV rate control (82% vs 62%, P < .001) compared to current standard of care (n = 107). There were no conversion pauses ≥5 seconds, need for pacing, or CPR post-DCCV.ConclusionThis simple preprocedural medication adjustment protocol provides an effective strategy of optimizing peri-DCCV rate control in patients with AF.

Too slow and too high

A 77-year-old woman on metoprolol and lisinopril presented to an emergency department with giddiness after vomiting for few hours. She was found to have low blood pressure and bradycardia 38 beats per minute due to atrioventricular nodal blockade. Her bradycardia was refractory to atropine and dopamine infusion; but improved with calcium gluconate. She was found to have acute kidney injury and hyperkalemia at 6.4 mEq/L. This is a case of Bradycardia, Renal Failure, Atrioventricular-Nodal Blockers, Shock, and Hyperkalemia (BRASH) syndrome, precipitated by dehydration and perpetuated by atrioventricular blockade, illustrating the degree of bradycardia and electrocardiographic changes being out of proportion to the potassium level. BRASH syndrome should be recognized and intervened early in the course to avoid the patient entering a vicious cycle that could be rapidly fatal.

BRASH syndrome: an emerging emergency

BRASH syndrome (bradycardia, renal failure, atrioventricular nodal blockers, shock and hyperkalemia) is an emerging and distinct condition that occurs due to the synergistic effects of hyperkalaemia and AVN blockers on the heart. Only a few case reports have been described in the medical literature since 2016. We present an 88-year-old woman, known with hypertension, stage 5 chronic kidney disease (not on dialysis) and paroxysmal atrial fibrillation that presented with a history of four syncopal episodes in the past 2-months and had symptoms of heart failure for 1-day. Clinical examination revealed a blood pressure of 105/60 mmHg and a regular pulse rate of 31 beats per minute. Laboratory potassium concentration was 6.7 mmol/L and creatinine was 318 ¼mol/L. An electrocardiogram revealed a sinus bradycardia without features suggestive of hyperkalaemia. A diagnosis of BRASH syndrome was made. The patient received treatment addressing multiple factors involved in the pathogenesis of the syndrome and responded favourably. She was discharged 1-week later. In patients with syncope, BRASH syndrome should be considered when bradycardia is associated with hyperkalaemia, along with a history of AVN blocker use. It is important to recognise so that appropriate therapy can be instituted that addresses all the elements of the syndrome, rather than focusing on a single component.

Effect of Beta-blockers on Tachycardia in Patients with Pulmonary Embolism.

HypothesisBeta-blockers (BBs) lower the heart rate, which may mask the diagnosis of pulmonary embolism (PE) since one of the main clinical diagnoses of PE is tachycardia. The endpoint of our retrospective study is to determine if the pre-existing use of (BB) significantly affects the utility of these scoring criteria in diagnosing PE.IntroductionDiagnosing PE is a challenge because of the non-specificity of its symptoms and signs. The initial step is to assess the patient’s likelihood of having a PE. This involves using a scoring system to stratify patients into different levels of risk of having PE (for example, as ‘low,’ ‘moderate,’ or ‘high’ risk). Some of the commonly used criteria are Wells’ Score, Geneva Score, and Pulmonary Embolism Rule-out Criteria (PERC) Rule (Charlotte Rule).MethodologyThis retrospective study was conducted at St. Francis Medical Center. Subjects were taken from a patient population with a new diagnosis of PE (between 2010 and 2017) on the basis of computed tomography angiography (CTA) of the chest. Patients with sepsis or septic shock, heart block, atrioventricular (AV) nodal ablation, pacemaker placement, or taking more than one AV nodal blocker were excluded from the study. Subjects were categorized on the basis of beta-blocker consumption.ResultOut of a total of 170 cases, 71 patients were taking beta-blockers and 99 patients were not taking beta-blockers. Among the participants taking BBs, 30.4% had a heart rate <60 and 55.8% had a heart rate between 60 and 100.ConclusionBBs significantly obviate tachycardia in patients with PE. It falsely decreases the Wells’ Score and the Geneva Score and results in the inappropriate fulfilling of PERC criteria.

Ideal cardiovascular health and resting heart rate in the Multi-Ethnic Study of Atherosclerosis

Elevated resting heart rate (RHR) is associated with an increased cardiovascular disease (CVD) risk, but little is known about its association with cardiovascular health (CVH), assessed by the Life's Simple 7 (LS7) metrics. We explored whether ideal CVH was associated with RHR in a cohort free from clinical CVD. We conducted a cross-sectional analysis of baseline data (2000−2002) of 6457 Multi-Ethnic Study of Atherosclerosis participants in 2018. Each LS7 metric (smoking, physical activity, diet, body mass index, blood pressure, cholesterol and glucose) was scored 0–2. Total score ranged from 0 to 14. Scores of 0–8 indicate inadequate, 9–10 average, and 11–14 optimal CVH. RHR was categorized as <60, 60–69, 70–79 and ≥80 bpm. We used multinomial logistic regression to determine associations between CVH score and RHR, adjusting for age, sex, race/ethnicity, education, income, health insurance, and atrioventricular nodal blockers. Mean age of participants (standard deviation) was 62 (10) years; 53% were women; 47% had inadequate CVH, 33% average, and 20% optimal. Favorable CVH was associated with lower odds of having higher RHR. Compared to RHR <60 bpm, participants with optimal CVH had adjusted odds ratio (95% CI) of 0.55 (0.46–0.64) for RHR of 60-69 bpm, 0.34 (0.28–0.43) for 70–79 bpm, and 0.14 (0.09–0.22) for ≥80 bpm. A similar pattern was observed in the stratified analysis by sex, race/ethnicity and age. Favorable CVH was less likely to be associated with elevated RHR irrespective of sex, race/ethnicity and age. More research is needed to explore the usefulness of promoting ideal CVH to reduce elevated RHR, a known risk factor for CVD.

Low-dose Magnesium Sulfate Versus High Dose in the Early Management of Rapid Atrial Fibrillation: Randomized Controlled Double-blind Study (LOMAGHI Study).

We aim to determine the benefit of two different doses magnesium sulfate (MgSO4 ) compared to placebo in rate control of rapid atrial fibrillation (AF) managed in the emergency department (ED). We undertook a randomized, controlled, double-blind clinical trial in three university hospital EDs between August 2009 and December 2014. Patients>18 years with rapid AF (>120 beats/min) were enrolled and randomized to 9g of intravenous MgSO4 (high-dose group, n=153), 4.5 g of intravenous MgSO4 (low-dose group, n=148), or serum saline infusion (placebo group, n=149), given in addition to atrioventricular (AV) nodal blocking agents. The primary outcome was the reduction of baseline ventricular rate (VR) to 90 beats/min or less or reduction of VR by 20% or greater from baseline (therapeutic response). Secondary outcome included resolution time (defined as the elapsed time from start of treatment to therapeutic response), sinus rhythm conversion rate, and adverse events within the first 24 hours. At 4 hours, therapeutic response rate was higher in low- and high-MgSO4 groups compared to placebo group; the absolute differences were, respectively, 20.5% (risk ratio [RR]= 2.31, 95% confidence interval [CI]= 1.45-3.69) and +15.8% (RR= 1.89, 95% CI= 1.20-2.99). At 24 hours, compared to placebo group, therapeutic response difference was +14.1% (RR= 9.74, 95% CI= 2.87-17.05) with low-dose MgSO4 and +10.3% (RR= 3.22, 95% CI= 1.45-7.17) with high-dose MgSO4 . The lowest resolution time was observed in the low-dose MgSO4 group (5.2±2 hours) compared to 6.1±1.9 hours in the high-dose MgSO4 group and 8.4±2.5 hours in the placebo group. Rhythm control rate at 24 hours was significantly higher in the low-dose MgSO4 group (22.9%) compared to the high-dose MgSO4 group (13.0%, p=0.03) and the placebo group (10.7%). Adverse effects were minor and significantly more frequent with high-dose MgSO4 . Intravenous MgSO4 appears to have a synergistic effect when combined with other AV nodal blockers resulting in improved rate control. Similar efficacy was observed with 4.5 and 9 g of MgSO4 but a dose of 9g was associated with more side effects.

Resting heart rate and the incidence and progression of valvular calcium: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background and aimsLeft-sided valvular calcification is associated with cardiovascular disease (CVD) morbidity and mortality. Resting heart rate (RHR) may influence valvular calcium progression through shear stress. Whether RHR, an established CVD risk factor, is associated with valvular calcium progression is unknown. We assessed whether RHR predicts incidence and progression of mitral annular calcium (MAC) and aortic valve calcium (AVC) in a community-based cohort free of CVD at baseline. MethodsRHR was obtained from baseline electrocardiograms of 5498 MESA participants. MAC and AVC were quantified using Agatston scoring from cardiac computed tomography scans obtained at baseline and at a second examination during follow-up. We examined associations of RHR with incident MAC/AVC and annual change in MAC/AVC scores, after adjusting for demographics, CVD risk factors, physical activity, and atrioventricular nodal blocker use. ResultsAt baseline, participants had mean age of 62 ± 10 years and mean RHR of 63 ± 10 bpm; 12.3% and 8.9% had prevalent AVC and MAC, respectively. Over a median of 2.3 years, 4.1% and 4.5% developed incident AVC and MAC, respectively. Each 10 bpm higher RHR was significantly associated with incident MAC [Risk Ratio 1.17 (95% CI 1.03–1.34)], but not incident AVC. However, RHR was associated with AVC progression [β = 1.62 (0.45–2.80) Agatston units/year for every 10 bpm increment], but not MAC progression. ConclusionsHigher RHR was associated with MAC incidence and AVC progression, independent of traditional CVD risk factors. Future studies are needed to determine whether modification of RHR through lifestyle or pharmacologic interventions can reduce valvular calcium incidence or progression.

Abstract P367: Association Between Resting Heart Rate and Progression of Valvular Calcification

Background: Mitral annular calcification (MAC) and aortic valvular calcification (AVC) are progressive and linked to increased cardiovascular disease (CVD) morbidity and mortality. Few known modifiable risk factors associated with the progression of MAC and AVC exist. Resting heart rate (RHR) is an established independent risk factor for CVD. Due to the potential hemodynamic effects of RHR on development or progression of valve calcification, we assessed whether RHR is associated with the incidence and progression of MAC and AVC in a community-based cohort free of CVD and atrial fibrillation at baseline. Methods: We obtained RHR from baseline 12-lead electrocardiograms of 5,498 MESA cohort participants. We studied RHR as a continuous variable (per 1 SD increment) and also categorized at clinical cut points of &lt; 60, 60 - 69, 70 - 79, and ≥ 80 bpm. MAC and AVC were quantified (using Agatston scoring) from cardiac computed tomography scans obtained at baseline and at follow-up examinations 2 or 3. We examined associations between RHR and incident MAC/AVC and annual change in MAC/AVC scores, after adjusting for demographics, CVD risk factors, physical activity, and atrioventricular nodal blocker medication use. We used progressively adjusted parametric survival models for incident MAC/AVC and linear regression models for annual change in MAC/AVC. Results: At baseline, participants had a mean age of 62±10 years and mean RHR of 63±10 bpm; 12.3% and 8.9% had prevalent AVC and MAC [Agatston Units (AU) &gt;0], respectively. Over a median follow up time of 2.3 years, 4.1% and 4.5% developed incident AVC and MAC, respectively. Each 10 bpm higher RHR was significantly associated with incident MAC [Hazard Ratio 1.18 (95% CI 1.03-1.36)], but not incident AVC. However, RHR (per 10 bpm) was associated with AVC progression [β coeff 1.62 (0.45-2.80) AU/year], but not MAC progression. The association of RHR on annual change in AVC was modified by age and sex (p-interactions 0.006 and &lt;0.02, respectively) but not race/ethnicity. Each 10 bpm higher RHR was significantly associated with AVC progression for age &gt; 62 years [β coeff 2.94 (0.55, 5.34) AU/year] and male sex [3.49 (1.31, 5.67) AU/year]. The association between RHR and AVC progression was not significant for age ≤ 62 or female sex. Similar trends were seen using clinical cut-points for RHR. Conclusion: Higher RHR predicted incident MAC and AVC progression independent of traditional CVD risk factors. Future studies are needed to determine whether this association is causal and whether modification of RHR through lifestyle or pharmacologic interventions can reduce valvular calcium progression.

Clinical effectiveness of a systematic “pill-in-the-pocket” approach for the management of paroxysmal atrial fibrillation

For patients with symptomatic, sustained atrial fibrillation (AF), a "pill-in-the-pocket" antiarrhythmic drug (PIP-AAD) strategy has been proposed to reduce emergency department (ED) use. To assess the clinical utility of a protocolled PIP-AAD approach within contemporary practice. Consecutive patients who hemodynamically tolerated symptomatic, sustained AF were prospectively managed with the PIP-AAD strategy. All patients were given an atrioventricular nodal blocker 30 minutes prior to a single oral dose of a class Ic antiarrhythmic drug. If the initial PIP-AAD in the ED was efficacious and tolerated, PIP-AADs were given out of hospital for subsequent sustained AF episodes. Usage and complications were systematically recorded. During a median follow-up period of 565 days, 43 of 80 patients presented to the ED for initial PIP-AAD. Sinus rhythm was restored without complication in 30 of 43 patients. The reasons for initial PIP-AAD failure were inefficacy (6 patients), significant hypotension (4 patients), conversion to flutter necessitating cardioversion (2 patients), and syncopal conversion pause (1 patient). For the 30 patients with successful initial PIP-AAD, 159 out-of-hospital PIP-AAD treatments occurred (mean 5.3 ± SD 1.3 per patient). Compared with ED visits in the period prior to PIP-AAD initiation, there was a significant reduction in visits (2.6 ± 3.0 vs. 0.4±0.9 ED visits per patient, P < .001) and the need for cardioversion (2.3 ± 3.1 vs. 0.0 ± 0.2 treatments per patient, P< .001). Adverse events associated with out-of-hospital PIP-AAD include presyncope (3 of 30 patients), syncope necessitating pacemaker implantation (1 patient), and conversion to flutter (1patient). Out-of-hospital PIP-AAD can be an effective for highly selected patients; however, the rates of treatment failure and adverse events are clinically relevant, which limits the widespread application of a PIP-AAD approach.

Correlation of Iatrogenic Mild Hyperkalaemia and Bradyarrhythmia: A Problem of Polypharmacy in Elderly

Mild hyperkalaemia does not typically cause cardiac symptoms. However, for an elderly patient on atrio-ventricular (AV) nodal blocker, even mild hyperkalaemia may result in disastrous outcome. We report a case of persistent bradyarrythmia caused by iatrogenic hyperkalaemia in a patient who had concomitant use of AV nodal medication. An 81-year-old lady with multiple comorbidities and a long list of medications presented with symptomatic bradyarrhythmia. She, in fact, had two AV nodal blockers in her prescription, a beta-blocker and amiodarone. Her potassium level was found to be mildly elevated due to acute renal failure. She remained bradycardic despite initial treatment and was subsequently dependant on intravenous isoproterenol until her renal function improved. This case highlights the different threshold for manifestation of hyperkalaemic symptoms in a growing group of patients: elderly patients with multiple comorbidities and polypharmacy.

A Genome-Wide Association Study to Identify Genomic Modulators of Rate Control Therapy in Patients With Atrial Fibrillation

For many patients with atrial fibrillation, ventricular rate control with atrioventricular (AV) nodal blockers is considered first-line therapy, although response to treatment is highly variable. Using an extreme phenotype of failure of rate control necessitating AV nodal ablation and pacemaker implantation, we conducted a genome-wide association study (GWAS) to identify genomic modulators of rate control therapy. Cases included 95 patients who failed rate control therapy. Controls (n= 190) achieved adequate rate control therapy with ≤2 AV nodal blockers using a conventional clinical definition. Genotyping was performed on the Illumina 610-Quad platform, and results were imputed to the 1000 Genomes reference haplotypes. A total of 554,041 single-nucleotide polymorphisms (SNPs) met criteria for minor allele frequency (>0.01), call rate (>95%), and quality control, and 6,055,224 SNPs were available after imputation. No SNP reached the canonical threshold for significance for GWAS of p <5× 10(-8). Sixty-three SNPs with p <10(-5) at 6 genomic loci were genotyped in a validation cohort of 130 cases and 157 controls. These included 6q24.3 (near SAMD5/SASH1, p= 9.36× 10(-8)), 4q12 (IGFBP7, p= 1.75× 10(-7)), 6q22.33 (C6orf174, p= 4.86× 10(-7)), 3p21.31 (CDCP1, p= 1.18× 10(-6)), 12p12.1 (SOX5, p= 1.62× 10(-6)), and 7p11 (LANCL2, p= 6.51× 10(-6)). However, none of these were significant in the replication cohort or in a meta-analysis of both cohorts. In conclusion, we identified several potentially important genomic modulators of rate control therapy in atrial fibrillation, particularly SOX5, which was previously associated with heart rate at rest and PR interval. However, these failed to reach genome-wide significance.

Association of resting heart rate with carotid and aortic arterial stiffness: multi-ethnic study of atherosclerosis.

Resting heart rate is an easily measured, noninvasive vital sign that is associated with cardiovascular disease events. The pathophysiology of this association is not known. We investigated the relationship between resting heart rate and stiffness of the carotid (a peripheral artery) and the aorta (a central artery) in an asymptomatic multi-ethnic population. Resting heart rate was recorded at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA). Distensibility was used as a measure of arterial elasticity, with a lower distensibility indicating an increase in arterial stiffness. Carotid distensibility was measured in 6484 participants (98% of participants) using B-mode ultrasound, and aortic distensibility was measured in 3512 participants (53% of participants) using cardiac MRI. Heart rate was divided into quintiles and we used progressively adjusted models that included terms for physical activity and atrioventricular nodal blocking agents. Mean resting heart rate of participants (mean age, 62 years; 47% men) was 63 bpm (SD, 9.6 bpm). In unadjusted and fully adjusted models, carotid distensibility and aortic distensibility decreased monotonically with increasing resting heart rate (P for trend <0.001 and 0.009, respectively). The relationship was stronger for carotid versus aortic distensibility. Similar results were seen using the resting heart rate taken at the time of MRI scanning. Our results suggest that a higher resting heart rate is associated with an increased arterial stiffness independent of atrioventricular nodal blocker use and physical activity level, with a stronger association for a peripheral (carotid) compared with a central (aorta) artery.

Risk Factors for Bradycardia Requiring Pacemaker Implantation in Patients With Atrial Fibrillation

Symptomatic bradycardia may complicate atrial fibrillation (AF) and necessitate a permanent pacemaker. Identifying patients at increased risk for symptomatic bradycardia may reduce associated morbidities and health care costs. The aim of this study was to investigate predictors for developing bradycardia requiring a permanent pacemaker in patients with AF. The records of all patients treated for AF or atrial flutter in an academic hospital's emergency department from August 1, 2005, to July 31, 2008, were reviewed. Survival and the presence of a pacemaker as of November 1, 2011, were determined. Cases were defined as patients with pacemakers placed for bradycardia after their AF diagnoses. Patients without pacemakers who were followed constituted the control group. Variables for the logistic regression analysis were identified a priori. A post hoc model was fit adjusting for AF type and atrioventricular nodal blocker use. Of the 362 patients in the cohort, 119 cases had permanent pacemakers implanted for bradycardia after AF diagnosis, and 243 controls were alive without pacemakers. The median follow-up time was 4.5 years (interquartile range 3.8 to 5.4). Odds ratios were determined for age at the time of AF diagnosis (1.02, 95% confidence interval [CI] 1 to 1.04), female gender (1.58, 95% CI 0.95 to 2.63), previous heart failure (2.72, 95% CI 1.47 to 5.01), and African American race (0.33, 95% CI 0.12 to 0.94). The post hoc model identified permanent AF (odds ratio 2.99, 95% CI 1.61 to 5.57) and atrioventricular nodal blocker use (odds ratio 1.43, 95% CI 0.85 to 2.4). In conclusion, in patients with AF, heart failure and permanent AF each nearly triple the odds of developing bradycardia requiring a permanent pacemaker; although not statistically significant, our results suggest that women are more likely and African Americans less likely to develop bradycardia requiring pacemaker implantation.

Abstract P208: Functional Status, Rehospitalization, and Mortality Outcomes Among Acute Myocardial Infarction Patients with Prior and New-Onset Atrial Fibrillation

Background: Little data are available regarding differences in prognosis and health status between new-onset and prior atrial fibrillation (AF) among patients with acute myocardial infarction (AMI). Methods: The TRIUMPH study enrolled 4340 AMI patients who received longitudinal follow-up including SF-12 health status assessments through 1 year post-AMI. We compared 1-year mortality, rehospitalization, and functional status according to AF type (none, prior, new) after adjusting for differences in baseline characteristics. Results: A total of 212 AMI patients (4.9%) had prior AF and 254 (5.9%) had new-onset AF. Compared with no AF, new AF was associated with older age, male sex, first MI, worse baseline physical function, home atrioventricular nodal blocker use, and worse ventricular function (c-index 0.77). Rates of 1-year mortality were 6.2%, 14.5%, and 13.0%, and 1-year rehospitalization rates were 29.1%, 44.2%, and 36.8% for no, prior, and new AF, respectively. After multivariable adjustment, neither prior nor new AF was associated with increased 1-year mortality, and only prior AF was associated with increased risk of 1-year rehospitalization (Figure). After adjusting for baseline SF-12 physical function scores, patients with prior AF had lower 1-year scores than those with no AF (40.6 vs. 43.7, p &lt;0.003), whereas patients with new AF had similar scores (42.9 vs. 43.7, p=0.36). Conclusion: New-onset AF during AMI is associated with a number of comorbidities but, unlike prior AF, is not associated with adverse outcomes. These results raise the question of whether AF is itself a cause of or simply a marker of comorbidities leading to downstream adverse outcomes after AMI.

Antiarrhythmics After Ablation of Atrial Fibrillation (5A Study)

Background— We previously demonstrated that treatment with antiarrhythmic drugs (AADs) during the first 6 weeks after atrial fibrillation (AF) ablation reduces the incidence of clinically significant atrial arrhythmias and need for cardioversion or hospitalization for arrhythmia management. Whether early rhythm suppression decreases longer-term arrhythmia recurrence is unknown. We now report the 6-month follow-up data from this study. Methods and Results— The Antiarrhythmics After Ablation of Atrial Fibrillation study prospectively randomized patients with paroxysmal AF undergoing ablation to either receive (AAD group) or not receive (no-AAD group) AAD treatment for the first 6 weeks after ablation; all patients received atrioventricular nodal blockers. Physicians were encouraged to stop the AADs after the 6-week treatment period. All patients underwent 4 weeks of transtelephonic monitoring to document asymptomatic AF and an evaluation at 6 weeks and 6 months. A total of 110 patients (71% men) aged 55±9 years were randomized, with 53 to AAD and 57 to no AAD. At 6 months, there was no difference in freedom from AF between the early AAD and no-AAD groups (38/53 [72%] versus 39/57 [68%]; P =0.84). Lack of early AF recurrence during the initial 6-week period was the only independent predictor of 6-month freedom from AF (64/76 [84%] without early recurrence versus 13/34 [38%] with early recurrence; P =0.0001). Conclusions— Although short-term use of AADs after AF ablation decreases early recurrence of atrial arrhythmias, early use of AADs does not prevent arrhythmia recurrence at 6 months. Early AF recurrence on or off AADs during the initial 6-week blanking period is a strong independent predictor of long-term AF recurrence. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00408200.