Adrian D. Elliott

Long-term effect of goal-directed weight management in an atrial fibrillation cohort: A long-term follow-up study (LEGACY)

BACKGROUND Obesity and atrial fibrillation (AF) frequently coexist. Weight loss reduces the burden of AF, but whether this is sustained, has a dose effect, or is influenced by weight fluctuation is unknown. OBJECTIVES This study sought to evaluate the long-term impact of weight loss and weight fluctuation on rhythm control in obese individuals with AF. METHODS Of 1,415 consecutive patients with AF, 825 had a body mass index ≥ 27 kg/m(2) and were offered weight management. After screening for exclusion criteria, 355 were included in this analysis. Weight loss was categorized as group 1 (≥ 10%), group 2 (3% to 9%), and group 3 (<3%). Weight trend and/or fluctuation was determined by yearly follow-up. We determined the impact on the AF severity scale and 7-day ambulatory monitoring. RESULTS There were no differences in baseline characteristics or follow-up among the groups. AF burden and symptom severity decreased more in group 1 compared with groups 2 and 3 (p < 0.001 for all). Arrhythmia-free survival with and without rhythm control strategies was greatest in group 1 compared with groups 2 and 3 (p < 0.001 for both). In multivariate analyses, weight loss and weight fluctuation were independent predictors of outcomes (p < 0.001 for both). Weight loss ≥ 10% resulted in a 6-fold (95% confidence interval: 3.4 to 10.3; p < 0.001) greater probability of arrhythmia-free survival compared with the other 2 groups. Weight fluctuation >5% partially offset this benefit, with a 2-fold (95% confidence interval: 1.0 to 4.3; p = 0.02) increased risk of arrhythmia recurrence. CONCLUSIONS Long-term sustained weight loss is associated with significant reduction of AF burden and maintenance of sinus rhythm. (Long-Term Effect of Goal directed weight management on Atrial Fibrillation Cohort: A 5 Year follow-up study [LEGACY Study]; ACTRN12614001123639).

Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in Obese Individuals With Atrial Fibrillation: The CARDIO-FIT Study.

BACKGROUND Obesity begets atrial fibrillation (AF). Although cardiorespiratory fitness is protective against incident AF in obese individuals, its effect on AF recurrence or the benefit of cardiorespiratory fitness gain is unknown. OBJECTIVES This study sought to evaluate the role of cardiorespiratory fitness and the incremental benefit of cardiorespiratory fitness improvement on rhythm control in obese individuals with AF. METHODS Of 1,415 consecutive patients with AF, 825 had a body mass index ≥27 kg/m(2) and were offered risk factor management and participation in a tailored exercise program. After exclusions, 308 patients were included in the analysis. Patients underwent exercise stress testing to determine peak metabolic equivalents (METs). To determine a dose response, cardiorespiratory fitness was categorized as: low (<85%), adequate (86% to 100%), and high (>100%). Impact of cardiorespiratory fitness gain was ascertained by the objective gain in fitness at final follow-up (≥2 METs vs. <2 METs). AF rhythm control was determined using 7-day Holter monitoring and AF severity scale questionnaire. RESULTS There were no differences in baseline characteristics or follow-up duration between the groups defined by cardiorespiratory fitness. Arrhythmia-free survival with and without rhythm control strategies was greatest in patients with high cardiorespiratory fitness compared to adequate or low cardiorespiratory fitness (p < 0.001 for both). AF burden and symptom severity decreased significantly in the group with cardiorespiratory fitness gain ≥2 METs as compared to <2 METs group (p < 0.001 for all). Arrhythmia-free survival with and without rhythm control strategies was greatest in those with METs gain ≥2 compared to those with METs gain <2 in cardiorespiratory fitness (p < 0.001 for both). CONCLUSIONS Cardiorespiratory fitness predicts arrhythmia recurrence in obese individuals with symptomatic AF. Improvement in cardiorespiratory fitness augments the beneficial effects of weight loss. (Evaluating the Impact of a Weight Loss on the Burden of Atrial Fibrillation [AF] in Obese Patients; ACTRN12614001123639).

Interval training versus continuous exercise in patients with coronary artery disease: a meta-analysis.

BACKGROUND High aerobic capacity is inversely related to cardiovascular disease morbidity and mortality. Recent studies suggest greater improvements in aerobic capacity with high-intensity interval training (interval) compared to moderate-intensity continuous aerobic exercise (continuous). Therefore we perform a meta-analysis of randomised controlled trials comparing the effectiveness of INTERVAL versus CONTINUOUS in aerobic capacity, amongst patients with stable coronary artery disease (CAD) and preserved ejection fraction METHODS We searched PubMed, EMBASE, CINAHL, the Australia and New Zealand Clinical Trials Register, clinicaltrials.gov and TROVE for randomised controlled trials comparing INTERVAL with CONTINUOUS in patients with CAD. Studies published in the English language up to December 2013 were eligible for inclusion. Aerobic capacity, quantified by peak oxygen consumption (VO2peak) post exercise training was extracted and compared post-intervention between INTERVAL and CONTINUOUS by way of a fixed model meta-analysis. Secondary outcomes including anaerobic threshold, blood pressure and high-density lipoproteins (HDL) were also analysed. RESULTS Six independent studies with 229 patients (n=99 randomised to INTERVAL) were included in the meta-analysis. There was a significantly higher increase in VO2peak following INTERVAL compared to CONTINUOUS (Weighted Mean Difference=1.53 ml•kg(-1)min(-1), 95% CI 0.84 to 2.23) with homogeneity displayed between studies (Chi Squared=2.69; P=0.7). Significant effects of INTERVAL compared to CONTINUOUS were also found for anaerobic threshold but not systolic blood pressure. CONCLUSION In patients with CAD, INTERVAL appears more effective than CONTINUOUS for the improvement of aerobic capacity in patients with CAD. However, long-term studies assessing morbidity and mortality following INTERVAL are required before this approach can be more widely adopted.

The right ventricle following prolonged endurance exercise: are we overlooking the more important side of the heart? A meta-analysis

Aims Prolonged endurance exercise is associated with elevated biomarkers associated with myocardial damage and modest evidence of left ventricular (LV) dysfunction. Recent studies have reported more profound effects on right ventricular (RV) function following endurance exercise. We performed a meta-analysis of studies reporting RV function pre-endurance and postendurance exercise. Methods We performed a search of peer-reviewed studies with the criteria for inclusion in the analysis being (1) healthy adult participants; (2) studies examining RV function following an event of at least 90 min duration; (3) studies reporting RV fractional area change (RVFAC), RV strain (S), RV ejection fraction (RVEF) or tricuspid annular plane systolic excursion (TAPSE) and (4) studies evaluating RV function immediately (<1 h) following exercise. Results Fourteen studies were included with 329 participants. A random-effects meta-analysis revealed significant impairments of RV function when assessed by RVFAC (weighted mean difference (WMD) −5.78%, 95% CI −7.09% to −4.46%), S (WMD 3.71%, 95% CI 2.79% to 4.63%), RVEF (WMD −7.05%, 95% CI −12.3% to −1.8%) and TAPSE (WMD −4.77 mm, 95% CI −8.3 to −1.24 mm). Modest RV dilation was evident in studies reporting RV systolic area postexercise (WMD 1.79 cm2, 95% CI 0.5 to 3.08 cm2). In contrast, no postexercise changes in LV systolic function (expressed as LVFAC or LVEF) were observed in the included studies (standardised mean difference 0.03%, 95% CI −0.13% to 0.18%). Conclusions Intense prolonged exercise is associated with a measurable reduction in RV function while LV function is relatively unaffected. Future studies should examine the potential clinical consequences of repeated prolonged endurance exercise on the right ventricle.

Integrated care in atrial fibrillation: a systematic review and meta-analysis

Objective Atrial fibrillation (AF) is an emerging global epidemic associated with significant morbidity and mortality. Whilst other chronic cardiovascular conditions have demonstrated enhanced patient outcomes from coordinated systems of care, the use of this approach in AF is a comparatively new concept. Recent evidence has suggested that the integrated care approach may be of benefit in the AF population, yet has not been widely implemented in routine clinical practice. We sought to undertake a systematic review and meta-analysis to evaluate the impact of integrated care approaches to care delivery in the AF population on outcomes including mortality, hospitalisations, emergency department visits, cerebrovascular events and patient-reported outcomes. Methods PubMed, Embase and CINAHL databases were searched until February 2016 to identify papers addressing the impact of integrated care in the AF population. Three studies, with a total study population of 1383, were identified that compared integrated care approaches with usual care in AF populations. Results Use of this approach was associated with a reduction in all-cause mortality (OR 0.51, 95% CI 0.32 to 0.80, p=0.003) and cardiovascular hospitalisations (OR 0.58, 95% CI 0.44 to 0.77, p=0.0002) but did not significantly impact on AF-related hospitalisations (OR 0.82, 95% CI 0.56 to 1.19, p=0.29) or cerebrovascular events (OR 1.00, 95% CI 0.48 to 2.09, p=1.00). Conclusions The use of the integrated care approach in AF is associated with reduced cardiovascular hospitalisations and all-cause mortality. Further research is needed to identify optimal settings, methods and components of delivering integrated care to the burgeoning AF population.

Subclinical device-detected atrial fibrillation and stroke risk: a systematic review and meta-analysis

Aims To determine stroke risk in subclinical atrial fibrillation (AF) and temporal association between subclinical AF and stroke. Methods and results Pubmed/Embase was searched for studies reporting stroke in subclinical AF in patients with cardiac implantable electronic devices (CIEDs). After exclusions, 11 studies were analysed. Of these seven studies reported prevalence of subclinical AF, two studies reported association between subclinical and clinical AF, seven studies reported stroke risk in subclinical AF, and five studies reported temporal relationship between subclinical AF and stroke. Subclinical AF was noted after CIEDs implant in 35% [interquartile range (IQR) 34-42] of unselected patients with pacing indication over 1-2.5 years. The definition and cut-off duration (for stroke risk) of subclinical AF varied across studies. Subclinical AF was strongly associated with clinical AF (OR 5.7, 95% CI 4.0-8.0, P < 0.001, I2 = 0%). The annual stroke rate in patients with subclinical AF > defined cut-off duration was 1.89/100 person-year (95% CI 1.02-3.52) with 2.4-fold (95% CI 1.8-3.3, P < 0.001, I2 = 0%) increased risk of stroke as compared to patients with subclinical AF < cut-off duration (absolute risk was 0.93/100 person-year). Three studies provided mean CHADS2 score. In these studies, with mean CHADS2 score of 2.1 ± 0.1, subclinical AF was associated with annual stroke rate of 2.76/100 person-years (95% CI 1.46-5.23). After excluding patients without AF, only 17% strokes occurred in presence of ongoing AF. Subclinical AF was noted in 29% [IQR 8-57] within 30 days preceding stroke. Conclusion Subclinical AF strongly predicts clinical AF and is associated with elevated absolute stroke risk albeit lower than risk described for clinical AF.

Concomitant Obesity and Metabolic Syndrome Add to the Atrial Arrhythmogenic Phenotype in Male Hypertensive Rats

Background Besides hypertension, obesity and the metabolic syndrome have recently emerged as risk factors for atrial fibrillation. This study sought to delineate the development of an arrhythmogenic substrate for atrial fibrillation in hypertension with and without concomitant obesity and metabolic syndrome. Methods and Results We compared obese spontaneously hypertensive rats (SHR‐obese, n=7–10) with lean hypertensive controls (SHR‐lean, n=7–10) and normotensive rats (n=7–10). Left atrial emptying function (MRI) and electrophysiological parameters were characterized before the hearts were harvested for histological and biochemical analyses. At the age of 38 weeks, SHR‐obese, but not SHR‐lean, showed increased body weight and impaired glucose tolerance together with dyslipidemia compared with normotensive rats. Mean blood pressure was similarly increased in SHR‐lean and SHR‐obese when compared with normotensive rats (178±9 and 180±8 mm Hg [not significant] versus 118±5 mm Hg, P<0.01 for both), but left ventricular end‐diastolic pressure was more increased in SHR‐obese than in SHR‐lean. Impairment of left atrial emptying function, increase in total atrial activation time, and conduction heterogeneity, as well as prolongation of inducible atrial fibrillation durations, were more pronounced in SHR‐obese as compared with SHR‐lean. Histological and biochemical examinations revealed enhanced triglycerides and more pronounced fibrosis in the left atrium of SHR‐obese. Besides increased expression of profibrotic markers in SHR‐lean and SHR‐obese, the profibrotic extracellular matrix protein osteopontin was highly upregulated only in SHR‐obese. Conclusions In addition to hypertension alone, concomitant obesity and metabolic syndrome add to the atrial arrhythmogenic phenotype by impaired left atrial emptying function, local conduction abnormalities, interstitial atrial fibrosis formation, and increased propensity for atrial fibrillation.

Lifestyle management to prevent and treat atrial fibrillation

ABSTRACT Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia with a one in four lifetime risk in adults over the age of forty. Traditionally, AF management has focused on the three pillars of rate control, rhythm control and appropriate anticoagulation to reduce stroke risk. More recently, the importance of cardiovascular risk factor management in AF has emerged as a fourth and essential pillar with improved patient outcomes. Areas covered: Here, we aim to summarize the current available evidence for the association between various modifiable risk factors and AF, and to identify optimal treatment targets to improve outcomes. Expert Commentary: Care for AF patients utilizing an integrated approach and aggressive lifestyle management may reduce the enormous burden of this arrhythmia.

Alcohol and incident atrial fibrillation – A systematic review and meta-analysis

BACKGROUND Whilst high levels of alcohol consumption are known to be associated with atrial fibrillation (AF), it is unclear if any level of alcohol consumption can be recommended to prevent the onset of the condition. The aim of this review is to characterise the association between chronic alcohol intake and incident AF. METHODS AND RESULTS Electronic literature searches were undertaken using PubMed and Embase databases up to 1 February 2016 to identify studies examining the impact of alcohol on the risk of incident AF. Prospective studies reporting on at least three levels of alcohol intake and published in English were eligible for inclusion. Studies of a retrospective or case control design were excluded. The primary study outcome was development of incident AF. Consistent with previous studies, high levels of alcohol intake were associated with an increased incident AF risk (HR 1.34, 95% CI 1.20-1.49, p<0.001). Moderate levels of alcohol intake were associated with a heightened AF risk in males (HR 1.26, 95% CI 1.04-1.54, p=0.02) but not females (HR 1.03, 95% CI 0.86-1.25, p=0.74). Low alcohol intake, of up to 1 standard drink (SD) per day, was not associated with AF development (HR 0.95, 95% CI 0.85-1.06, p=0.37). CONCLUSIONS Low levels of alcohol intake are not associated with the development of AF. Gender differences exist in the association between moderate alcohol intake and AF with males demonstrating greater increases in risk, whilst high alcohol intake is associated with a heightened AF risk across both genders.

Molecular mechanisms of atrial fibrosis: implications for the clinic

ABSTRACT Introduction: Recent research has unravelled an increasing list of cardiac conditions and risk factors that may be responsible for the abnormal underlying atrial substrate that predisposes to atrial fibrillation (AF). Atrial fibrosis has been demonstrated as the pivotal structural abnormality underpinning conduction disturbances that promote AF in different disease models. Despite the advancement in our discoveries of the molecular mechanisms involved in the profibrotic milieu, targeted therapeutics against atrial fibrosis remain lacking. Areas covered: This review is focused on detailing the key molecular signalling pathways that contribute to atrial fibrosis including: angiotensin II, transforming growth factor (TGF- ß1), connective tissue growth factor (CTGF) and endothelin-1. We also discussed the potential therapeutic options that may be useful in modulating the abnormal atrial substrate. In addition, we examined the new paradigm of AF care in lifestyle and risk factor management that has been shown to arrest and reverse the atrial remodelling process leading to improved AF outcomes. Expert commentary: The future of AF care is likely to require an integrated approach consisting of aggressive risk factor management in addition to the established paradigm of rate and rhythm management and anticoagulation. Translational studies on molecular therapeutics to combat atrial fibrosis is urgently needed.