Factors affecting electrogram sensing in an insertable cardiac monitor: Insights from surface electrocardiogram mapping analysis.

BACKGROUND: Fidelity of electrogram sensing may reduce false alerts from an insertable cardiac monitor (ICM). OBJECTIVE: The purpose of this study was to assess the effect of vector length, implant angle, and patient factors on electrogram sensing using surface electrocardiogram (ECG) mapping. METHODS: Twelve separate precordial single-lead surface ECGs were acquired from 150 participants at 2 interelectrode distances (75 and 45 mm), at 3 vector angles (vertical, oblique, and horizontal), and in 2 postures (upright and supine). A subset of 50 patients also received a clinically indicated ICM implant in 1:1 ratio (Reveal LINQ [Medtronic, Minneapolis, MN]/BIOMONITOR III [Biotronik, Berlin, Germany]). All ECGs and ICM electrograms were analyzed by blinded investigators using DigitizeIt software (V2.3.3, Braunschweig, Germany). The P-wave visibility threshold was set at > 0.015 mV. Logistic regression was used to identify factors affecting P-wave amplitude. RESULTS: A total of 1800 tracings from 150 participants (44.5% [n = 68] female; median age 59 [35-73] years) were assessed. The median P- and R-wave amplitudes were 45% and 53% larger with vector lengths of 75 and 45 mm, respectively (P < .001 for both). The oblique orientation yielded the best P- and R-wave amplitudes, while posture change did not affect P-wave amplitude. Mixed effects modeling found that visible P-waves occur more frequently with a vector length of 75 mm than with 45 mm (86% vs 75%, respectively; P < .0001). A longer vector length improved both P-wave amplitude and visibility in all body mass index categories. There was a moderate correlation of P- and R-wave amplitudes from the ICM electrograms to those from surface ECG recordings (intraclass correlation coefficient 0.74 and 0.80, respectively). CONCLUSION: Longer vector length and oblique implant angle yielded the best electrogram sensing and are relevant considerations for ICM implantation procedures.

The Burden of Cardiac Implantable Electronic Device Checks in the Peri-MRI Setting: The CHECK-MRI Study.

BACKGROUND: Most modern cardiac implantable electronic device (CIED) systems are now compatible with magnetic resonance imaging (MRI) scans. The requirement for both pre- and post-MRI CIED checks imposes significant workload to the cardiac electrophysiology service. Here, we sought to determine the burden of CIED checks associated with MRI scans. METHODS: We identified all CIED checks performed peri-MRI scans at our institution over a 3-year period between 1 July 2017 to 30 June 2020, comprising three separate financial years (FY). Device check reports, MRI scan reports and clinical summaries were collated. The workload burden was determined by assessing the occasions and duration of service. Analysis was performed to determine cost burden/projections for this service and identify factors contributing to the workload. RESULTS: A total of 739 CIED checks were performed in the peri-MRI scan setting (370 pre- and 369 post-MRI scan), including 5% (n=39) that were performed outside of routine hours (weekday <8 am or >5 pm, and weekends). MRIs were performed for 295 patients (75±13 years old, 64% male) with a CIED (88% permanent pacemaker, and 12% high voltage device), including 49 who had more than one MRI scan. The proportion of total MRI scans for patients with a CIED in-situ increased each FY (from 0.5% of all MRIs in FY1, to 0.9% in FY2, to 1.0% in FY3). The weekly workload increased (R2=0.2, p<0.001), but with week-to-week variability due to ad hoc scheduling (209 days with only one MRI vs 78 days with ≥2 MRIs for CIED patients). The projected annual cost of this service will increase to AUD$161,695 in 10 years for an estimated annual 546 MRI scans for CIED patients. CONCLUSIONS: There is an increasing workload burden and expense associated with CIED checks in the peri-MRI setting. Appropriate budgeting, staff allocation and standardisation of automated CIED pre-programming features among manufacturers are urgently needed.

Impact of device length on electrogram sensing in miniaturized insertable cardiac monitors.

BACKGROUND: Little data exists on electrogram sensing in current generation of miniaturized insertable cardiac monitors (ICMs). OBJECTIVE: To compare the sensing capability of ICM with different vector length: Medtronic Reveal LINQ (~40 mm) vs. Biotronik Biomonitor III (BM-III, ~70 mm). METHODS: De-identified remote monitoring transmissions from n = 40 patients with BM-III were compared with n = 80 gender and body mass index (BMI)-matched patients with Reveal LINQ. Digital measurement of P- and R-wave amplitude from calibrated ICM electrograms was undertaken by 3 investigators independently. Further, we evaluated the impact of BMI and gender on P-wave visibility. RESULTS: Patients in both groups were well matched for gender and BMI (53% male, mean BMI 26.7 kg/m2, both p = NS). Median P- and R-wave amplitude were 97% & 56% larger in the BM-III vs. LINQ [0.065 (IQR 0.039-0.10) vs. 0.033 (IQR 0.022-0.050) mV, p < .0001; & 0.78 (IQR 0.52-1.10) vs. 0.50 (IQR 0.41-0.89) mV, p = .012 respectively). The P/R-wave ratio was 36% greater with the BM-III (p < .001). The 25th percentile of P-wave amplitude for all 120 patients was .026 mV. Logistic regression analysis showed BM-III was more likely than LINQ to have P-wave amplitude ≥.026 mV (OR 7.47, 95%CI 1.965-29.42, p = .003), and increasing BMI was negatively associated with P-wave amplitude ≥.026 mV (OR 0.84, 95%CI 0.75-0.95, p = .004). However, gender was not significantly associated with P-wave amplitude ≥.026 mV (p = .37). CONCLUSION: The longer ICM sensing vector of BM-III yielded larger overall P- and R- wave amplitude than LINQ. Both longer sensing vector and lower BMI were independently associated with greater P-wave visibility.

Autonomic Afferent Dysregulation in Atrial Fibrillation.

OBJECTIVES: This study sought to evaluate the role of cardiac afferent reflexes in atrial fibrillation (AF). BACKGROUND: Efferent autonomic tone is not associated with atrial remodeling and AF persistence. However, the role of cardiac afferents is unknown. METHODS: Individuals with nonpermanent AF (n = 48) were prospectively studied (23 in the in-AF group and 25 in sinus rhythm [SR]) with 12 matched control subjects. We performed: 1) low-level lower body negative pressure (LBNP), which decreases cardiac volume, offloading predominantly cardiac afferent (volume-sensitive) low-pressure baroreceptors; 2) Valsalva reflex (predominantly arterial high-pressure baroreceptors); and 3) isometric handgrip reflex (both baroreceptors). We measured beat-to-beat mean arterial pressure (MAP) and heart rate (HR). LBNP elicits reflex vasoconstriction, estimated using venous occlusion plethysmography-derived forearm blood flow (∝1/vascular resistance), maintaining MAP. To assess reversibility, we repeated LBNP (same day) after 1-hour low-level tragus stimulation (in n = 5 in the in-AF group and n = 10 in the in-SR group) and >6 weeks post-cardioversion (n = 7). RESULTS: The 3 groups were well matched for age (59 ± 12 years, 83% male), body mass index, and risk factors (P = NS). The in-AF group had higher left atrial volume (P < 0.001) and resting HR (P = 0.01) but similar MAP (P = 0.7). The normal LBNP vasoconstriction (-49 ± 5%) maintaining MAP (control subjects) was attenuated in the in-SR group (-12 ± 9%; P = 0.005) and dysfunctional in the in-AF group (+11 ± 6%; P < 0.001), in which MAP decreased and HR was unchanged. Valsalva was normal throughout. Handgrip MAP response was lowest in the in-AF group (P = 0.01). Interestingly, low-level tragus stimulation and cardioversion improved LBNP vasoconstriction (-48 ± 15%; P = 0.04; and -32 ± 9%; P = 0.02, respectively). CONCLUSIONS: Cardiac afferent (volume-sensitive) reflexes are abnormal in AF patients during SR and dysfunctional during AF. This could contribute to AF progression, thus explaining "AF begets AF." (Characterisation of Autonomic function in Atrial Fibrillation [AF-AF Study]; ACTRN12619000186156).

Rationale and design of the IRON-AF study: a double-blind, randomised, placebo-controlled study to assess the effect of intravenous ferric carboxymaltose in patients with atrial fibrillation and iron deficiency.

INTRODUCTION: Atrial fibrillation (AF) is associated with significantly impaired quality-of-life. Iron deficiency (ID) is prevalent in patients with AF. Correction of ID in other patient populations with intravenous iron supplementation has been shown to be a safe, convenient and effective way of improving exercise tolerance, fatigue and quality-of-life. The IRON-AF (Effect of Iron Repletion in Atrial Fibrillation) study is designed to assess the effect of iron repletion with intravenous ferric carboxymaltose in patients with AF and ID. METHODS AND ANALYSIS: The IRON-AF study is a double-blind, randomised controlled trial that will recruit at least 84 patients with AF and ID. Patients will be randomised to receive infusions of either ferric carboxymaltose or placebo, given in repletion and then maintenance doses. The study will have follow-up visits at weeks 4, 8 and 12. The primary endpoint is change in peak oxygen uptake from baseline to week 12, as measured by cardiopulmonary exercise testing (CPET) on a cycle ergometer. Secondary endpoints include changes in quality-of-life and AF disease burden scores, blood parameters, other CPET parameters, transthoracic echocardiogram parameters, 6-minute walk test distance, 7-day Holter/Event monitor burden of AF, health resource utilisation and mortality. ETHICS AND DISSEMINATION: The study protocol has been approved by the Central Adelaide Local Health Network Human Research Ethics Committee, Australia. The results of this study will be disseminated through publications in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12620000285954).

Left atrial, pulmonary vein, and left atrial appendage anatomy in Indigenous individuals: Implications for atrial fibrillation.

BACKGROUND: Indigenous Australians experience a greater burden of AF. Whether this is in-part due to differences in arrhythmogenic structures that appear to contribute to AF differences amongst other ethnicities is not known. METHODS: We studied forty individuals matched for ethnicity and other AF risk factors. Computed tomography imaging was used to characterise left atrial (LA), pulmonary vein (PV), and left atrial appendage (LAA) anatomy. RESULTS: There were no significant differences in LA diameters or volumes between Indigenous and non-Indigenous Australians. Similarly, we could not detect any consistent differences in PV number, morphology, diameters, or ostial characteristics according to ethnicity. LAA analyses suggested that Indigenous Australians may have a greater proportion of non chickenwing LAA type, and a tendency for eccentric, oval-shaped LAA ostia; however, there were no other differences seen with regards to LAA volume or depth. Indexed values for LA, PV and LAA anatomy corrected for body size were broadly similar. CONCLUSIONS: In a cohort of individuals matched for AF risk factors, we could find no strong evidence of ethnic differences in LA, PV, and LAA characteristics that may explain a predisposition of Indigenous Australians for atrial arrhythmogenesis. These findings, in conjunction with our previous data showing highly prevalent cardiometabolic risk factors in Indigenous Australians with AF, suggest that it is these conditions that are more likely responsible for the AF substrate in these individuals. Continued efforts should therefore be directed towards risk factor management in an attempt to prevent and minimise the effects of AF in Indigenous Australians.

Atrial Fibrillation in Remote Indigenous and Non-Indigenous Individuals Hospitalised in Central Australia.

BACKGROUND: The epidemiology of atrial fibrillation (AF) amongst Indigenous populations remains poorly characterised. We studied hospitalisations for AF in Central Australia, the most populous Indigenous region in the country. METHODS: Patients with a diagnosis of AF admitted to Alice Springs Hospital, the only secondary health care facility and provider of cardiac care in remote Central Australia, were identified from 2006 to 2016. Age and gender-specific hospitalised AF prevalence, comorbidities, and CHA2DS2-VASc scores were ascertained. RESULTS: Of 57,056 admitted patients over the study period, 1,210 (2.1%; 46% Indigenous) had a diagnosis of AF. For Indigenous and non-Indigenous individuals <45 years, hospitalised AF prevalence per 10,000 population was 105 (CI 84-131) and 50 (CI 36-68) in males (ratio=2.10), and 98 (CI 77-123) and 12 (CI 6-23) in females (ratio=7.92), respectively. For Indigenous and non-Indigenous individuals ≥65 years, hospitalised AF prevalence per 10,000 was 1,577 (CI 1,194-2,026) and 2,326 (CI 2,047-2,623) in males (ratio=0.68), and 1,713 (CI 1,395-2,069) and 1,897 (1,623-2,195) in females (ratio=0.90). Indigenous individuals had higher rates of cardiometabolic comorbidities, particularly at younger ages. CHA2DS2-VASc scores were greater in Indigenous individuals, particularly those <45 years (2.5±1.5 versus 0.7±1.1, p<0.001). CONCLUSIONS: The prevalence of hospitalised AF amongst Indigenous people in remote Central Australia was significantly higher than in non-Indigenous individuals, particularly in younger age groups and females. Indigenous individuals with hospitalised AF also had a markedly greater prevalence of cardiometabolic comorbidities and elevated stroke risk. These data suggest that AF may be contributing to the gap in morbidity and mortality experienced by Indigenous Australians.

Predictors of Anticoagulation Use in Indigenous and Non-Indigenous Australians With Atrial Fibrillation.

OBJECTIVE: Prior studies have demonstrated that anticoagulation underutilisation for atrial fibrillation (AF) and elevated stroke risk is common. However, there is little data on factors associated with appropriate anticoagulation, particularly in Indigenous Australians who face a disproportionate burden of AF and stroke. We thus sought to determine factors associated with anticoagulation use in Australians with AF. DESIGN: Administrative, clinical, prescriptive and laboratory data were linked and aggregated over a 12-year period. SETTING: Single tertiary teaching hospital. PARTICIPANTS: 19,305 (98%) and 308 (2%) consecutive non-Indigenous and Indigenous Australians with AF identified from administrative databases. MAIN OUTCOME MEASURES: Associations of anticoagulation use according to ethnicity. RESULTS: Significant independent predictors of anticoagulation use included hypertension (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.17-1.34; p<0.001), diabetes (OR 1.14, 95% CI 1.05-1.24; p=0.002), heart failure (OR 1.54 95% CI 1.43-1.66; p<0.001) and prior stroke or transient ischaemic attack (OR 2.07, 95% CI 1.84-2.33; p<0.001). In contrast, increasing age (OR 0.99, 95% CI 0.98-0.99; p<0.001), female gender (OR 0.88, 95% CI 0.82-0.93; p<0.001), and vascular disease (OR 0.72, 95% CI 0.64-0.80; p<0.001) were significant predictors of no anticoagulation. Hypertension was associated with less anticoagulation use in Indigenous compared to non-Indigenous Australians (p=0.02). CONCLUSIONS: Anticoagulation for AF was suboptimal in both Indigenous and non-Indigenous Australians. Older age, female gender, and comorbid vascular disease were found to be negatively associated with anticoagulation. Importantly, hypertension may also be under-recognised as a stroke risk factor in Indigenous Australians. Future efforts to encourage anticoagulation use in accordance with guideline recommendations is likely to reduce the burden of AF-related stroke in both Indigenous and non-Indigenous populations.

Quality of Warfarin Anticoagulation in Indigenous and Non-Indigenous Australians With Atrial Fibrillation.

BACKGROUND: Studies have shown that suboptimal anticoagulation quality, as measured by time in therapeutic range (TTR), affects a significant percentage of patients with atrial fibrillation (AF). However, TTR has not been previously characterised in Indigenous Australians who experience a greater burden of AF and stroke. METHOD: Indigenous and non-Indigenous Australians with AF on warfarin anticoagulation therapy were identified from a large tertiary referral centre between 1999 and 2012. Time in therapeutic range was calculated as a proportion of daily international normalised ratio (INR) values between 2 and 3 for non-valvular AF and 2.5 to 3.5 for valvular AF. INR values between tests were imputed using the Rosendaal technique. Linear regression models were employed to characterise predictors of TTR. RESULTS: Five hundred and twelve (512) patients with AF on warfarin were included (88 Indigenous and 424 non-Indigenous). Despite younger age (51±13 vs 71±12 years, p<0.001), Indigenous Australians had greater valvular heart disease, diabetes, and alcohol excess compared to non-Indigenous Australians (p<0.05 for all). Time in therapeutic range was significantly lower in Indigenous compared to non-Indigenous Australians (40±29 vs 50±31%, p=0.006). Univariate predictors of poorer TTR included Indigenous ethnicity, younger age, diuretic use, and comorbidities, such as valvular heart disease, heart failure and chronic obstructive pulmonary disease (p<0.05 for all). Valvular heart disease remained a significant predictor of poorer TTR in multivariate analyses (p=0.004). CONCLUSION: Indigenous Australians experience particularly poor warfarin anticoagulation quality. Our data also suggest that many non-Indigenous Australians spend suboptimal time in therapeutic range. These findings reinforce the importance of monitoring warfarin anticoagulation quality to minimise stroke risk.

Epicardial and subcutaneous adipose tissue in Indigenous and non-Indigenous individuals: Implications for cardiometabolic diseases.

BACKGROUND: Obesity is prevalent in Indigenous populations who exhibit significant differences in body fat composition. While excess regional adiposity can be partially inferred from clinical measurements, noninvasive imaging allows for direct quantification of specific fat depots. Epicardial fat is a visceral adipose tissue that has been strongly associated with cardiometabolic disease in other populations. However, this ectopic fat depot has yet to be characterized in Indigenous populations. METHODS: We studied 100 individuals matched for ethnicity (Indigenous Australian and Caucasian descent), age, gender, and body mass index. Epicardial and subcutaneous adipose tissue volumes was quantified with computed tomography. Associations of ethnicity and adiposity measures were assessed using linear regression. RESULTS: Indigenous individuals had significantly greater epicardial fat volumes compared to non-Indigenous individuals (95.8±37.5 vs 54.1±27.6cm3, p<0.001). In contrast, subcutaneous fat volumes were comparable in Indigenous compared to non-Indigenous individuals (22.1±15.1 vs 20.3±13.5cm3, p=0.54). Sequential adjustment for age, gender, comorbidities, biochemical parameters, and medication use did not attenuate the association between Indigenous ethnicity and greater epicardial fat volume in multivariable models (B=43.0, p<0.001). Furthermore, this association did not materially change with the inclusion of various adiposity measures, such as body mass index, subcutaneous adipose tissue, or weight. CONCLUSIONS: Indigenous individuals have significantly greater epicardial fat, but similar subcutaneous fat volumes, compared to non-Indigenous individuals. This finding extends previous observations on body fat composition differences in these individuals, and supports the possibility that epicardial fat and other visceral adipose depots may be contributing to the greater burden of cardiovascular disease in Indigenous populations.

Implication of ventricular pacing burden and atrial pacing therapies on the progression of atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Atrial fibrillation (AF) is common after pacemaker implantation. However, the impact of pacemaker algorithms in AF prevention is not well understood. OBJECTIVE: The purpose of this study was to evaluate the role of pacing algorithms in preventing AF progression. METHODS: A systematic search of articles using the PubMed and Embase databases resulted in a total of 754 references. After exclusions, 21 randomized controlled trials (8336 patients) were analyzed, comprising studies reporting ventricular pacing percentage (VP%) (AAI vs DDD, n = 1; reducing ventricular pacing [RedVP] algorithms, n = 2); and atrial pacing therapies (atrial preference pacing [APP], n = 14; atrial antitachycardia pacing [aATP]+APP, n = 3; RedVP+APP+aATP, n = 1). RESULTS: Low VP% (<10%) lead to a nonsignificant reduction in the progression of AF (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.57-1.13; P = .21; I2 = 67%) compared to high VP% (>10%). APP algorithm reduced premature atrial complexes (PAC) burden (mean difference [MD] -1117.74; 95% CI -1852.36 to -383.11; P = .003; I2 = 67%) but did not decrease AF burden (MD 8.20; 95% CI -5.39 to 21.80; P = .24; I2 = 17%) or AF episodes (MD 0.00; 95% CI -0.24 to 0.25; P = .98; I2 = 0%). Similarly, aATP+APP programming showed no significant difference in AF progression (odds ratio 0.65; 95% CI 0.36-1.14; P = .13; I2 = 61%). No serious adverse events related to algorithm were reported. CONCLUSION: This meta-analysis of randomized controlled trials demonstrated that algorithms to reduce VP% can be considered safe. Low burden VP% did not significantly suppress AF progression. The atrial pacing therapy algorithms could suppress PAC burden but did not prevent AF progression.

Catheter Ablation of Post-Infarct VT: Mechanisms, Strategies and Outcomes.

Ventricular arrhythmias are one of the leading causes of death in patients with a prior myocardial infarction. Implantable cardioverter-defibrillators (ICDs) are very effective in the prevention of sudden cardiac death but the risk of recurrence remains an issue since defibrillation does not alter the underlying substrate. Recurrent ICD shocks are distressing and are associated with an increase in mortality. Catheter ablation is an effective treatment for recurrent ventricular tachycardia in these patients, particularly when antiarrhythmic therapy produces side effects or is ineffective. This paper reviews the underlying mechanisms of VT in patients with a prior myocardial infarction, and the indications, strategies and outcomes of catheter ablation.

Influence of ethnic background on left atrial markers of inflammation, endothelial function and tissue remodelling.

BACKGROUND: It has been suggested that ethnicity can make a significant difference to the likelihood of thromboembolic stroke related to atrial fibrillation. Ethnic differences have been shown to alter inflammatory and haemostatic factors; however, this may all be confounded by differences in cardiovascular risk factors between different ethnicity. The impact of different ethnicities on the thrombogenic profile is not known. The aim of this study was to investigate differences in markers of inflammation, endothelial function and tissue remodelling between Caucasian and Indian populations with supraventricular tachycardia (SVT). METHODS: Patients with structurally normal hearts undergoing catheter ablation for SVT were studied. This study included 23 Australian (Caucasian) patients from the Royal Adelaide Hospital, Adelaide, Australia and 24 Indian (Indian) patients from the Christian Medical College, Vellore, India. Blood samples were collected from the femoral vein, and right and left atria. Blood samples were analysed for the markers of endothelial function (ADMA, ET-1), inflammation (CD40L, VCAM-1, ICAM-1), and tissue remodelling (MMP-9, TIMP-1) using ELISA. RESULTS: The study populations were well matched for cardiovascular risk factors and the absence of structural heart disease. No difference in the echocardiographic measurements between the two ethnicities was found. In this context, there was no difference in markers of inflammation, endothelial function or tissue remodelling between the two SVT populations. CONCLUSION: Caucasian and Indian populations demonstrate similar inflammatory, endothelial function or tissue remodelling profiles. This study suggests a lack of an impact of different ethnicity in these populations in terms of thrombogenic risk.

Electrophysiologic features of protected channels in late postinfarction patients with and without spontaneous ventricular tachycardia.

PURPOSE: Protected channels of surviving myocytes in late postinfarction ventricular scar predispose to ventricular tachycardia (VT). However, only a few patients develop VT spontaneously. We studied differences in electric remodeling and protected channels in late postinfarction patients with and without spontaneous VT. METHODS: Patients with ischemic cardiomyopathy (ICM) with recurrent sustained monomorphic VT (n = 22) were compared with stable ICM patients without spontaneous VT (control group; n = 5). Left ventricular mapping was performed with a 20-pole catheter. Detailed pace mapping was used to identify channels of protected conduction, and confirmed, when feasible, by entrainment. Anatomical and electrophysiological properties of VT channels and non-VT channels in VT patients and channels in controls were evaluated. RESULTS: Seventy-three (median 3) VTs were inducible in VT patients compared to two (median 0) in controls. The VT channels in VT patients (n = 57, 3 ± 1 per patient) were lengthier (mean ± SEM 53 ± 5 vs. 33 ± 4 vs. 24 ± 8 mm), had longer S-QRS (73 ± 4 vs. 63 ± 3 vs. 44 ± 8 ms), longer conduction time (103 ± 13 vs. 33 ± 4 vs. 24 ± 8 ms), and slower conduction velocity (CV) (0.85 ± 0.21 vs. 1.39 ± 0.20 vs. 1.31 ± 0.41 m/s) than non-VT channels in VT patients (n = 183, 8 ± 6 per patient) (p ≤ 0.01) and channels in controls (n = 46, 9 ± 8 per patient) (p ≤ 0.01). Additionally, non-VT channels in VT patients had longer S-QRS (p = 0.02); however, they were similar in length, conduction time, and CV compared to channels in controls. CONCLUSIONS: Channels supporting VT are lengthier, with longer conduction times and slower CV compared to channels in patients without spontaneous VT. These observations may explain why some ICM patients have spontaneous VT and others do not.

Atrial fibrillation and risk of hip fracture: A population-based analysis of 113,600 individuals.

BACKGROUND: A number of cardiovascular diseases have been linked with bone health and an increased risk of osteoporotic fracture. Whether atrial fibrillation (AF) is associated with subsequent fracture risk is not known. METHODS: Administrative, clinical and hospitalisation information were linked over a 14-year period. From this longitudinal, population-based dataset of 113,600 individuals, time-dependent exposures using multivariate Cox proportional hazards regression models were employed to determine incidence rates and hazard ratios (HR) for hip fracture according to a history of AF. RESULTS: The annualised incidence rate for hip fracture was 7.4 per 1000 person-years (95% CI 7.1-7.7) in those without AF and 17.5 per 1000 person-years (95% CI 16.8-18.1) in those with AF. Compared to individuals without AF, those with AF were more likely to develop incident hip fracture in both men (unadjusted HR 2.39 [95% CI 1.96-2.91]) and women (unadjusted HR 2.91 [95% CI 2.55-3.34]). After adjusting for potential confounders, these associations were attenuated but remained statistically significant (adjusted HR 1.97 [95% CI 1.61-2.42] in men; adjusted HR 2.08 [95% CI 1.80-2.39] in women). CONCLUSIONS: A history of AF was associated with an increased risk of hip fracture in this large, population-based analysis. This association appeared to remain significant even after adjusting for potential confounders such as age, comorbidities and medication use. Patients with a history of AF may represent a clinical population in whom screening for and treatment of osteoporosis may be warranted to reduce the risk of subsequent fracture.

Effect of Loss of Heart Rate Variability on T-Wave Heterogeneity and QT Variability in Heart Failure Patients: Implications in Ventricular Arrhythmogenesis.

Heart rate variability (HRV) modulates dynamics of ventricular repolarization. A diminishing value of HRV is associated with increased vulnerability to life-threatening ventricular arrhythmias, however the causal relationship is not well-defined. We evaluated if fixed-rate atrial pacing that abolishes the effect of physiological HRV, will alter ventricular repolarization wavefronts and is relevant to ventricular arrhythmogenesis. The study was performed in 16 subjects: 8 heart failure patients with spontaneous ventricular tachycardia [HFVT], and 8 subjects with structurally normal hearts (H Norm). The T-wave heterogeneity descriptors [total cosine angle between QRS and T-wave loop vectors (TCRT, negative value corresponds to large difference in the 2 loops), T-wave morphology dispersion, T-wave loop dispersion] and QT intervals were analyzed in a beat-to-beat manner on 3-min records of 12-lead surface ECG at baseline and during atrial pacing at 80 and 100 bpm. The global T-wave heterogeneity was expressed as mean values of each of the T-wave morphology descriptors and variability in QT intervals (QTV) as standard deviation of QT intervals. Baseline T-wave morphology dispersion and QTV were higher in HFVT compared to H Norm subjects (p ≤ 0.02). While group differences in T-wave morphology dispersion and T-wave loop dispersion remained unaltered with atrial pacing, TCRT tended to fall more in HFVT patients compared to H Norm subjects (interaction p value = 0.086). Atrial pacing failed to reduce QTV in both groups, however group differences were augmented (p < 0.0001). Atrial pacing and consequent loss of HRV appears to introduce unfavorable changes in ventricular repolarization in HFVT subjects. It widens the spatial relationship between wavefronts of ventricular depolarization and repolarization. This may partly explain the concerning relation between poorer HRV and the risk of ventricular arrhythmias.

Development of Time- and Voltage-Domain Mapping (V-T-Mapping) to Localize Ventricular Tachycardia Channels During Sinus Rhythm.

BACKGROUND: In ventricular scar, impulse spread is slow because it traverses split and zigzag channels of surviving muscle. We aimed to evaluate scar electrograms to determine their local delay (activation time) and inequality in voltage splitting (entropy), and their relationship to channels. We reasoned that unlike innocuous channels, which are often short with multiple side branches, ventricular tachycardia (VT) supporting channels have very slow impulse spread and possess low entropy because of their longer protected length and relative lack of side-branching. METHODS AND RESULTS: Patients with ischemic cardiomyopathy and multiple VT were studied. In initial mapping stage (16 patients and 58 VTs), left ventricular endocardial mapping was performed in sinus rhythm. Detailed pace mapping was used to identify VT channels and confirmed, when feasible, by entrainment. Scar electrograms were analyzed in time and voltage domains to determine mean activation time, dispersion in activation time, and entropy. Predictive performances of these properties to detect VT channels were tested. In the application stage (7 patients and 20 VTs), these properties were prospectively tested to guide catheter ablation. A mean number of 763±203 sampling points were taken. From 1770 pace maps, 47 channels corresponded to VTs. A combination of scar electrograms with the latest mean activation time and minimum entropy, in a high activation dispersion region, accurately recognized regions containing VT channels (κ=0.89, sensitivity=86%, specificity=100%, positive predictive value=93%, and negative predictive value=100%). Finally, focused ablation within 5-mm rim of the prospective channel regions eliminated 18 of 20 inducible VTs. CONCLUSIONS: Activation time and entropy mapping in the scar accurately identify VT channels during sinus rhythm. The method integrates principles of reentry formation to recognize VT channels without pace mapping or mapping during VT.

Underuse and overuse of anticoagulation for atrial fibrillation: A study in Indigenous and non-Indigenous Australians.

BACKGROUND: Atrial fibrillation (AF) is a leading cause of preventable stroke in Australia. Given that anticoagulation therapy can significantly reduce this stroke risk, we sought to characterise anticoagulation use in Indigenous and non-Indigenous Australians with AF. METHODS: Administrative, clinical and prescription data from patients with AF were linked. Anticoagulation use was characterised according to guideline-recommended risk scores and Indigenous status. RESULTS: 19,613 individuals with AF were studied. Despite a greater prevalence of other risk factors, Indigenous Australians were significantly younger than their non-Indigenous counterparts (p<0.001) and thus had lower CHADS2- (1.19±0.32 vs 1.99±0.47, p<0.001) and CHA2DS2VASc-scores (1.47 ± 0.03 vs 2.82 ± 0.08, p<0.001). Correspondingly, the percentage of Indigenous Australians with CHADS2 ≥ 2 (39.6% vs 44.1%, p<0.001) and CHA2DS2VASc-scores ≥ 2 (62.9% vs 78.8%, p<0.001) was also lower. Indigenous Australians, however, had greater rates of under- and over-anticoagulation. Overall, 72.1% and 68.9% of Indigenous and non-Indigenous Australians with CHADS2 scores ≥2, and 76.3% and 71.3% with CHA2DS2VASc scores ≥2, were under-anticoagulated. Similarly, 27.4% and 24.1% of Indigenous and non-Indigenous Australians with CHADS2 scores=0, and 24.0% and 16.7% with CHA2DS2VASc-scores=0, were over-anticoagulated. In multivariate analyses, Indigenous Australians were more likely to receive under- or over-anticoagulation according to CHADS2- or CHA2DS2VASc-score (p=0.045 and p<0.001 respectively). CONCLUSION: Anticoagulation for AF is frequently not prescribed in accordance with guideline recommendations. Under-anticoagulation in those at high stroke risk, and over-anticoagulation in those at low risk, is common and more likely in Indigenous patients with AF. Improving adherence to guideline recommendations for anticoagulation in AF may reduce both ischaemic and haemorrhagic strokes in Indigenous and non-Indigenous Australians.