South Asian ethnicity is associated with a lower prevalence of atrial fibrillation despite greater prevalence of established risk factors: a population-based study in Bradford Metropolitan District

Aims: Previous studies indicate that South Asians (SAs) may have a reduced risk of developing atrial fibrillation (AF) despite having a higher prevalence of traditional cardiovascular risk factors. This observational study was designed to explore the relative differences between SAs and Whites in a well-defined, multi-ethnic population with careful consideration of traditional cardiovascular risk factors that are thought to contribute to the development of AF. Methods and results: Anonymized data from 417 575 adults were sourced from primary care records within Bradford Metropolitan District, UK. Atrial fibrillation diagnosis was indicated by the presence on the AF Quality Outcomes Framework register. Self-reported ethnicity was mapped to census ethnic codes. The age-standardized prevalence rates of AF were calculated for comparison between the White and SA populations; our study sample presented relative proportions of 2.39 and 0.4%. Multivariable logistic regression analysis was performed to estimate the odds of developing AF given SA ethnicity. Adjustment for age, sex, and established risk factors found a 71% reduction in odds of AF in SAs when compared with Whites [odds ratio (OR): 0.29, 95% confidence interval (CI): 0.26–0.32]. When stratified by ethnicity, analyses revealed significantly different odds of AF for patients with diabetes; diabetes was not associated with the development of AF in the SA population (0.81, 95% CI: 0.63–1.05). Conclusion: This study, in a multi-ethnic population, presents ethnicity as a predictor of AF in which prevalence is significantly lower in SAs when compared with Whites. This is despite SAs having a higher frequency of established risk factors for the development of AF, such as ischaemic heart disease, heart failure, hypertension, and type 2 diabetes. These findings are consistent with previous literature and add weight to the need for further investigation, although this is the first study to investigate the differential associations of individual risk factors with development of AF

Phase entrainment of induced ventricular fibrillation: A human feasibility and proof of concept study

Cardioversion and defibrillation by a single high energy shock applied by myocardial or body surface electrodes is painful, causes long term tissue damage, and is associated with worsening long term outcomes, but is almost always required for treatment of ventricular fibrillation . As a initial step towards developing methods that can terminate ventricular arrhythmias painlessly, we aim to determine if pacing stimuli at a rate of 5/s applied via an implantable cardiac defibrillator (ICD) can modify human ventricular fibrillation. In 8 patients undergoing defibrillation testing of a new/exchanged intracardiac defibrillator, five seconds of pacing at five stimuli per second was applied during the 10-20 seconds of induced ventricular fibrillation before the defibrillation shock was automatically applied, and the cardiac electrograms recorded and analyzed. The high frequency pacing did not entrain the ventricular fibrillation, but altered the dominant frequency in all 8 patients, and modulated the phase computed via the Hilbert Transform, in four of the patients. In this pilot study we demonstrate that high frequency pacing applied via ICD electrodes during VF can alter the dominant frequency and modulate the probability density of the phase of the electrogram of the ventricular fibrillation

Imaging, biomarker and invasive assessment of diffuse left ventricular myocardial fibrosis in atrial fibrillation

Background Using cardiovascular magnetic resonance imaging (CMR), it is possible to detect diffuse fibrosis of the left ventricle (LV) in patients with atrial fibrillation (AF), which may be independently associated with recurrence of AF after ablation. By conducting CMR, clinical, electrophysiology and biomarker assessment we planned to investigate LV myocardial fibrosis in patients undergoing AF ablation. Methods LV fibrosis was assessed by T1 mapping in 31 patients undergoing percutaneous ablation for AF. Galectin-3, coronary sinus type I collagen C terminal telopeptide (ICTP), and type III procollagen N terminal peptide were measured with ELISA. Comparison was made between groups above and below the median for LV extracellular volume fraction (ECV), followed by regression analysis. Results On linear regression analysis LV ECV had significant associations with invasive left atrial pressure (Beta 0.49, P = 0.008) and coronary sinus ICTP (Beta 0.75, P < 0.001), which remained significant on multivariable regression. Conclusion LV fibrosis in patients with AF is associated with left atrial pressure and invasively measured levels of ICTP turnover biomarker

P wave indices, heart rate variability and anthropometry in a healthy South Asian population

Background: South Asians have a low prevalence of atrial fibrillation (AF) in comparison with White Europeans despite a higher burden of hypertension, diabetes mellitus and coronary artery disease. The reason for this disparity is unclear but may relate to electrophysiological or structural differences within the atria or variations in autonomic function. We aimed to assess these areas using a range of non-invasive cardiac investigations. Methods: A prospective cohort study was performed on 200 South Asian and 200 Caucasian healthy volunteers aged 18–40 years. All subjects underwent electrocardiography (ECG), echocardiography and anthropometric measurements. Eighty subjects in each cohort underwent 24 hour ambulatory ECG and fifty subjects in each cohort underwent exercise testing. Results: Compared with White Europeans, South Asians were of a smaller height with lower lean body mass and smaller left atrial size. They had reduced P wave dispersion and P wave terminal force in lead V1. South Asians had a lower burden of supraventricular ectopy. They had a higher mean heart rate and South Asian males had lower heart rate variability, suggestive of sympathetic predominance. Exercise capacity was lower in South Asians. Conclusions: South Asians have differences in left atrial size, P wave indices, burden of supraventricular ectopy, heart rate, heart rate variability and anthropometric measurements. These differences may relate to variations in atrial morphology, atrial electrophysiology and autonomic function and might help to explain why South Asians are less susceptible to developing AF

Multichannel electrocardiogram diagnostics for the diagnosis of arrhythmogenic right ventricular dysplasia

Aims: The identification of arrhythmogenic right ventricular dysplasia (ARVD) from 12-channel standard electrocardiogram (ECG) is challenging. High density ECG data may identify lead locations and criteria with a higher sensitivity. Methods and results: Eighty-channel ECG recording from patients diagnosed with ARVD and controls were quantified by magnitude and integral measures of QRS and T waves and by a measure (the average silhouette width) of differences in the shapes of the normalized ECG cycles. The channels with the best separability between ARVD patients and controls were near the right ventricular wall, at the third intercostal space. These channels showed pronounced differences in P waves compared to controls as well as the expected differences in QRS and T waves. Conclusion: Multichannel recordings, as in body surface mapping, add little to the reliability of diagnosing ARVD from ECGs. However, repositioning ECG electrodes to a high anterior position can improve the identification of ECG variations in ARVD. Additionally, increased P wave amplitude appears to be associated with ARVD

Intra-cardiac and peripheral levels of biochemical markers of fibrosis in patients undergoing catheter ablation for atrial fibrillation

Aims: Measurement of circulating biomarkers of fibrosis may have a role in selecting patients and treatment strategy for catheter ablation. Pro-collagen type III N-terminal pro-peptide (PIIINP), C-telopeptide of type I collagen (ICTP), fibroblast growth factor 23 (FGF-23), and galectin 3 (gal-3) have all been suggested as possible biomarkers for this indication, but studies assessing whether peripheral levels reflect intra-cardiac levels are scarce. Methods and results: We studied 93 patients undergoing ablation for paroxysmal atrial fibrillation (AF) (n = 63) or non-paroxysmal AF (n = 30). Femoral venous, left and right atrial, and coronary sinus blood were analysed using ELISA to determine biomarker levels. Levels were compared with control patients (n = 36) and baseline characteristics, including left atrial voltage mapping data. C-telopeptide of type I collagen levels were higher in AF than in non-AF patients (P = 0.007). Peripheral ICTP levels were higher than all intra-cardiac levels (P < 0.001). Peripheral gal-3 levels were higher than left atrial levels (P = 0.001). Peripheral levels of FGF-23 and PIIINP were not significantly different from intra-cardiac levels. CS levels of ICTP were higher than right and left atrial levels (P < 0.001). gal-3 was higher in women vs. men (P ≤ 0.001) and with higher body mass index (P ≤ 0.001). ICTP levels increased with reducing ejection fraction (P ≤ 0.012). Conclusions: Atrial fibrillation patients have higher levels of circulating ICTP than matched non-AF controls. In AF ablation patients, intra-cardiac sampling of FGF-23 or PIIINP gives no further information over peripheral sampling. For gal-3 and ICTP, intra-cardiac sampling may be necessary to assess their association with intra-cardiac processes. None of the biomarkers is related to fibrosis assessed by left atrial voltage

Cryoballoon pulmonary vein isolation as first-line treatment of typical atrial flutter: long-term outcomes of the CRAFT trial

\ua9 The Author(s) 2024.Background: CRAFT was an international, multicentre, randomised controlled trial across 11 sites in the United UK and Switzerland. Given the evidence that pulmonary vein triggers may be responsible for atrial flutter (AFL) as well as atrial fibrillation (AF), we hypothesised that cryoballoon pulmonary vein isolation (PVI) would provide greater symptomatic arrhythmia reduction than cavotricuspid isthmus (CTI) ablation, whilst also reducing the subsequent burden of AF. Twelve-month outcomes were previously reported. In this study, we report the extended outcomes of the CRAFT study to 36 months. Methods: Patients with typical AFL and no evidence of AF were randomised 1:1 to cryoballoon PVI or radiofrequency CTI. All patients received an implantable loop recorder (ILR) for continuous cardiac rhythm monitoring. The primary outcome was time-to-symptomatic arrhythmia recurrence &gt; 30 s. Secondary outcomes included time-to-first-AF episode ≥ 2 min. The composite safety outcome included death, stroke and procedural complications. Results: A total of 113 patients were randomised to cryoballoon PVI (n = 54) or radiofrequency CTI ablation (n = 59). Ninety-one patients reconsented for extended follow-up beyond 12 months. There was no difference in the primary outcome between arms, with the primary outcome occurring in 12 PVI vs 11 CTI patients (HR 0.97; 95% CI 0.43–2.20; p = 0.994). AF ≥ 2 min was significantly less frequent in the PVI arm, affecting 26 PVI vs 36 CTI patients (HR 0.48; 95% CI 0.29–0.79; p = 0.004). The composite safety outcome occurred in 5 PVI and 6 CTI patients (p = 0.755). Conclusion: Cryoballoon PVI shows similar efficacy to radiofrequency CTI ablation in reducing symptomatic arrhythmia recurrence in patients presenting with isolated typical AFL but significantly reduces the occurrence of subsequent AF. Graphical Abstract: (Figure presented.)

Circulating Matrix Metalloproteinase-9 Is Associated with Cardiovascular Risk Factors in a Middle-Aged Normal Population

Background: Elevated levels of circulating matrix metalloproteinase-9 (MMP-9) have been demonstrated in patients with established coronary artery disease (CAD). The aim of this study was to analyse levels of MMP-9 in a population free from symptomatic CAD and investigate their associations with cardiovascular (CV) risk factors, including C-reactive protein (CRP).   Methods: A cross-sectional study was performed in a population based random sample aged 45–69 (n = 345, 50% women). MMP-9 levels were measured in EDTA-plasma using an ELISA-method. CV risk factors were measured using questionnaires and standard laboratory methods. Results: Plasma MMP-9 was detectable in all participants, mean 38.9 ng/mL (SD 22.1 ng/mL). Among individuals without reported symptomatic CAD a positive association (p&lt;0.001) was seen, for both men and women, of MMP-9 levels regarding total risk load of eight CV risk factors i.e. blood pressure, dyslipidemia, diabetes, obesity, smoking, alcohol intake, physical activity and fruit and vegetable intake. The association was significant also after adjustment for CRP, and was not driven by a single risk factor alone. In regression models adjusted for age, sex, smoking, alcohol intake and CRP, elevated MMP-9 levels were independently positively associated with systolic blood pressure (p = 0.037), smoking (p&lt;0.001), alcohol intake (p = 0.003) and CRP (p&lt;0.001). The correlation coefficient between MMP-9 and CRP was r = 0.24 (p&lt;0.001).   Conclusions: In a population without reported symptomatic CAD, MMP-9 levels were associated with total CV risk load as well as with single risk factors. This was found also after adjustment for CRP  Original Publication: Peter Garvin, Lennart Nilsson, John Carstensen, Lena Jonasson and Margareta Kristenson, Circulating Matrix Metalloproteinase-9 Is Associated with Cardiovascular Risk Factors in a Middle-Aged Normal Population, 2008, PLoS ONE, (3), 3, e1774. http://dx.doi.org/10.1371/journal.pone.0001774 Licensee: Public Library of Science (PLoS) http://www.plos.org/</p

Increased Levels of Leukocyte-Derived MMP-9 in Patients with Stable Angina Pectoris

Objective: There is a growing interest for matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in plasma as novel biomarkers in coronary artery disease (CAD). We aimed to identify the sources of MMP-8, MMP-9, TIMP-1 and TIMP-2 among peripheral blood cells and further explore whether gene expression or protein release was altered in patients with stable angina pectoris (SA). Methods: In total, plasma MMP-9 was measured in 44 SA patients and 47 healthy controls. From 10 patients and 10 controls, peripheral blood mononuclear cells (PBMC) and neutrophils were isolated and stimulated ex vivo. MMPs, TIMPs and myeloperoxidase were measured in plasma and supernatants by ELISA. The corresponding gene expression was measured by real-time PCR. Results: Neutrophils were the dominant source of MMP-8 and MMP-9. Upon moderate stimulation with IL-8, the neutrophil release of MMP-9 was higher in the SA patients compared with controls (p,0.05). In PBMC, the TIMP-1 and MMP-9 mRNA expression was higher in SA patients compared with controls, p,0.01 and 0.05, respectively. There were no differences in plasma levels between patients and controls except for TIMP-2, which was lower in patients, p,0.01. Conclusion: Measurements of MMPs and TIMPs in plasma may be of limited use. Despite similar plasma levels in SA patients and controls, the leukocyte-derived MMP-9 and TIMP-1 are significantly altered in patients. The findings indicate that th