Digitally enabled acute care for atrial fibrillation: conception, feasibility and early outcomes of an AF virtual ward.

BACKGROUND: Atrial fibrillation (AF) represents a growing healthcare challenge, mainly driven by acute hospitalisations. Virtual wards could be the way forward to manage acute AF patients through remote monitoring, especially with the rise in global access to digital telecommunication and the growing acceptance of telemedicine post-COVID-19. METHODS: An AF virtual ward was implemented as a proof-of-concept care model. Patients presenting acutely with AF or atrial flutter and rapid ventricular response to the hospital were onboarded to the virtual ward and managed at home through remote ECG-monitoring and 'virtual' ward rounds, after being given access to a single-lead ECG device, a blood pressure monitor and pulse oximeter with instructions to record daily ECGs, blood pressure, oxygen saturations and to complete an online AF symptom questionnaire. Data were uploaded to a digital platform for daily review by the clinical team. Primary outcomes included admission avoidance, readmission avoidance and patient satisfaction. Safety outcomes included unplanned discharge from the virtual ward, cardiovascular mortality and all-cause mortality. RESULTS: There were 50 admissions to the virtual ward between January and August 2022. Twenty-four of them avoided initial hospital admission as patients were directly enrolled to the virtual ward from outpatient settings. A further 25 readmissions were appropriately prevented during virtual surveillance. Patient satisfaction questionnaires yielded 100% positive responses among participants. There were three unplanned discharges from the virtual ward requiring hospitalisation. Mean heart rate on admission to the virtual ward and discharge was 122±26 and 82±27 bpm respectively. A rhythm control strategy was pursued in 82% (n=41) and 20% (n=10) required 3 or more remote pharmacological interventions. CONCLUSION: This is a first real-world experience of an AF virtual ward that heralds a potential means for reducing AF hospitalisations and the associated financial burden, without compromising on patients' care or safety.

The AFLETES Study: Atrial Fibrillation in Veteran Athletes and the Risk of Stroke.

OBJECTIVES: Endurance athletes are at an increased risk of atrial fibrillation (AF) when compared with the general population. However, the risk of stroke in athletes with AF is unknown. DESIGN AND SETTING: We aimed to assess this risk using an international online survey. PATIENTS: Individuals that had competed in ≥1 competitive events and were ≥40 years old were included. INTERVENTIONS: Self-reported demographic, medical history, and training history data were collected, and a CHA 2 DS 2 -VASc was calculated. MAIN OUTCOME MEASURES: Binary logistic regression was used to assess variables associated with AF and stroke. RESULTS: There were 1002 responses from participants in 41 countries across Africa, Asia, Australasia, Europe, and North and South America, and 942 were included in the final analysis. The average age was 52.4 ± 8.5 years, and 84% were male. The most common sports were cycling (n = 677, 72%), running (n = 558, 59%), and triathlon (n = 245, 26%). There were 190 (20%) individuals who reported AF and 26 individuals (3%) who reported stroke; of which, 14 (54%) had AF. Lifetime exercise dose [odds ratio (OR), 1.02, 95% confidence interval (95% CI),1.00-1.03, P = 0.02] and swimming (OR, 1.56, 95% CI, 1.02-2.39, P = 0.04) were associated with AF in multivariable analysis, independent of other risk factors. Atrial fibrillation was associated with stroke (OR, 4.18, 95% CI, 1.80-9.72, P < 0.01), even in individuals with a low (0/1) CHA 2 DS 2 -VASc score (OR, 4.20, 95% CI, 1.83-9.66, P < 0.01). CONCLUSIONS: This survey provides early evidence that veteran endurance athletes who develop AF may be at an increased risk of developing stroke, even in those deemed to be at low risk by CHA 2 DS 2 -VASc score.

The Influence of Environmental Air Pollution on Ventricular Arrhythmias: A Scoping Review.

INTRODUCTION: Exposure to air pollution is a recognised risk factor for cardiovascular disease and has been associated with supraventricular arrhythmias. The effect of air pollution on ventricular arrhythmias is less clear. This scoping review assessed the effects of particulate and gaseous air pollutants on the incidence of ventricular arrhythmias. METHODS: MEDLINE and EMBASE databases were searched for studies assessing the effects of air pollutants on ventricular tachycardia and ventricular fibrillation. These pollutants were particulate matter (PM) 2.5, PM10, Nitrogen Dioxide (NO2), Carbon Monoxide (CO), Sulphur Dioxide (SO2), and Ozone (O3). RESULTS: This review identified 27 studies: nine in individuals with implantable cardioverter defibrillators, five in those with ischaemic heart disease, and 13 in the general population. Those with ischaemic heart disease appear to have the strongest association with ventricular arrhythmias in both gaseous and particulate pollution, with all three studies assessing the effects of PM2.5 demonstrating some association with ventricular arrythmia. Results in the general and ICD population were less consistent. CONCLUSION: Individuals with ischaemic heart disease may be at an increased risk of ventricular arrhythmias following exposure to air pollution.

Simultaneous Whole-Chamber Non-contact Mapping of Highest Dominant Frequency Sites During Persistent Atrial Fibrillation: A Prospective Ablation Study.

Purpose: Sites of highest dominant frequency (HDF) are implicated by many proposed mechanisms underlying persistent atrial fibrillation (persAF). We hypothesized that prospectively identifying and ablating dynamic left atrial HDF sites would favorably impact the electrophysiological substrate of persAF. We aim to assess the feasibility of prospectively identifying HDF sites by global simultaneous left atrial mapping. Methods: PersAF patients with no prior ablation history underwent global simultaneous left atrial non-contact mapping. 30 s of electrograms recorded during AF were exported into a bespoke MATLAB interface to identify HDF regions, which were then targeted for ablation, prior to pulmonary vein isolation. Following ablation of each region, change in AF cycle length (AFCL) was documented (≥ 10 ms considered significant). Baseline isopotential maps of ablated regions were retrospectively analyzed looking for rotors and focal activation or extinction events. Results: A total of 51 HDF regions were identified and ablated in 10 patients (median DF 5.8Hz, range 4.4-7.1Hz). An increase in AFCL of was seen in 20 of the 51 regions (39%), including AF termination in 4 patients. 5 out of 10 patients (including the 4 patients where AF termination occurred with HDF-guided ablation) were free from AF recurrence at 1 year. The proportion of HDF occurrences in an ablated region was not associated with change in AFCL (τ = 0.11, p = 0.24). Regions where AFCL decreased by 10 ms or more (i.e., AF disorganization) after ablation also showed lowest baseline spectral organization (p < 0.033 for any comparison). Considering all ablated regions, the average proportion of HDF events which were also HRI events was 8.0 ± 13%. Focal activations predominated (537/1253 events) in the ablated regions on isopotential maps, were modestly associated with the proportion of HDF occurrences represented by the ablated region (Kendall's τ = 0.40, p < 0.0001), and very strongly associated with focal extinction events (τ = 0.79, p < 0.0001). Rotors were rare (4/1253 events). Conclusion: Targeting dynamic HDF sites is feasible and can be efficacious, but lacks specificity in identifying relevant human persAF substrate. Spectral organization may have an adjunctive role in preventing unnecessary substrate ablation. Dynamic HDF sites are not associated with observable rotational activity on isopotential mapping, but epi-endocardial breakthroughs could be contributory.

An algorithm to assist novices with electrocardiogram interpretation: Validation with the Delphi Method.

PURPOSE: Electrocardiograms (ECG) are often poorly interpreted by novices and this can delay time-sensitive, critical intervention. This study aimed to assess, improve and validate a stepwise ECG algorithm designed to assist with ECG interpretation by novices by soliciting the opinions of an international cohort of expert cardiologists. METHODS: The Delphi Method was used, and an online questionnaire was sent to an international panel of cardiologists. Experts were required to evaluate each step of the algorithm and offer comments. Feedback was analysed by the investigators, changes to the algorithm were made and these were sent back to the experts until a consensus was reached. Two rounds of the Delphi Method were required to achieve consensus. RESULTS: Overall, 55 responses were achieved (round one = 33, round two = 22). The average agreement in round one was 90.2% with 25 changes from 124 comments. Round two achieved 93.4% agreement with 12 changes from 57 comments. The threshold for consensus was set at 90% and was confirmed as being reached by all four investigators of this study. A final algorithm was therefore established. The ECG algorithm was validated through a rigorous two-stage development and review process. CONCLUSIONS: The algorithm was validated as a safe, informative tool for novices to use to improve ECG interpretation. Real-world user validation is now required to further improve the algorithm.

Palpitation referrals from primary care to a secondary care cardiology outpatient clinic: assessing adherence to guidelines.

BACKGROUND AND AIMS: Palpitations are a common presentation in primary care. Guidelines have been developed to identify patients with palpitations who require further assessment by a cardiologist in secondary care. However, patients that do not meet guideline thresholds for referrals are still referred to secondary care services. This audit evaluated the adherence to referral guidelines at our trust and assessed the characteristics of patients who were referred appropriately versus those referred without meeting guideline referral thresholds (inappropriate referral). RESULTS: Palpitation referrals to a single cardiology outpatient clinic were assessed (n = 66). Half the patients referred for palpitations were referred inappropriately (n = 34, 51.5%). Patients referred inappropriately were more likely to have a benign diagnosis after assessment (91.2%). These patients also had significantly fewer investigations [mean difference of 1.1 (confidence interval: 0.6-1.6)]. Specialist investigations, such as cardiac event recorders (P < 0.05) and cardiac magnetic resonance imaging (P < 0.05) were less likely to be used in inappropriately referred patients. CONCLUSIONS: The results from this audit provide early evidence that there are a significant number of patients who are being referred that could be managed in primary care. Further studies are needed to confirm our findings in larger cohorts and to establish the underlying reasons for inappropriate referrals.

ß1-Adrenoreceptor Polymorphisms and Blood Pressure: 49S Variant Increases Plasma Renin But Not Blood Pressure in Hypertensive Patients.

BACKGROUND: Activation of beta-1 adrenoreceptor (ß1-AR) in the kidney releases renin that plays a major role in the maintenance of blood pressure. Genetic variation in ß1-AR could therefore alter the physiological and clinical effects of this hormone. We tested this hypothesis in patients from a primary care cohort being screened for primary hyperaldosteronism (n = 467). METHODS: Demographic and hemodynamic data were measured and plasma renin was determined by a standard immunoassay. Subjects were genotyped for the 2 common single-nucleotide polymorphisms Arg389Gly (rs1801253) and Ser49Gly (rs1801252), and thus the 4 possible haplotypes in ß1-AR gene. RESULTS: In patients being screened for hyperaldosteronism, plasma renin was significantly elevated in Ser49 homozygotes (49SS) compared with Gly49 (49G) allele carriers (0.307 ± 0.03 vs. 0.164 ± 0.05; P = 0.01). However, this did not translate into differences in either blood pressure or heart rate. On the other hand, the Arg389Gly polymorphism did not affect either plasma renin or blood pressure in this group. There was also no evidence that the 2 loci were linked in this group of patients. CONCLUSION: These data suggest that in this cohort the Ser49 variant of the Ser49Gly ß1-AR gene polymorphism associates with higher renin levels. However, these common ß1-AR gene polymorphisms do not affect blood pressure in the same cohort.

Prospective evaluation of two novel ECG-based restitution biomarkers for prediction of sudden cardiac death risk in ischaemic cardiomyopathy.

OBJECTIVE: To improve prediction of sudden cardiac death (SCD) in patients with ischaemic cardiomyopathy (ICM). Electrical heterogeneity is known to contribute to risk of SCD. We have previously developed Regional Restitution Instability Index (R2I2), an ECG-based biomarker, which quantifies cardiac electrical instability by measuring heterogeneity in electrical restitution, and demonstrated its potential utility for risk stratification in a retrospective analysis of patients with ICM. Here, we examined R2I2 in a prospective ICM cohort and also tested the predictive value of another ECG-based biomarker, Peak ECG Restitution Slope (PERS). METHODS: Prospective, blinded, observational study of 60 patients with ICM undergoing implantable cardioverter defibrillator risk stratification. R2I2 was calculated from an electrophysiological study (EPS) using ECG surrogates for action potential duration and diastolic interval. R2I2 quantifies inter-lead electrical restitution heterogeneity. PERS was the peak restitution curve slope taken as a mean across the 12 ECG leads. Endpoints were ventricular arrhythmia (VA)/SCD. RESULTS: Over median follow-up of 22 months, 16 (26.6%) patients achieved endpoint. R2I2 was significantly higher in these patients compared with those without an event (mean ± SEM: 1.11 ± 0.09 vs 0.84 ± 0.04, p=0.003) as was PERS (median(IQR): 1.35(0.60) vs 1.08(0.52), p=0.014). R2I2≥1.03, the cut-off used in our previous study, identified patients with a significantly higher risk of VA/SCD independent of EPS result, LVEF or QRS duration with a relative risk of 6.5 (p=0.008). Patients positive for R2I2 and PERS had a relative risk of VA/SCD 21.6 times that of those negative for R2I2 and PERS (p<0.0001). CONCLUSIONS: R2I2 and PERS each independently and in combination, identify patients with ICM that are at high risk of developing ventricular arrhythmias (VA). R2I2/PERS represent promising risk markers for SCD discrimination. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01944514.

The impact of power output during percutaneous catheter radiofrequency ablation for atrial fibrillation on efficacy and safety outcomes: a systematic review.

INTRODUCTION: Percutaneous catheter radiofrequency ablation (RFA) has been widely used to treat patients with atrial fibrillation (AF). Success rates are, however, variable and optimal levels of power used and duration of power delivery have not been fully established. Different ablation centers continue to use various power protocols. We undertook a comprehensive systematic review to evaluate the impact of power output during RFA for AF on efficacy and safety. METHODS AND RESULTS: We systematically searched MEDLINE and Cochrane Central Register of Controlled Trials databases for studies on power output during percutaneous RFA for AF. The marked heterogeneous nature of the studies prohibited a meta-analysis. The main findings were (1) power output of ≤30 watts (W) has good safety profiles but low efficacy rates; (2) power output of >30 W-<45 W is safe with good efficacy; (3) power output of ≥ 45 W has a better efficacy profile but associated with a high risk of complications; (4) delivery of higher power of ≥ 45 W at shorter duration (15-20 seconds) is safe and efficacious; and (5) energy titration with visualization of microbubbles by intracardiac echocardiography (ICE) has better efficacy and safety profiles compared to RFA without ICE. CONCLUSIONS: Despite the overall reduced quality data relating power to outcomes of RFA for AF, the optimal power output showing good efficacy and safety profiles appears generically to be >30 W-<45 W, with significant variation in the literature.

A novel surface electrocardiogram-based marker of ventricular arrhythmia risk in patients with ischemic cardiomyopathy.

BACKGROUND: Better sudden cardiac death risk markers are needed in ischemic cardiomyopathy (ICM). Increased heterogeneity of electrical restitution is an important mechanism underlying the risk of ventricular arrhythmia (VA). Our aim was to develop and test a novel quantitative surface electrocardiogram-based measure of VA risk in patients with ICM: the Regional Restitution Instability Index (R2I2). METHODS AND RESULTS: R2I2, the mean of the standard deviation of residuals from the mean gradient for each ECG lead at a range of diastolic intervals, was measured retrospectively from high-resolution 12-lead ECGs recorded during an electrophysiology study. Patient groups were as follows: Study group, 26 patients with ICM being assessed for implantable defibrillator; Control group, 29 patients with supraventricular tachycardia undergoing electrophysiology study; and Replication group, 40 further patients with ICM. R2I2 was significantly higher in the Study patients than in Controls (mean ± standard error of the mean: 1.09±0.06 versus 0.63±0.04, P<0.001). Over a median follow-up period of 23 months, 6 of 26 Study group patients had VA or death. R2I2 predicted VA or death independently of demographic factors, electrophysiology study result, left ventricular ejection fraction, or QRS duration (Cox model, P=0.029). R2I2 correlated with peri-infarct zone as assessed by cardiac magnetic resonance imaging (r=0.51, P=0.024). The findings were replicated in the Replication group: R2I2 was significantly higher in 11 of 40 Replication patients experiencing VA (1.18±0.10 versus 0.92±0.05, P=0.019). In combined analysis of ICM cohorts, R2I2 ≥1.03 identified subjects with significantly higher risk of VA or death (43%) compared with R2I2 <1.03 (11%) (P=0.004). CONCLUSIONS: In this pilot study, we have developed a novel VA risk marker, R2I2, and have shown that it correlated with a structural measure of arrhythmic risk and predicted risk of VA or death in patients with ICM. R2I2 may improve risk stratification and merits further evaluation. (J Am Heart Assoc. 2012;1:e001552 doi: 10.1161/JAHA.112.001552.).

Functional result following direct coronary artery stenting with drug eluting stents in chronic stable angina is similar to stenting after balloon predilatation.

BACKGROUND: The safety and efficacy of direct coronary artery stenting without predilatation using drug eluting stents has not been firmly established. Concerns have been raised that this technique may be associated with increased risk of immediate and short term complications. METHODS: 68 consecutive patients with chronic stable angina and angiographically proven single vessel disease were randomised to undergo either direct coronary artery stenting or stenting after balloon predilation. All patients underwent Pressure Wire directed percutaneous coronary intervention (PCI) and drug eluting stents were deployed. Pre and post-PCI fractional flow reserve (FFR) was assessed following administration of intravenous adenosine. Post-procedure troponin I (TNI) and creatine kinase-MB (CK-MB) were compared. 51 of the 68 patients successfully completed a 6 month treadmill exercise test. RESULTS: There were no significant differences in the demographic, risk factor or angiographic profiles between the two groups except for hyperlipedemia and statin therapy. Drug eluting stents were deployed in all patients. Majority of the lesions were relatively simple (all lesions were either type A or B1). The pre-procedure FFR [mean(SD)]was marginally lower in the pre-dilatation group compared to the direct stenting group [0.57(0.17) versus 0.64(018); p=0.04]. The post-procedure FFR was similar in both groups [0.97(0.05) versus 0.98(0.03); p=0.26]. There was no difference in the post-procedure rise of either TNI or CK-MB in both groups. At 6 months, no major adverse cardiac events (death, MI or revascularisation) were observed in all patients. A positive exercise test was seen in 5 patients (10%) and there was no difference between the two groups. CONCLUSION: A strategy of direct stenting of appropriate coronary lesions with drug eluting stents in patients with chronic stable angina is associated with similar functional results as balloon predilatation followed by stenting.

Functional responses of human beta1 adrenoceptors with defined haplotypes for the common 389R>G and 49S>G polymorphisms.

OBJECTIVES: The human beta1-adrenoceptor (beta1-AR) is an important therapeutic target for cardiovascular diseases and has two common functional polymorphisms (49S>G and 389R>G). These polymorphisms have only been studied in isolation, however, and not in the context of the four haplotypes (SR, SG, GR and GG) that exist in native beta1-ARs. METHODS: To address this, the function of each of the receptor haplotypes was studied in HEK 293 cells stably transfected with appropriately modified human beta1-adrenoceptor cDNA sequence. RESULTS: The affinity for the beta-adrenoceptor ligand, [125I]-cyanopindolol, was not significantly different across the haplotypes, but a high affinity state for the beta1-AR could only be demonstrated for receptors carrying the 389R substitution. Both basal (GR 36.3 +/- 2.9* vs. SR 16.5 0 +/- 3.6 and GG 31.7 +/- 1.4* vs. SG 15.6 +/- 1.5 pmol/mg protein; *P < 0.001) and maximal (GR 163 +/- 7.6 vs. SR 124 +/- 8.1* and GG 75.0 +/- 1.0 vs. SG 52.4 +/- 1.1* pmol/mg protein; *P < 0.001) isoprenaline-evoked cAMP production was significantly affected by both substitutions. Incubation with isoprenaline (10 microm for 30 min or 20 h) caused increased down-regulation of beta1-ARs in cells expressing GG and GR haplotypes (at 20 h percentage fall respectively -28.1 +/- 5.2 and -38.2 +/- 3.0). CONCLUSIONS: These data highlight important functional differences between the common beta1-AR haplotypes and the need for consideration of haplotypes and not individual genotypes in determining the in-vivo role of these polymorphisms within this important drug target.