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Take a look at a selection of our recent media coverage:

ESC: Higher exercise capacity associated with reduced risk of atrial fibrillation

4th September 2023

Individuals with a greater exercise capacity have a reduced risk of developing atrial fibrillation (AFib), ischaemic stroke and major adverse cardiovascular events (MACE), according to the findings of a large study presented at the European Society of Cardiology (ESC) Congress, 2023.

AFib is the most common cardiac arrhythmia and has a number of different causes including auto-immune diseases such as rheumatoid arthritis.

Whether being physically fit might reduce the risk of developing AFib is unclear, although some evidence reveals a graded, inverse relationship between cardiorespiratory fitness and incident AFib, especially among obese individuals.

Exercise capacity and development of AFib

The study included 15,450 individuals without AFib who had a mean age of 54.9 years (59% male). All participants were referred for a treadmill test between 2003 and 2012.

Fitness was assessed using the Bruce protocol, where participants are asked to walk faster and at a steeper grade in successive three-minute stages. It was then calculated according to the rate of energy expenditure the participants achieved, which was expressed in metabolic equivalents (METs).

Participants were then divided into three fitness levels according to the METs achieved during the treadmill test: low (less than 8.57 METs), medium (8.57 to 10.72) and high (more than 10.72).

The researchers looked for independent associations between exercise capacity on the treadmill and the risk of new-onset AFib, risk of ischaemic stroke and MACE. The results were adjusted for potential confounders including age, sex, cholesterol level, kidney function, prior stroke, hypertension and any medications.

During the period of follow-up, new-onset AFib occurred in 3.33% of participants.

In fully adjusted models, each one MET increase in exercise treadmill testing, there was an associated 8% lower risk of AFib incidence (hazard ratio, HR = 0.92, 95% CI 0.88 – 0.97).

In addition, this one MET increase was also associated with a lower risk of ischaemic stroke (HR = 0.88, 95% CI 0.83 – 0.94) and a 14% reduced risk of MACE (HR = 0.86, 95% CI 0.84 – 0.88).

In fact, the probability of remaining free from AFib over a five-year period was calculated to be 97.1%, 98.4% and 98.4% in the low, medium and high exercise capacity groups, respectively.

Study author Dr Shih-Hsien Sung of the National Yang Ming Chiao Tung University in Taipei, Taiwan, said: ‘This was a large study with an objective measurement of fitness and more than 11 years of follow up. The findings indicate that keeping fit may help prevent atrial fibrillation and stroke.‘

Macrophage-expressed gene identified as potential target for atrial fibrillation

25th July 2023

Researchers have identified that a particular gene highly over-expressed in macrophages during atrial fibrillation (AFib) could serve as a future therapeutic target.

AFib leads to disrupted contraction of the atria, increasing the risk of both a stroke and heart failure. Now, a research study led by investigators at Massachusetts General Hospital (MGH) and published in the journal Science, shows that macrophage immune cells appear to have an important role in the development of AFib.

Their study was able to decipher how immune and stromal cells contribute to the arrhythmia. The team compared atrial tissue from patients with and without AFib and developed a mouse model of AFib which integrated hypertension, obesity and mitral valve regurgitation (HOMER) in which these cellular and transcriptomic changes were recapitulated.

Macrophage gene expression in atrial fibrillation

Using single-cell transcriptomes from human atria, researchers found inflammatory monocyte and SPP1+ macrophage expansion in atrial fibrillation. In addition, gene expression analyses showed that, in both human and mouse hearts, the SPP1 gene is highly over-expressed in macrophages during AFib. The gene produces a protein called SPP1 protein which promotes tissue scarring and is elevated in the blood of patients with AFib. In contrast, in the HOMER mice model, there were a reduced numbers of atrial macrophages when SPP1 was absent.

Through the use of cell-cell interaction analysis, it was revealed how SPP1 provided a pleiotropic signal that promoted atrial fibrillation through cross-talk with local immune and stromal cells. Moreover, the deletion of SPP1 in HOMER mice reduced AFib, which suggests that SPP1+ macrophages could serve as a target for immunotherapy in patients with atrial fibrillation.

Commenting on the research, senior author Matthias Nahrendorf from Massachusetts General Hospital, said: ‘We found that recruited macrophages support inflammation and fibrosis, or scarring, of the atria, which hinder electrical conduction between heart cells and lead to AFib. Inhibiting macrophage recruitment reduced AFib.

‘We think that this research lays the groundwork for immunomodulatory therapy of AFib, and we are currently working on several strategies to make this happen.‘

SGLT-2 inhibition lowers stroke risk in people with diabetes plus atrial fibrillation

1st June 2023

SGLT-2 inhibitor use in people with both diabetes and atrial fibrillation reduces the risk of ischaemic strokes, according to the results of a longitudinal follow‐up study.

Atrial fibrillation (AF) is the most common global cardiac arrhythmia, affecting over three million people. Having AF increases the risk of ischaemic stroke with this risk stratified by the CHA2DS2-VASc score. Fasting hyperglycaemia is a risk factor for AF although the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduces this risk.

The researchers considered whether SGLT-2 inhibitors could therefore reduce the risk of ischaemic stroke in diabetics with AF. Published in the Journal of the American Heart Association, the Taiwanese study followed a group of patients with both diabetes and AF who were prescribed either empagliflozin or dapagliflozin. These individuals were propensity matched to non-users and the incidence of ischaemic strokes documented over the next five years.

SGLT-2 inhibitor use and ischaemic stroke

A total of 6,614 patients, 801 prescribed one of the SGLT-2 inhibitors, had usable data for analysis.

After five years, 809 patients with diabetes and AF developed an ischaemic stroke. However, the rate was significantly lower among SGLT-2 inhibitor users (p = 0.021).

As expected, there was an increased risk of stroke per one-point increase CHA2DS2‐VASc score (hazard ratio, HR = 1.24, 95% CI 1.20 – 1.29, p < 0.001). Adjusting for the CHA2DS2‐VASc score lowered the stroke risk by 20% among SGLT-2 inhibitor users (HR= 0.80, 95% CI 0.64 – 0.99, p = 0.043).

The findings prompted the authors to suggest clinicians upgrade SGLT-2 inhibitors for glycaemic control, especially in those with co-existing AF.

Risk of strokes reduced by long-term statin use in atrial fibrillation

26th April 2023

The risk of strokes is significantly lower in patients with atrial fibrillation who use who use one of the statin drugs

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. Data from 2017 suggests that globally, the condition affects 3.046 million people. Furthermore, AF leads to a 5-fold increase in stroke risk with up to 30% of these due to the arrhythmia. 

In data presented at EHRA 2023, the stroke risk was lower in AF patients using statins within a year of their diagnosis. It is already known that statin use in AF reduces the risk of all-cause mortality. But whether the drugs reduce stroke risk is uncertain. However, some data suggests that high intensity statins may reduce cerebral events in patients with acute ischaemic stroke and AF.

In the study at EHRA 2023, researchers from Hong Kong, looked at a cohort of newly diagnosed AF patients. Individuals were either statin or non-statin users in relation to their AF diagnosis. For instance, a statin user was taking the drug before their AF diagnosis. The primary outcome was any form of stroke, e.g., ischaemic, systemic embolism, haemorrhagic or a transient ischaemic attack (TIA).

Risk of strokes in AF patients using statins

A total of 51,472 AF patients of whom, 11,866 were receiving a statin had analysable data.

During a median follow-up of 5.1 years, among statin users, the ischaemic stroke and systemic embolism risk was 17% lower than non-users (Hazard ratio, HR = 083, 95% CI 0.78 – 0.89). The risk of a haemorrhagic stroke (HS) was 7% lower (HR = 0.93) and the TIA risk 15% lower (HR = 0.85).

Use of statins for 6 years would reduce the risk of an ischaemic stroke or system embolism by 43% compared to use for less than 2 years (HR = 0.57). This risk was also lower for the other cerebral events.

Cardiac sphericity a possible early marker for cardiomyopathy and related adverse outcomes

6th April 2023

In a study using deep learning-enabled image segmentation of cardiac magnetic resonance imaging data, US researchers identified how variation in the left ventricle (LV) sphericity index in otherwise normal hearts, predicts the risk for cardiomyopathy and related outcomes such as atrial fibrillation.

Dilation of cardiac chambers and or a decline in systolic function are key indicators of disease and which can be assessed using conventional imaging modalities to quantify such changes. Moreover, deep neural networks have shown a great potential in image pattern recognition and automated methods achieve a performance on par with human experts in analysing cardiovascular magnetic resonance images and deriving clinically relevant measures. Cardiomyopathies of different aetiologies can often result in a similar end-stage phenotype of a more round, spherical ventricle. In fact, in patients with cardiac diseases, a greater sphericity of the left ventricle, has, for example, been shown to be an independent predictor of 10-year survival following an acute myocardial infarction. In the current study, researchers thought that even among those with normal heart function, there was likely to be variation in cardiac sphericity, in particular, sphericity of the left ventricle and that this may serve as marker of cardiac risk, especially among those with an underlying genetic risk.

Using automated deep-learning segmentation of cardiac magnetic resonance imaging (MRI) data, the researchers estimated and analysed the sphericity index in patients who were part of the UK Biobank database but excluded those with either abnormal left ventricular size or systolic function.

Cardiac sphericity and risk of cardiomyopathy

In a total of 38,897 participants, the researchers calculated that for one standard deviation increase in the sphericity index, or roundness of the heart, there was an associated 47% increased incidence of cardiomyopathy (hazard ratio, HR = 1.47, 95% CI 1.10 – 1.98, p = 0.01). In addition, the same increase in the sphericity index, was associated with a 20% increased incidence of atrial fibrillation (HR = 1.20, 95% CI 1.11 – 1.28, p < 0.001) and which was independent of clinical factors and traditional magnetic resonance imaging (MRI) measurements. In contrast, similar increases in the sphericity index were non-significantly associated with the risk of both heart failure (p = 0.3) and cardiac arrest (p = 0.70).

The team also identified four loci associated with sphericity at genome-wide significance and concluded that the variation in left ventricular sphericity in otherwise normal hearts, predicts the risk for cardiomyopathy and related outcomes and is caused by non-ischaemic cardiomyopathy.

Citation
Vukadinovic M et al. Deep learning-enabled analysis of medical images identifies cardiac sphericity as an early marker of cardiomyopathy and related outcomes. Med 2023

Augmented ablation provides no additional benefit to standard care for AF recurrence

30th March 2023

An double wide-area circumferential catheter ablation offered no added benefit to standard care in terms of atrial fibrillation recurrence

An augmented, double wide-area circumferential catheter ablation (WACA) was no better than the standard single WACA for the prevention of atrial fibrillation (AF) recurrence in patients with paroxysmal AF, according to a randomised trial by Canadian researchers.

The proportion of patients affected by AF varies with age, is slightly more common in men and according to one European study, the prevalence ranged from 0.12 – 0.16% in those under 49 years of age to between 10 and 17% in those 80 years and older. While anti-arrhythmic drugs are effective, among patients with paroxysmal AF who have not tried such drugs, radio-frequency ablation results in a lower rate of recurrent atrial tachyarrhythmias after 2 years. Ectopic beats from the pulmonary veins (PV) often trigger AF and hence catheter ablation approaches have focused on PV isolation (PVI). However, PV electrical reconnection is frequently detected in subjects experiencing recurrent arrhythmia and relatively common, affecting affecting 58% of AF-free patients. Given this high level of AF recurrence, in the current study, the Canadian team wondered if an augmented double wide-area circumferential ablation, i.e., that included a wider area of atrial ablation, might be more effective than the standard, single WACA.

The researchers randomised patients 18 years and older with symptomatic paroxysmal AF, in a 1:1 fashion, to receive radio-frequency catheter ablation for pulmonary vein isolation with either a standard single WACA or an augmented double WACA. The primary outcome was atrial tachyarrhythmia (including atrial tachycardia, atrial flutter, or AF, lasting longer than 30 seconds) recurrence between 91 and 365 days post-ablation.

Augmented vs standard ablation outcomes

A total of 398 patients with a mean age of 61 years (32.9% female) were randomised to the single WACA or control arm (195) or the double WACA arm (203).

In total, 26.7% in the single WACA arm and 24.6% in the double WACA arm had recurrent AA at 1 year (relative risk, RR = 0.92 95% CI 0.66 – 1.29, p = 0.64). Furthermore, a similar proportion in both arms (10.3% vs 7.4%, single vs double WACA) underwent repeated catheter ablation (RR = 0.72, 95% CI 0.38 – 1.36).

There were also no differences in the level of serious adverse events (6.7% vs 6.9%, single vs double WACA).

The authors concluded that additional ablation by performing a double ablation lesion set did not result in improved freedom from recurrent AA compared with a standard single ablation set.

Citation
Nair GM et al. Standard vs Augmented Ablation of Paroxysmal Atrial Fibrillation for Reduction of Atrial Fibrillation Recurrence: The AWARE Randomized Clinical Trial. JAMA Cardiol 2023

Several autoimmune diseases associated with increased risk of atrial fibrillation

18th February 2023

Having autoimmune diseases (AIDs) seems to increase the risk of developing atrial fibrillation according to the findings of a prospective study by Dutch researchers.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and data from 2017 suggests that globally, there were 3.046 million new cases. Although the underlying cause of AF remains uncertain, there is a suggestion of a mechanistic link with inflammatory processes. Moreover, a feature of autoimmune diseases such as rheumatoid arthritis is inflammation and one meta-analysis found a 29% higher risk of AF among those with rheumatoid arthritis. Nevertheless, the link between AF and other autoimmune disorders is less clear. As a result, in the current study, the Dutch team turned to data held in the UK Biobank and looked for those diagnosed rheumatic fever, gastrointestinal AIDs and other AIDs e.g. those affecting the musculoskeletal, connective tissues and neurological systems. Such individuals were monitored over time for the development of AF. In addition, the team collected data on cardiovascular risk factors such as hypertension, type 2 diabetes, body mass index etc and which were adjusted for in regression models.

Autoimmune diseases and development of atrial fibrillation

A total of 494,072 individuals with a median age of 58 (54.8% female) were followed for a median of 12.8 years and during this time 5.5% of the cohort developed AF.

In fully adjusted models, among those with rheumatic fever but no cardiac involvement, there was a 47% higher risk of developing AF (hazard ratio, HR = 1.47, 95% CI 1.26 – 1.72). Similarly, there were elevated risks for those with several autoimmune diseases including Crohn’s disease (HR = 1.23), ulcerative colitis (HR = 1.17), rheumatoid arthritis (HR = 1.39) systemic lupus erythematosus (HR = 1.82) and systemic sclerosis (HR = 2.32).

When analysed by gender, the researchers found that for many of these disorders, there was a higher risk among women although the risk was higher among men but only for ulcerative colitis.

The authors concluded that whilst their data showed how autoimmune diseases were associated with the development of AF, further evidence was need to support the clinical translation of these findings.

Citation
Tilly MJ et al. Autoimmune diseases and new-onset atrial fibrillation: a UK Biobank study. Eurospace 2022 (Online ahead of print)

Catheter ablation delays worsen outcomes for patients with atrial fibrillation

3rd February 2023

Catheter ablation delays for atrial fibrillation leads to a worsening of adverse cardiac outcomes in patients with and without heart failure

Delaying the use of catheter ablation for those with atrial fibrillation (AF) and or heart heart failure, leads to worse cardiovascular outcomes such as mortality, stroke and AF recurrence according to an analysis by US researchers.

AF is the most clinically significant arrhythmia in practice, affecting between 1 and 3% of the population though this rises to 17% in those 80 years of age and older. AF often co-exists with heart failure and the presence of both conditions, exerts a major detrimental effect on patient’s cardiovascular health and overall wellbeing. Atrial fibrillation can be managed medically with anti-arrhythmic drugs although catheter ablation therapy is also an option. However, a recent study has indicated that among AF patients with stable heart failure, the use of catheter ablation was superior, with respect to survival, freedom from AF recurrence and quality of when compared to drug treatment. With clearly beneficial effects from ablation therapy, one unanswered question is when the ablation should be undertaken in relation to the AF diagnosis. In other words, might delaying catheter ablation, affect the subsequent risk of death or other outcomes such as hospitalisation for heart failure. In a 2013 study, researchers found that delaying ablation worsened the success of the procedure. Moreover, does the impact of any delay affect patients with differing levels of heart failure, based on the extent of left ventricular dysfunction? This was the subject of the current study by the US team.

Researchers studied patients with at least 12 months follow-up data following their ablation procedure and who were then stratified based on their ejection fraction as either < 35% or > 35%. The team then compared several adverse outcomes such as mortality, heart failure (HF) hospitalisation and AF recurrence in relation to the delay between the initial AF diagnosis and the time of ablation. These delays were categorised as 30 – 180 days, 181 – 454 days, 546 – 1825 days or > 1825 days.

Catheter ablation delay and adverse outcomes

Data were available for 9,979 patients with the overall time delay between diagnosis and the first ablation being a median of 2 years and this figure was not significantly different between the two categories of ejection fraction (p = 0.66).

When considering patients with an ejection fraction > 35%, a delay of 181 – 545 days (compared to 30 – 180 days) was associated with a significantly higher mortality risk (hazard ratio, HR = 2.02 (95% CI 1.38 – 2.96) and this risk was more than double, among those waiting longer than 1825 days (HR = 4.39). In addition, there were elevated risks for HF hospitalisations and AF recurrence incurred by delaying ablation therapy.

Among those with an ejection fraction < 35%, there were also elevated risks of mortality, HF hospitalisation and AF recurrence associated with ablation delays, e.g. HR = 3.77 for mortality.

The authors concluded that catheter ablation delays among those with AF increased the risks for adverse events in patients either with or without structural heart disease, highlighting the need for earlier ablation therapy.

Citation
Sessions AJ et al. Increasing time between first diagnosis of atrial fibrillation and catheter ablation adversely affects long-term outcomes in patients with and without structural heart disease. J Cardiovasc Electrophysiol 2023

ECG and radiomics model enhance detection of AF in women

18th November 2022

An ECG and radiomics model derived from cardiovascular magnetic resonance imaging improved the detection of atrial fibrillation in women

A model combining features of an ECG and radiomics data derived from cardiovascular magnetic resonance imaging improved the detection of atrial fibrillation (AF) in women to a greater extent than either model alone according to the findings of a study by Spanish and UK researchers.

Atrial fibrillation is the most common cardiac arrhythmia, characterised by an irregular heart rhythm and an often abnormally rapid heart rate and globally has been estimated to affect 0.51% of the population. AF is diagnosed from an ECG in which typically, P-waves are absent and there is both a chaotic baseline and an irregular ventricular rate. Cardiac magnetic resonance (CMR) is the reference imaging modality for assessment of cardiac structure and function and CMR radiomics has the potential to improve diagnostic accuracy. Moreover, Cardiac MRI of the atrial substrate is not only a tool for management and treatment of arrhythmia, but also to individualise the prevention of stroke and major cardiovascular events. But what remains unclear is whether the use of a CMR-based radiomics model can identify patients with AF and more importantly, if addition of a model that uses ECG-derived data, would further enhance the potential to detect AF.

In the present study, researchers examined the feasibility of combining a CMR-derived radiomics model and one based on ECG data. The team used information from the UK Biobank and identified patients who had both an ECG and CMR scan and compared their findings with healthy controls. Models were assessed using the area under the receiver operating characteristics curve (AUC) and associated sensitivity and specificity.

ECG and radiomics model and atrial fibrillation detection

A total of 32,121 participants with a mean age of 63 years (51% female) were included and of whom, 495 (63% male) had AF.

Overall, the AUC for the combined model was similar to the ECG-model (0.87 vs 0.86), i.e., adding the radiomics model did not significantly improve predictive power. In fact, when comparing the predictive power of models between the sexes, the AUC for the ECG-model was less predictive for women than men (0.77 vs 0.88, p < 0.05). However, although accuracy improved for women when combined with the CMR-model, but this only improved to the level of the ECG-model for men (0.87 vs 0.88, women vs men). Finally, when considering AF patients who had a normal ECG, the combined model had an AUC of 0.61.

The authors concluded that their integrative radiomics-ECG model presents a potential novel approach for earlier detection of AF.

Citation
Pujadas ER et al. Atrial fibrillation prediction by combining ECG markers and CMR radiomics. Sci Rep 2022

Misuse of illicit substances linked to higher risk of atrial fibrillation

2nd November 2022

Misuse of illicit substances such as methamphetamines, cocaine, opiates and cannabis are linked to an increased risk of atrial fibrillation

The misuse of the illicit substances methamphetamine, cocaine, opiates and cannabis has been found to increase the risk of incident atrial fibrillation (AF) according to the findings of a longitudinal analysis by Californian researchers.

Atrial fibrillation is the most frequent cardiac arrhythmia, and it has been estimated that 6 -12 million people worldwide suffer from the condition. Moreover, the presence of the arrhythmia is also independently associated with a higher risk of all-cause mortality. While it has become well established that a higher intake of alcohol as well as smoking, increases the risk of AF, the relationship with the misuse of illicit drugs is less clear. Whereas prior work has suggested that methamphetamine abuse leads to ECG changes that pose a higher risk for ventricular arrhythmias and most notably torsades de pointes, less is known about the effect on AF. However, there is some data linking an increased risk of AF from use of both cannabis and cocaine though these findings are derived from case studies. But in contrast, one study actually identified how cannabis use was associated with a lower odds of AF.

In the present study, the US researchers sought to determine whether misuse of the illicit substances, methamphetamine, cocaine, opiates and cannabis were a predictor of incident AF. The team used several California healthcare databases, e.g., emergency department and inpatient to capture repeat visits for a given patient. They extracted demographic and co-morbidity data and excluded those with known AF and looked at cases where substance use was considered present at the first healthcare encounter. The researchers then compared the baseline and clinical characteristics of patients for each of the different drugs and examined the association with AF, adjusting for covariates known to be associated with AF.

Illicit substance misuse and incident atrial fibrillation

In a total of 23,561,884 individuals, 98,271 used methamphetamine, 48,701 cocaine, 10,032 opiates and 132,834 cannabis. From this total, 4.2% developed incident AF during the period of study from 2005 to 2015. The mean age of participants ranged from 32.3 years (cannabis) to 41.1 (cocaine) and the proportion of females from 28.3% to 55%.

After adjustment for covariates, methamphetamine use was associated with an 86% higher risk of developing incident AF (Hazard ratio, HR = 1.86, 95% CI 1.81 – 1.92). Similar and significantly elevated risks were seen for cocaine (HR = 1.61), opiates (HR = 1.74) and cannabis (HR = 1.35). Interesting, polysubstance use was also associated with a higher risk of AF compared to single drug misuse (HR = 1.63, 95% CI 1.61 – 1.66).

The authors concluded that for each of the misused substances analysed, there was a higher risk of developing incident AF after controlling for conventional AF risk factors.

Citation
Lin AL et al. Cannabis, cocaine, methamphetamine, and opiates increase the risk of incident atrial fibrillation. Eur Heart J 2022

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