Oral Anticoagulation Therapy in Atrial Fibrillation Patients Managed in the Emergency Department Compared to Cardiology Outpatient: Opportunities for Improved Outcomes.

INTRODUCTION: Recent registry data suggests oral anticoagulation (OAC) usage remains suboptimal in atrial fibrillation (AF) patients. The aim of our study was to determine if rates of appropriate use of OAC in individuals with AF differs between the emergency department (ED) and cardiac outpatient clinic (CO). METHODS: This was a retrospective study of consecutive AF patients over a 12-month period. Data from clinical records, discharge summaries and outpatient letters were independently reviewed by two investigators. Appropriateness of OAC was assessed according to the CHA2DS2-VASc score. RESULTS: Of 455 unique ED presentations with AF as a primary diagnosis, 115 patients who were treated and discharged from the ED were included. These were compared to 259 consecutively managed AF patients from the CO. Inappropriate OAC was significantly higher in the ED compared to the CO group (65 vs. 18%, p<0.001). Treatment in the ED was a significant multivariate predictor of inappropriate OAC (odds ratio 8.2 [4.8-17.7], p<0.001). CONCLUSIONS: This patient level data highlights that significant opportunity exists to improve disparities in the use of guideline adherent therapy in the ED compared to CO. There is an urgent need for protocol-driven treatment in the ED or streamlined early follow-up in a specialised AF clinic to address this treatment gap.

Outcomes of persistent and long-standing persistent atrial fibrillation ablation: a systematic review and meta-analysis.

Aims: Several techniques have been utilized for the ablation of persistent (P) and long-standing persistent (LsP) atrial fibrillation (AF); however, the best approach of substrate ablation remains poorly defined. This study aims to examine the impact of ablation approach on outcomes associated with P or LsP AF ablation by conducting a meta-analysis and regression on contemporary literature. Methods and results: A systematic literature review was conducted up to 29 July 2015 for scientific literature reporting on outcomes associated with P or LsP AF ablation. One hundred and thirteen studies reported outcomes in a total of 18 657 patients undergoing various ablation approaches for the treatment of P-LsP AF between 2001 and 2015. The point efficacy estimate of a single-AF ablation procedure without the use of anti-arrhythmic drugs was 43% (95% CI; 39-47%). Multiple procedures and/or the use of anti-arrhythmic drugs increase success to 69% (95% CI; 66-71%). Meta-regression revealed that ablation technique (P < 0.001) and left atrial size (P = 0.02) were predictive of single procedure, drug-free success. The addition of extra-pulmonary substrate approaches was associated with declining efficacy when compared to a pulmonary vein ablation alone. Conclusion: The efficacy of a single-AF ablation procedure for P or LsP AF is 43%; however, can be increased to 69% with the use of multiple procedures and/or anti-arrhythmic drugs. Current literature supports the finding that pulmonary vein antrum ablation/isolation is at least equivalently efficacious to other contemporary P-LsP ablation strategies.

Venturing into ventricular arrhythmia storm: a systematic review and meta-analysis.

Ablation has substantial evidence base in the management of ventricular arrhythmia (VA). It can be a 'lifesaving' procedure in the acute setting of VA storm. Current reports on ablation in VA storm are in the form of small series and have relative small representation in a large observational series. The purpose of this study was to systematically synthesize the available literature to appreciate the efficacy and safety of ablation in the setting of VA storm. The medical electronic databases through 31 January 2012 were searched. Ventricular arrhythmia storm was defined as recurrent (≥ 3 episodes or defibrillator therapies in 24 h) or incessant (continuous >12 h) VA. Studies reporting data on VA storm patients at the individual or study level were included. A total of 471 VA storm patients from 39 publications were collated for the analysis. All VAs were successfully ablated in 72% [95% confidence interval (CI) 71-89%] and 9% (95% CI: 3-10%) had a failed procedure. Procedure-related mortality occurred in three patients (0.6%). Only 6% patients had a recurrence of VA storm. The recurrence of VA was significantly higher after ablation for arrhythmic storm of monomorphic ventricular tachycardia (VT) relative to ventricular fibrillation or polymorphic VT with underlying cardiomyopathy (odds ratio 3.76; 95% CI: 1.65-8.57; P = 0.002). During the follow-up (61 ± 37 weeks), 17% of patients died (heart failure 62%, arrhythmias 23%, and non-cardiac 15%) with 55% deaths occurring within 12 weeks of intervention. The odds of death were four times higher after a failed procedure compared with those with a successful procedure (95% CI: 2.04-8.01, P < 0.001). Ventricular arrhythmia storm ablation has high-acute success rates, with a low rate of recurrent storms. Heart failure is the dominant cause of death in the long term. Failure of the acute procedure carries a high mortality.

Coronary Sinus Isolation for High-Burden Atrial Fibrillation: A Randomized Clinical Trial.

BACKGROUND: The coronary sinus is an arrhythmogenic structure that can initiate and maintain atrial fibrillation (AF). Coronary sinus ablation has been shown to be effective in prolonging the AF cycle length and terminating AF in patients with both paroxysmal and persistent AF who have persistent AF after pulmonary vein isolation (PVI). OBJECTIVES: The objective of this study was to undertake a randomized controlled trial to investigate the efficacy of coronary sinus isolation (CSI) as an adjunctive ablation strategy for the treatment of high-burden AF. METHODS: Consecutive patients presenting with symptomatic long episodes of paroxysmal AF (≥48 h but ≤7 days) or persistent AF (>7 days and ≤12 months) referred for first-time ablation were enrolled. Participants were randomized to either PVI, roofline ablation, and CSI (CSI group) or PVI and roofline ablation only (non-CSI group). Participants were assessed postprocedurally via clinical follow-up and 7-day Holter monitoring at regular intervals. The primary outcome was single-procedure drug-free atrial arrhythmia-free survival at 2 years. RESULTS: One hundred participants were recruited to the study; 48 were randomized to the CSI group and 52 to the non-CSI group. Acutely successful CSI was achieved in 45 of the 48 patients in the CSI group. At 2 years follow up, 30 of 48 patients (62.5%) in the CSI group and 33 of 52 (63.4%) in the non-CSI group were free from arrhythmia recurrence. Single-procedure drug-free survival at 2 years was no different between groups (P = 0.91). Similarly, multiple procedure drug assisted survival at 5 years was not different between groups (P = 0.80). Complication rates were not significantly different between groups (P = 0.19). CONCLUSIONS: Adjunctive CSI as part of a de novo ablation strategy does not confer any additional benefit greater than PVI and roofline for the treatment of high-burden AF.

Cardiovascular magnetic resonance of total and atrial pericardial adipose tissue: a validation study and development of a 3 dimensional pericardial adipose tissue model.

BACKGROUND: Recently pericardial adipose tissue (PAT) has been shown to be an independent predictor of atrial fibrillation (AF). Atrial PAT may influence underlying atrial musculature creating a substrate for AF. This study sought to validate the assessment of total and atrial PAT by standard cardiovascular magnetic resonance (CMR) measures and describe and validate a three dimensional atrial PAT model. METHODS: 10 merino cross sheep underwent CMR using a 1.5 Tesla system (Siemens, Sonata, Erlangen, Germany). Atrial and ventricular short axis (SA) images were acquired, using ECG -gated steady state free precession sequences. In order to quantify total volume of adipose tissue, a three dimensional model was constructed from consecutive end-diastolic images using semi-automated software. Regions of adipose tissue were marked in each slice followed by linear interpolation of pixel intensities in spaces between consecutive image slices. Total volume of adipose tissue was calculated as a total volume of the three dimensional model and the mass estimated from volume measurements. The sheep were euthanized and pericardial adipose tissue was removed and weighed for comparison to the corresponding CMR measurements. RESULTS: All CMR adipose tissue estimates significantly correlated with autopsy measurements (ICC > 0.80; p < 0.03). Intra- observer reliability in CMR measures was high, with 95% levels of agreement within 5.5% (ICC = 0.995) for total fat mass and its individual atrial (95% CI ± 8.3%, ICC = 0.993) and ventricular components (95% CI ± 6.6%, ICC = 0.989). Inter- observer 95% limits of agreement were within ± 10.7% (ICC = 0.979), 7.4% (ICC = 0.991) and 7.2% (ICC = 0.991) for atrial, ventricular and total pericardial adipose tissue, respectively. CONCLUSION: This study validates the use of a semi-automated three dimensional atrial PAT model utilizing standard (clinical) CMR sequences for accurate and reproducible assessment of atrial PAT. The measurement of local cardiac fat stores via this methodology could provide a sensitive tool to examine the regional effect of fat deposition on atrial substrate which potentially may influence AF ablation strategies in obese patients.

Effect of weight reduction and cardiometabolic risk factor management on symptom burden and severity in patients with atrial fibrillation: a randomized clinical trial.

IMPORTANCE: Obesity is a risk factor for atrial fibrillation. Whether weight reduction and cardiometabolic risk factor management can reduce the burden of atrial fibrillation is not known. OBJECTIVE: To determine the effect of weight reduction and management of cardiometabolic risk factors on atrial fibrillation burden and cardiac structure. DESIGN, SETTING, AND PATIENTS: Single-center, partially blinded, randomized controlled study conducted between June 2010 and December 2011 in Adelaide, Australia, among overweight and obese ambulatory patients (N = 150) with symptomatic atrial fibrillation. Patients underwent a median of 15 months of follow-up. INTERVENTIONS: Patients were randomized to weight management (intervention) or general lifestyle advice (control). Both groups underwent intensive management of cardiometabolic risk factors. MAIN OUTCOMES AND MEASURES: The primary outcomes were Atrial Fibrillation Severity Scale scores: symptom burden and symptom severity. Scores were measured every 3 months from baseline to 15 months. Secondary outcomes performed at baseline and 12 months were total atrial fibrillation episodes and cumulative duration measured by 7-day Holter, echocardiographic left atrial area, and interventricular septal thickness. RESULTS: Of 248 patients screened, 150 were randomized (75 per group) and underwent follow-up. The intervention group showed a significantly greater reduction, compared with the control group, in weight (14.3 and 3.6 kg, respectively; P < .001) and in atrial fibrillation symptom burden scores (11.8 and 2.6 points, P < .001), symptom severity scores (8.4 and 1.7 points, P < .001), number of episodes (2.5 and no change, P = .01), and cumulative duration (692-minute decline and 419-minute increase, P = .002). Additionally, there was a reduction in interventricular septal thickness in the intervention and control groups (1.1 and 0.6 mm, P = .02) and left atrial area (3.5 and 1.9 cm2, P = .02). CONCLUSIONS AND RELEVANCE: In this study, weight reduction with intensive risk factor management resulted in a reduction in atrial fibrillation symptom burden and severity and in beneficial cardiac remodeling. These findings support therapy directed at weight and risk factors in the management of atrial fibrillation. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12610000497000.

Device-detected atrial fibrillation in a large remote-monitored cohort: implications for anticoagulation and need for new pathways of service delivery.

BACKGROUND: Remote monitoring (RM) can facilitate early detection of subclinical and symptomatic atrial fibrillation (AF), providing an opportunity to evaluate the need for stroke prevention therapies. We aimed to characterize the burden of RM AF alerts and its impact on anticoagulation of patients with device-detected AF. METHODS: Consecutive patients with a cardiac implantable electronic device, at least one AF episode, undergoing RM were included and assigned an estimated minimum CHA2DS2-VASc score based on age and device type. RM was provided via automated software system, providing rapid alert processing by device specialists and systematic, recurrent prompts for anticoagulation. RESULTS: From 7651 individual, 389,188 AF episodes were identified, 3120 (40.8%) permanent pacemakers, 2260 (29.5%) implantable loop recorders (ILRs), 987 (12.9%) implantable cardioverter defibrillators, 968 (12.7%) cardiac resynchronization therapy (CRT) defibrillators, and 316 (4.1%) CRT pacemakers. ILRs transmitted 48.8% of all AF episodes. At twelve-months, 3404 (44.5%) AF < 6 min, 1367 (17.9%) 6 min-6 h, 1206 (15.8%) 6-24 h, and 1674 (21.9%) ≥ 24 h. A minimum CHA2DS2-VASc score of 2 was assigned to 1704 (63.1%) of the patients with an AF episode of ≥ 6 h, 531 (31.2%) who were not anticoagulated at 12-months, and 1031 (61.6%) patients with an AF episode duration of ≥ 24 h, 290 (28.1%) were not anticoagulated. CONCLUSIONS: Despite being intensively managed via RM software system incorporating cues for anticoagulation, a substantial proportion of patients with increased stroke risk remained unanticoagulated after a device-detected AF episode of significant duration. These data highlight the need for improved clinical response pathways and an integrated care approach to RM. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry: ACTRN12620001232921.

Direction-dependent conduction abnormalities in the chronically stretched atria.

AIMS: There is increasing evidence of the role direction-dependent conduction plays in the arrhythmogenic interaction between ectopic triggers and abnormal atrial substrates. We thus sought to characterize direction-dependent conduction in chronically stretched atria. METHODS AND RESULTS: Twenty-four patients with chronic atrial stretch due to mitral stenosis and 24 reference patients with left-sided accessory pathways were studied. Multipolar catheters placed at the lateral right atrium, crista terminalis, and coronary sinus (CS) characterized direction-dependent conduction along linear catheters and across the crista terminalis. Bi-atrial electroanatomic maps were created in both sinus rhythm and an alternative wavefront direction by pacing from the distal CS. This allowed an assessment of conduction velocities, electrogram, and voltage characteristics during wavefronts propagating in different directions.  While differing wavefront directions caused changes in both chronic atrial stretch and reference patients (P< 0.001 for all), these direction-dependent changes were greater in chronic atrial stretch compared with reference patients, who exhibited greater slowing in conduction velocities (P= 0.09), prolongation of bi-atrial activation time (P= 0.04), increase in number (P< 0.001) and length (P< 0.001) of lines of conduction block, increase in fractionated electrograms (P< 0.001), and decrease in voltage (P= 0.08) during left-to-right compared with right-to-left atrial activation. These direction-dependent changes were associated with a greater propensity for chronically stretched atria to develop atrial fibrillation (P= 0.02). CONCLUSIONS: Atrial remodelling in chronic atrial stretch exacerbates physiological direction-dependent conduction characteristics. Our data suggest that the greater direction-dependent conduction seen in patients with chronic atrial stretch may promote arrhythmogenesis due to ectopic triggers from the left atrium.

Remote Monitoring Alert Burden: An Analysis of Transmission in >26,000 Patients.

OBJECTIVES: This study sought to determine the remote monitoring (RM) alert burden in a multicenter cohort of patients with a cardiac implantable electronic device (CIED). BACKGROUND: RM of CIEDs allows timely recognition of patient and device events requiring intervention. Most RM involves burdensome manual workflow occurring exclusively on weekdays during office hours. Automated software may reduce such a burden, streamlining real-time alert responses. METHODS: We retrospectively analyzed 26,713 consecutive patients with a CIED undergoing managed RM utilizing PaceMate software between November 2018 and November 2019. Alerts were analyzed according to type, acuity (red indicates urgent, and yellow indicates nonurgent) and CIED category. RESULTS: In total, 12,473 (46.7%) patients had a permanent pacemaker (PPM), 9,208 (34.5%) had an implantable cardioverter-defibrillator (ICD), and 5,032 (18.8%) had an implantable loop recorder (ILR). Overall, 82,797 of the 205,804 RM transmissions were alerts, with the remainder being scheduled transmissions. A total of 14,638 (54.8%) patients transmitted at least 1 alert. Permanent pacemakers were responsible for 25,700 (31.0%) alerts, ICDs for 15,643 (18.9%) alerts, and ILRs for 41,454 (50.1%) alerts, with 3,935 (4.8%) red alerts and 78,862 (95.2%) yellow alerts. ICDs transmitted 2,073 (52.7%) red alerts; 5,024 (32.1%) ICD alerts were for ventricular tachyarrhythmias and antitachycardia pacing/shock delivery. CONCLUSIONS: In an RM cohort of 26,713 patients with CIEDs, 54.8% of patients transmitted at least 1 alert during a 12-month period, totaling over 82,000 alerts. ILRs were overrepresented, and ICDs were underrepresented, in these alerts. The enormity of the number of transmissions and the growing ILR alert burden highlight the need for new management pathways for RM.

Atrial Fibrillation and Obesity: Reverse Remodeling of Atrial Substrate With Weight Reduction.

OBJECTIVES: This study sought to evaluate the effect of weight loss on the atrial substrate for atrial fibrillation (AF). BACKGROUND: Whether weight loss can reverse the atrial substrate of obesity is not known. METHODS: Thirty sheep had sustained obesity induced by ad libitum calorie-dense diet over 72 weeks. Animals were randomized to 3 groups: sustained obesity and 15% and 30% weight loss. The animals randomized to weight loss underwent weight reduction by reducing the quantity of hay over 32 weeks. Eight lean animals served as controls. All were subjected to the following: dual-energy x-ray absorptiometry, echocardiogram, cardiac magnetic resonance, electrophysiological study, and histological and molecular analyses (fatty infiltration, fibrosis, transforming growth factor ß1, and connexin 43). RESULTS: Sustained obesity was associated with increased left atrium (LA) pressure (p < 0.001), inflammation (p < 0.001), atrial transforming growth factor ß1 protein (p < 0.001), endothelin-B receptor expression (p = 0.04), atrial fibrosis (p = 0.01), epicardial fat infiltration (p < 0.001), electrophysiological abnormalities, and AF burden (p = 0.04). Connexin 43 expression was decreased in the obese group (p = 0.03). In this obese ovine model, 30% weight reduction was associated with reduction in total body fat (p < 0.001), LA pressure (p = 0.007), inflammation (p < 0.001), endothelin-B receptor expression (p = 0.01), atrial fibrosis (p = 0.01), increase in atrial effective refractory period (cycle length: 400 and 300 ms; p < 0.001), improved conduction velocity (cycle length: 400 and 300 ms; p = 0.01), decreased conduction heterogeneity (p < 0.001), and decreased AF inducibility (p = 0.03). Weight loss was associated with a nonsignificant reduction in epicardial fat infiltration in posterior LA (p = 0.34). CONCLUSIONS: Weight loss in an obese ovine model is associated with structural and electrophysiological reverse remodeling and a reduced propensity for AF. This provides evidence for the direct role of obesity in AF substrate and the role of weight reduction in patients with AF.

High-density mapping of the sinus node in humans: role of preferential pathways and the effect of remodeling.

INTRODUCTION: The area of the functional sinus node complex exceeds that of the anatomical sinus node; however, reasons for this discrepancy are unknown. We aimed to characterize the functional sinus node complex in health and disease with high-density simultaneous mapping. METHODS AND RESULTS: Sinus node activity was characterized in 15 reference patients after ablation for supraventricular tachycardia. A further 16 patients were studied following ablation of chronic atrial flutter to determine effects of atrial remodeling. High-density simultaneous mapping of the sinus node complex was performed using a multi-electrode array. In reference patients, distance from superior vena cava-right atrial (SVC-RA) junction to earliest activation (EA) was 4 +/- 4 mm and sinus break-out (SBO) 9 +/- 6 mm. Preferential pathways of conduction were observed between EA and SBO. For patients with flutter, these distances were greater (EA: 15 +/- 12 mm, P = 0.003; SBO: 23 +/- 11 mm, P < 0.001). Conduction time along preferential pathways was 15 +/- 5 ms for reference patients and 23 +/- 8 ms for patients with flutter (P = 0.005). Following pacing, distance from SVC-RA junction to EA and SBO lengthened to 13 +/- 8 mm (P = 0.006) and 16 +/- 10 mm (P = 0.02), respectively, in reference patients, and 19 +/- 12 mm (P = 0.045), 28 +/- 9 mm (P = 0.02) in patients with flutter. This resulted in caudal shifts in EA and SBO of 10 +/- 9 mm and 7 +/- 8 mm in reference patients but diminished shifts in patients with flutter; 4 +/- 7 mm and 4 +/- 6 mm. CONCLUSION: The functional sinus node complex demonstrates dynamic changes in activation. There are preferential pathways of conduction from sinus node to atrial myocardium. The remodeled atria demonstrate longer conduction times along preferential pathways and a restricted functional sinus node complex.

Long-term mechanical consequences of permanent right ventricular pacing: effect of pacing site.

INTRODUCTION: Long-term right ventricular apical (RVA) pacing has been associated with adverse effects on left ventricular systolic function; however, the comparative effects of right ventricular outflow tract (RVOT) pacing are unknown. Our aim was therefore to examine the long-term effects of septal RVOT versus RVA pacing on left ventricular and atrial structure and function. METHODS: Fifty-eight patients who were prospectively randomized to long-term pacing either from the right ventricular apex or RVOT septum were studied echocardiographically. Left ventricular (LV) and atrial (LA) volumes were measured. LV 2D strain and tissue velocity images were analyzed to measure 18-segment time-to-peak longitudinal systolic strain and 12-segment time-to-peak systolic tissue velocity. Intra-LV synchrony was assessed by their respective standard deviations. Interventricular mechanical delay was measured as the difference in time-to-onset of systolic flow in the RVOT and LV outflow tract. Septal A' was measured using tissue velocity images. RESULTS: Following 29 ± 10 months pacing, there was a significant difference in LV ejection fraction (P < 0.001), LV end-systolic volume (P = 0.007), and LA volume (P = 0.02) favoring the RVOT-paced group over the RVA-paced patients. RVA-pacing was associated with greater interventricular mechanical dyssynchrony and intra-LV dyssynchrony than RVOT-pacing. Septal A' was adversely affected by intra-LV dyssynchrony (P < 0.05). CONCLUSIONS: Long-term RVOT-pacing was associated with superior indices of LV structure and function compared with RVA-pacing, and was associated with less adverse LA remodeling. If pacing cannot be avoided, the RVOT septum may be the preferred site for right ventricular pacing.

Feasibility of high-density electrophysiological study using multiple-electrode array in isolated small animal atria.

1. High-density cardiac electrophysiological study (EPS) of small animal atria has been limited to optical mapping techniques, which require complex and expensive equipment setup. We aim to evaluate the feasibility of carrying out EPS in isolated atrial tissues using a custom made high-density multiple-electrode array (MEA). 2. Isolated rat atrial preparations were studied. The MEA (4 × 5 mm) consisted of 90 silver chloride coated electrodes (0.1 mm diameter, 0.5 mm pitch) and was connected to a conventional EP system yielding 80 bipolar signals. Atrial tissues were placed over the MEA in a dish bubbled with 100% oxygen and superfused with modified HEPES solution at pH 7.35 and 37°C. Then, 1 mmol of 2,3-butanedione monoxime was added to suppress motion artifacts from muscle contractions. Custom plaque analysis software was used for offline conduction analysis. 3. Isolated atrial tissues showed good viability of > 30 min, allowing ample time for complete EPS. High quality electrograms with excellent signal to noise ratio were obtained. All electrophysiological parameters showed good reproducibility: effective refractory period, conduction velocity and heterogeneity index. Tachycardia was also inducible in these normal atria. 4. The present study shows the feasibility of performing high-density EPS of small isolated atrial tissues with a conventional electrode-based technique. The MEA system is compatible with standard electrophysiology recording systems and provides a novel, inexpensive option for detailed EPS in small animal models. In particular, it presents new research avenues to further explore the mechanisms of atrial arrhythmias in various transgenic and knockout rodent models.

Characterization of cardiac remodeling in a large animal "one-kidney, one-clip" hypertensive model.

OBJECTIVE: The aim of this study is to characterize cardiac remodeling in a large animal model of hypertension. METHODS: 23 sheep were subjected to unilateral nephrectomy followed by clamping of the remaining renal artery to 60% ("one kidney-one clip", 1K1C) 3 weeks later. Blood pressure (BP) was monitored invasively over 73+/-28 days. Cardiac function was assessed with magnetic resonance imaging and compared with 12 size-matched controls. Detailed atrial histopathological analysis was performed. RESULTS: In the 1K1C animals, BP rose from baseline to reach a plateau by 4 weeks (systolic BP: 107+/-12 to 169+/-27, diastolic BP: 71+/-10 to 118+/-29 mmHg, both p< 0.0001); cardiac hypertrophy was significant when compared with controls with increased left ventricular weight [left ventricular (LV)/body wt: 2.7+/-0.5 vs 2.1+/-0.2 g/kg, p=0.01] as well as bi-atrial enlargement (right atrial, RA: 22.9+/-4.9 vs 15.7+/-2.8g, p=0.003; left atrial, LA: 35.5+/-6.7 vs 20.9+/-4.1g, p=0.0003); cardiac magnetic imaging demonstrated significantly increased LA volumes (end-diastolic volume: 42.9+/-6.8 vs 28.7+/-6.3 ml, p< 0.0001) and reduced LA ejection fraction (24.1+/-3.6 vs 31.6+/-3.0%, p=0.001) while LV function was relatively preserved (42.3+/-4.7 vs 46.4+/-4.1%, p=0.1); degeneration and necrosis of atrial myocytes were evident with increased atrial lymphocytic infiltration and interstitial fibrosis. CONCLUSIONS: The ovine 1K1C model produces reliable and reproducible hypertension with demonstrable cardiac end-organ damage.

Cerebral Blood Flow and Cognitive Performance in Postural Tachycardia Syndrome: Insights from Sustained Cognitive Stress Test.

Background The physiology underlying "brain fog" in the absence of orthostatic stress in postural tachycardia syndrome (POTS) remains poorly understood. Methods and Results We evaluated cognitive and hemodynamic responses (cardiovascular and cerebral: heart rate, blood pressure, end-tidal carbon dioxide, and cerebral blood flow velocity (CBFv) in the middle cerebral artery at baseline, after initial cognitive testing, and after (30-minutes duration) prolonged cognitive stress test (PCST) whilst seated; as well as after 5-minute standing in consecutively enrolled participants with POTS (n=22) and healthy controls (n=18). Symptom severity was quantified with orthostatic hypotensive questionnaire at baseline and end of study. Subjects in POTS and control groups were frequency age- and sex-matched (29±11 versus 28±13 years; 86 versus 72% women, respectively; both P≥0.4). The CBFv decreased in both groups (condition, P=0.04) following PCST, but a greater reduction in CBFv was observed in the POTS versus control group (-7.8% versus -1.8%; interaction, P=0.038). Notably, the reduced CBFv following PCST in the POTS group was similar to that seen during orthostatic stress (60.0±14.9 versus 60.4±14.8 cm/s). Further, PCST resulted in greater slowing in psychomotor speed (6.1% versus 1.4%, interaction, P=0.027) and a greater increase in symptom scores at study completion (interaction, P<0.001) in the patients with POTS, including increased difficulty with concentration. All other physiologic responses (blood pressure and end-tidal carbon dioxide) did not differ between groups after PCST (all P>0.05). Conclusions Reduced CBFv and cognitive dysfunction were evident in patients with POTS following prolonged cognitive stress even in the absence of orthostatic stress.

Home-Based Education and Learning Program for Atrial Fibrillation: Rationale and Design of the HELP-AF Study.

BACKGROUND: Atrial fibrillation (AF) is a growing global epidemic, with its prevalence expected to significantly rise over coming decades. AF poses a substantial burden on health care systems, largely due to hospitalizations. Home-based clinical characterization has demonstrated improved outcomes in cardiac populations, but its impact on AF remains poorly defined. To test this hypothesis in AF, we developed the Home-Based Education and Learning Program for Patients With Atrial Fibrillation (HELP-AF) study. METHODS: The HELP-AF study is a prospective multicentre randomized controlled trial that will recruit 620 patients presenting to hospital emergency departments (EDs) with symptomatic AF (ANZCTR Registration: ACTRN12611000607976). Patients will be randomized to either the HELP-AF intervention or usual care. The intervention consists of 2 home visits by a nurse or pharmacist trained in the structured educational visiting (SEV) method. Patients in the control group will receive usual discharge follow-up care. RESULTS: The primary endpoints are total unplanned hospital admissions and quality of life. Secondary endpoints include AF symptom severity and burden score; time to first hospital admission; total unplanned days in hospital; total AF-related hospital admissions (including atrial flutter); total cardiac and noncardiac hospital admissions; total AF- or atrial flutter-related; cardiac- and noncardiac-related ED presentations; and all-cause mortality. An economic evaluation will also be performed. Clinical endpoints will be adjudicated by independent blinded assessors. Follow-up will be at 24 months. CONCLUSIONS: This study will assess the efficacy of a home-based structured patient-centred educational intervention in patients with AF.

Patient-Centered Educational Resources for Atrial Fibrillation.

Education has long been recognized as an important component of chronic condition management. Whereas education has been evaluated in atrial fibrillation (AF) populations as part of multifaceted interventions, it has never been tested as a single entity. The aim of this review is to describe the rationale for and role of education as part of comprehensive AF management. The development and use of educational material as part of the intervention of a randomized controlled trial, the HELP-AF (Home-Based Education and Learning Program in AF) study, will be described. This study was designed to determine the impact of a home-based structured educational program on outcomes in individuals with AF. An educational resource was developed to facilitate delivery of 4 key messages targeted at empowering individuals to self-manage their condition. The key messages focused on strategies for managing future AF episodes, the role of pharmacotherapy in the treatment of AF, the appropriate use of medicines to manage stroke risk and the role of cardiovascular risk factor management in AF. To support structured educational visiting, an educational booklet titled Living Well With Atrial Fibrillation (AF) was developed by a multidisciplinary team and was further refined following input from expert clinicians and patient interviews. Using a structured educational visiting approach, education was delivered by trained clinicians within the patient's home.

Variability of Sleep Apnea Severity and Risk of Atrial Fibrillation: The VARIOSA-AF Study.

OBJECTIVES: This study sought to determine night-to-night variability in the severity of sleep-disordered breathing (SDB) and the dynamic intraindividual relationship to daily risk of incident atrial fibrillation (AF) by using simultaneous long-term day-by-day SDB and AF monitoring. BACKGROUND: Night-to-night variability in SDB severity may result in a dynamic exposure to SDB related conditions impacting the timing and extent of cardiovascular responses. METHODS: This study was an observational cohort study. Daily data for AF burden and average respiratory disturbance index (RDI) were extracted from pacemakers capable of monitoring nightly SDB and daily AF burden in 72 patients. Nightly RDI values were grouped into quartiles of severity within each patient. AF burdens of >5 min, >1 h, and >12 h were the outcome variables. RESULTS: A total of 32% of patients had a mean RDI of ≥20/h, indicative of overall severe SDB. There was significant night-to-night variation in RDI reflected by an absolute SD of ±6.3 events/h (range 2 to 14 events/h) within any given patient. Within each patient, the nights with the highest RDI (in their highest quartile) conferred a 1.7-fold (1.2 to 2.2; p < 0.001), 2.3-fold (1.6 to 3.5; p < 0.001), and 10.2-fold (3.5 to 29.9; p < 0.001) increase risk of having at least 5 min, 1 h, and 12 h, respectively, of AF during the same day compared with the best sleep nights (in their lowest quartiles). CONCLUSIONS: There is considerable night-to-night variability in SDB severity which cannot be detected by 1 single overnight sleep study. SDB burden may be a better metric with which to assess the extent of dynamic SDB related cardiovascular responses such as daily AF risk than the categorical diagnosis of SDB. (Night-to-Night Variability in Severity of Sleep Apnea and Daily Dynamic Atrial Fibrillation Risk [VARIOSA-AF]; ACTRN 12618000757213).

The effect of electrogram duration on quantification of complex fractionated atrial electrograms and dominant frequency.

INTRODUCTION: Sites of complex fractionated atrial electrograms (CFAEs) and highest dominant frequency (DF) have been proposed as critical regions maintaining atrial fibrillation (AF). This study aimed to determine the minimum electrogram recording duration that accurately characterizes CFAE or DF sites for ablation without unduly lengthening the procedure. METHODS AND RESULTS: Fourteen patients with AF undergoing catheter ablation had high-density (498 +/- 174 points) biatrial mapping performed during AF before ablation. At each point, 8-second electrograms were recorded. CFAE characterization using the NavX software provided a representation of electrogram complexity (CFE-mean). CFE-mean for each point from 7-, 6-, 5-, 4-, 3-, 2-, and 1-second subsamples were compared with the index 8-second CFE-mean. Offline spectral analysis defined DF as the frequency with greatest power, and DF of subsamples were compared with index DF. Index 8-second electrogram CFE-mean was 114 +/- 20 ms for right atria and 102 +/- 17 ms for left atria (P = 0.01); DF was 5.7 +/- 0.8 Hz for right atria and 6.0 +/- 0.8 Hz for left atria (P = 0.02). Means from shorter electrograms were nonsignificantly decreased for CFE-mean and overestimated for DF (P < 0.001). Mean absolute differences between subsampled and index values ranged from 3.3 to 20.1 ms for CFE-mean and 0.11 to 1.18 Hz for DF. Subsampled electrograms deviating >10% from index values ranged from 2.5 to 56% for CFE-mean and 3.5 to 41% for DF. Intraclass correlation coefficients ranged from 0.992 to 0.788 for CFE-mean and 0.897 to 0.233 for DF. Unacceptable differences from index values were found with CFE-mean and DF from electrograms <5 seconds. CONCLUSION: Electrograms of >or=5-second duration are required to accurately characterize CFAE and DF sites for ablation.

High-density mapping of atrial fibrillation in humans: relationship between high-frequency activation and electrogram fractionation.

INTRODUCTION: Sites of complex fractionated atrial electrograms (CFAE) and dominant frequency (DF) have been implicated in maintaining atrial fibrillation (AF); however, their relationship is poorly understood. METHODS AND RESULTS: Twenty patients underwent biatrial high-density contact mapping (507 +/- 150 points/patient) during AF. CFAE were characterized using software to quantify electrogram complexity (CFE-mean). Spectral analysis determined the frequency with greatest power and sites of high DF with a frequency gradient. CFE-mean was higher (less fractionated) for right compared with left atria (P < 0.001) and in paroxysmal compared with persistent AF (P < 0.001). DF was lower for right compared with left atria (P = 0.02) and in paroxysmal compared with persistent AF (P < 0.001). There was significant regional variation in DF in paroxysmal (P < 0.001) but not persistent AF. Highest DF points clustered together with 5.2 +/- 1.7 clusters/patient. Correlation between CFE-mean and DF was poor on a point-by-point basis (r =-0.17, P < 0.001), but moderate on an individual basis (r =-0.50, P = 0.03). Exploration of their spatial relationship demonstrated CFAE areas in close proximity (median 5 mm, IQR 2-10) to high DF sites; within 10 mm in 80% and 10-20 mm in 10%. Simultaneous activation mapping at these sites further supports this observation. CONCLUSION: Greater fractionation and higher DF are seen in persistent AF and left atria during AF. Preferential areas of high DF are observed in paroxysmal but not persistent AF. CFAE and DF correlate within an individual but not point-by-point. Exploration of their spatial relationship demonstrates CFAE in areas adjacent to high DF, and this is supported by activation mapping at these sites.