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Background: Mineralocorticoid receptor antagonists (MRAs) have emerged as potential therapy to target the underlying arrhythmogenic substrate in atrial fibrillation (AF). Nevertheless, there have been inconsistent results on the impact of MRAs on AF., Objective: We sought to evaluate the effect of MRAs on AF incidence and progression in patients with and without heart failure., Methods: Electronic databases were searched up to September, 2022 for randomized controlled trials (RCTs) that evaluated MRA use and reported AF outcomes. Primary outcome was a composite of new-onset or recurrent AF. Safety outcomes included hyperkalemia and gynecomastia risks. A random-effects meta-analysis estimated pooled odds ratios (OR) and 95% confidence intervals (CI)., Results: 12 RCTs, comprising 11,419 patients treated with various MRAs were included [5960 (52%) on MRA]. On follow-up (6-39 months), 714 (5.5%) patients developed AF. MRA therapy was associated with a 32% reduction in the risk of new-onset or recurrent AF [OR 0.68 (95% CI 0.51-0.92), I 2  = 40%]. On subgroup analysis, the greatest benefit magnitude was demonstrated in reducing AF recurrence [OR 0.50 (95% CI 0.30-0.83)] and among patients with left ventricular dysfunction [OR 0.59 (95% CI 0.40-0.85)]. Gynecomastia, but not hyperkalemia, was associated with MRA use. Meta-regression analysis demonstrated that therapy duration was a significant interaction factor driving the effect size (P interaction  = 0.013)., Conclusion: MRA use is associated with a reduction in AF risk, especially AF progression. A prominent effect is seen in patients with heart failure, further augmented by therapy duration. Prospective trials are warranted to evaluate MRA use as upstream therapy for preventing this common arrhythmia., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with atrial fibrillation (AF) represents a significant clinical challenge. Two diagnostic scoring tools have been developed to aid the noninvasive diagnosis of HFpEF: the HFA-PEFF (Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology) and the H 2 FPEF scoring systems., Objectives: The purpose of this study was to evaluate the performance of these 2 scoring tools for the diagnosis of HFpEF against a gold standard of invasive evaluation in a cohort of patients with AF., Methods: The authors recruited consecutive patients with symptomatic AF and preserved ejection fraction who were scheduled for an AF ablation procedure. Gold-standard invasive diagnosis of HFpEF was performed at the AF ablation procedure using mean left atrial pressure at rest and following infusion of 500 mL fluid. Each participant was scored according to the noninvasive HFA-PEFF and H 2 FPEF scoring systems. Sensitivity and specificity analyses were performed to assess the accuracy of these scoring systems in diagnosing HFpEF., Results: In total, 120 participants were recruited. HFpEF was diagnosed invasively in 88 (73.3%) participants, whereas 32 (26.7%) had no HFpEF. Using the HFA-PEFF score, 38 (31.7%) participants had a high probability of HFpEF and 82 (68.3%) had low/intermediate probability of HFpEF. Using the H 2 FPEF tool, 72 (60%) participants had a high probability of HFpEF and 48 (40%) had intermediate probability. A high HFA-PEFF (≥5 points) score could diagnose HFpEF with a sensitivity of 40% and a specificity of 91%, and a high H 2 FPEF score (≥6 points) could diagnose HFpEF with a sensitivity of 69% and specificity of 66%. Overall diagnostic accuracy was similar using both tools (AUC: 0.663 vs 0.707, respectively; P = 0.636)., Conclusions: Against a gold standard of invasively diagnosed HFpEF, the HFA-PEFF and H 2 FPEF scores demonstrate only moderate accuracy in patients with AF and should be utilized with caution in this cohort of patients. (Characterising Left Atrial Function and Compliance in Atrial Fibrillation; ACTRN12620000639921)., Competing Interests: Funding Support and Author Disclosures Drs Ariyaratnam, Mishima, Kadhim, Emami, Fitzgerald, Stokes, and Thiyagarajah are supported by Postgraduate Scholarships from the University of Adelaide. Dr Sanders is supported by a Practitioner Fellowship from the National Health and Medical Research Council of Australia; and the University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic, Boston Scientific, and Abbott Medical, and research funding from Medtronic, Abbott Medical, Boston Scientific, and Microport CRM. Dr Elliott is supported by a Future Leader Fellowship from the National Heart Foundation of Australia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac resynchronization therapy (CRT) is typically attempted with biventricular (BiV) pacing. One-third of patients are nonresponders. Left bundle branch area pacing (LBBAP) has been evaluated as an alternative means., Objective: The purpose of this study was to assess the feasibility and clinical response of permanent LBBAP as an alternative to BiV pacing., Methods: Of 479 consecutive patients referred with heart failure, 50 with BiV-CRT and 51 with LBBAP-CRT were included in this analysis after study exclusions. Quality-of-Life (QoL) assessments, echocardiographic measurements, and New York Heart Association (NYHA) class were obtained at baseline and at 6-monthly intervals., Results: There were no differences in baseline characteristics between groups (all P > .05). Clinical outcomes such as left ventricular ejection fraction, left ventricular end-systolic volume, QoL, and NYHA class were significantly improved for both pacing groups compared to baseline. The LBBAP-CRT group showed greater improvement in left ventricular ejection fraction at 6 months (P = .001) and 12 months (P = .021), accompanied by greater reduction in left ventricular end-systolic volume (P = .007). QRS duration < 120 ms (baseline 160.82 ± 21.35 ms vs 161.08 ± 24.48 ms) was achieved in 30% in the BiV-CRT group vs 71% in the LBBAP-CRT group (P ≤ .001). Improvement in NYHA class (P = .031) and QoL index was greater (P = .014). Reduced heart failure admissions (P = .003) and health care utilization (P < .05) and improved lead performance (P < .001) were observed in the LBBAP-CRT group., Conclusion: LBBAP-CRT is feasible and effective CRT. It results into a meaningful improvement in QoL and reduction in health care utilization. This can be offered as an alternative to BiV-CRT or potentially as first-line therapy., Competing Interests: Disclosures Dr Pathak reports having served on the advisory board of Medtronic, Abbott, Boston Scientific, and Biotronik. Dr Pathak reports that Canberra Heart Rhythm Foundation/Australian National University has received on his behalf lecture and/or consulting fees and research funding from Medtronic, Abbott Medical, Boston Scientific, and Biotronik. Dr Sanders reports having served on the advisory board of Medtronic, Abbott Medical, Boston Scientific, CathRx, and PaceMate. Dr Sanders reports that the University of Adelaide has received on his behalf lecture/consulting fees and/or research funding from Medtronic, Abbott Medical, Boston Scientific, and MicroPort. All other authors have no disclosures., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) commonly coexist. We hypothesize that patients with symptomatic AF but without overt clinical HF commonly exhibit subclinical HFpEF according to established hemodynamic criteria., Objectives: The authors sought to use invasive hemodynamics to investigate the prevalence and implications of subclinical HFpEF in AF ablation patients., Methods: Consecutive symptomatic AF ablation patients were prospectively recruited. Diagnosis of subclinical HFpEF was undertaken by invasive assessment of left atrial pressure (LAP). Participants had HFpEF if the baseline mean LAP was >15 mm Hg and early HFpEF if the mean LAP was >15 mm Hg after a 500-mL fluid challenge. LA compliance was assessed invasively by monitoring the LAP and LA diameter during direct LA infusion of 15 mL/kg normal saline. LA compliance was calculated as Δ LA diameter/ΔLAP. LA cardiomyopathy was further studied with exercise echocardiography and electrophysiology study. Functional impact was evaluated using cardiopulmonary exercise testing and the AF Symptom Severity questionnaire., Results: Of 120 participants, 57 (47.5%) had HFpEF, 31 (25.8%) had early HFpEF, and 32 (26.7%) had no HFpEF. Both HFpEF and early HFpEF were associated with lower LA compliance compared with those without HFpEF (P < 0.001). Participants with HFpEF and early HFpEF also displayed decreased LA emptying fraction (P = 0.004), decreased LA voltage (P = 0.001), decreased VO 2peak (P < 0.001), and increased AF symptom burden (P = 0.002) compared with those without HFpEF., Conclusions: Subclinical HFpEF is common in AF ablation patients and is characterized by a LA cardiomyopathy, decreased cardiopulmonary reserve and increased symptom burden. The diagnosis of HFpEF may identify patients with AF with the potential to benefit from novel HFpEF therapies. (Characterising Left Atrial Function and Compliance in Atrial Fibrillation; ACTRN12620000639921)., Competing Interests: Funding Support and Author Disclosures Drs Ariyaratnam, Mishima, Kadhim, Emami, Malik, and Fitzgerald are supported by Postgraduate Scholarships from the University of Adelaide. Dr Elliott is supported by a Future Leader Fellowship from the National Heart Foundation of Australia. Dr Gallagher is supported by a Postdoctoral Fellowship from the University of Adelaide. Dr Lau is supported by a Mid-career fellowship from The Hospital Research Foundation. Dr Sanders is supported by a Practitioner Fellowship from the National Health and Medical Research Council of Australia. Dr Lau reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Abbott Medical, Bayer, Biotronik, BMS Pfizer, Boehringer Ingelheim, Medtronic, and MicroPort CRM. Dr Sanders has served on the advisory board of Medtronic, Abbott Medical, Boston-Scientific, Pacemate, and CathRx. Dr Sanders reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic, Boston-Scientific, and Abbott Medical; and reports that the University of Adelaide has received on his behalf research funding from Medtronic, Abbott Medical, Boston Scientific, and Microport CRM. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

The left atrium (LA) plays a critical role in receiving pulmonary venous return and modulating left ventricular (LV) filling. With the onset of exercise, LA function contributes to the augmentation in stroke volume. Due to the growing focus on atrial imaging, there is now evidence that structural remodeling and dysfunction of the LA is associated with adverse outcomes including incident cardiovascular disease. In patients with established disease, pathological changes in atrial structure and function are associated with exercise intolerance, increased hospital admissions and mortality, independent of left ventricular function. Exercise training is widely recommended in patients with cardiovascular disease to improve patient outcomes and maintain functional capacity. There are widely documented changes in LV function with exercise, yet less attention has been given to the LA. In this review, we first describe LA physiology at rest and during exercise, before exploring its association with cardiac disease outcomes including atrial fibrillation, heart failure, and stroke. The adaptation of the LA to short- and longer-term exercise training is evaluated through review of longitudinal studies of exercise training in healthy participants free of cardiovascular disease and athletes. We then consider the changes in LA structure and function among patients with established disease, where adverse atrial remodeling may be implicated in the disease process. Finally, we consider important future directions for assessment of atrial structure and function using novel imaging modalities, in response to acute and chronic exercise.

Background: Reduced biventricular pacing (BiVP) is a common phenomenon in cardiac resynchronization therapy (CRT) with impact on CRT-response and patients' prognosis. Data on treatment strategies for patients with ventricular arrhythmia and BiVP reduction is sparse. We sought to assess the effects of ventricular arrhythmia treatment on BiVP., Methods: In this retrospective analysis, the data of CRT patients with a reduced BiVP ≤ 97% due to ventricular arrhythmia were analyzed. Catheter ablation or intensified medical therapy was performed to optimize BiVP., Results: We included 64 consecutive patients (73 ± 10 years, 89% male, LVEF 30 ± 7%). Of those, 22/64 patients (34%) underwent ablation of premature ventricular contractions (PVC) and 15/64 patients (23%) underwent ventricular tachycardia (VT) ablation while 27/64 patients (42%) received intensified medical treatment. Baseline BiVP was 88.1% ± 10.9%. An overall increase in BiVP percentage points of 8.8% (range - 5 to + 47.6%) at 6-month follow-up was achieved. No changes in left ventricular function were observed but improvement in BiVP led to an improvement in NYHA class in 24/64 patients (38%). PVC ablation led to a significantly better improvement in BiVP [9.9% (range 4 to 22%) vs. 3.2% (range - 5 to + 10.7%); p =  < 0.001] and NYHA class (12/22 patients vs. 4/27 patients; p = 0.003) than intensified medical therapy. All patients with VT and reduced BiVP underwent VT ablation with an increase of BiVP of 16.3 ± 13.4%., Conclusion: In this evaluation of ventricular arrhythmia treatment aiming for CRT optimization, both medical therapy and catheter ablation were shown to be effective. Compared to medical therapy, a higher increase in BiVP was observed after PVC ablation, and more patients improved in NYHA class., Clinical Trial Registration: The study was registered at clinical trials.org in August 2019: NCT04065893., (© 2022. The Author(s).)

Aims: Heart failure patients with mid-range ejection fraction (HFmrEF) have overlapping clinical features, compared with patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). We aim to perform a meta-analysis of studies reporting long-term outcomes in HFmrEF compared with HFrEF and HFpEF., Methods and Results: Data from 18 eligible large-scale studies including 126 239 patients were pooled. Patients with HFmrEF had a lower risk of all-cause death than those with HFrEF [risk ratio (RR) = 0.92; 95% CI = 0.85-0.98; P < 0.001]. This significant difference was seen in the follow-up at 1, 2, and 3 years. Patients with HFmrEF had significantly lower risk of cardiovascular (CV) deaths than HFrEF (RR = 0.77; 95% CI = 0.65-0.92; P < 0.001). Subgroup analysis showed that studies recruiting >50% of males had higher risk of deaths with HFrEF (RR = 1.15; 95% CI = 1.04-1.26; P = 0.006). When compared with HFpEF, patients with HFmrEF had comparable risk of all-cause death (RR = 1.02; 95% CI = 0.96-1.09; P = 0.53). Similarly, there were no differences in the 1, 2, and 3 year deaths; CV and non-CV deaths were insignificant between HFmrEF and HFpEF., Conclusions: The results of the study support that HFmrEF has better prognosis than HFrEF but similar prognosis when compared with HFpEF. Gender disparity between studies seems to influence the results between HFmrEF and HFrEF. Transition in left ventricular ejection fraction (LVEF), which could not be addressed in the study, may play a decisive role in determining outcomes. PROSPERO review registration number CRD42021277107., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Methamphetamine-associated cardiomyopathy (MA-CMP) is an increasingly recognised aetiology of cardiomyopathy. Cardiovascular magnetic resonance (CMR) is a specialised cardiac imaging modality commonly used in assessment of cardiomyopathy. We aimed to identify specific CMR features associated with MA-CMP., Methods: A retrospective cohort study of CMR scans was performed in a single centre between January 2015 and December 2020. Thirty patients with MA-CMP who had undergone CMR were identified. MA-CMP was defined as those with a history of significant methamphetamine use hospitalised with acute decompensated heart failure (other causes of cardiomyopathy excluded). A retrospective analysis of index admission CMRs was performed. All studies were performed on a 1.5 T CMR scanner., Results: The mean age of MA-CMP patients was 43.7 ± 7.5 years, and 86.7% were male. The mean left ventricular (LV) volume obtained in this cohort was consistent with severe LV dilatation (LV end-diastolic volume (334 ± 99 ml); LV end-systolic volume: 269 ± 98 ml), whilst the right ventricular (RV) volume indicated moderate-to-severe dilatation (RV end-diastolic volume: 272 ± 91 ml; RV end-systolic volume: 173 ± 82 ml). Mean LV ejection fraction (20.9 ± 9.2%) indicated severe LV dysfunction, with moderate-to-severe RV dysfunction also detected (RV ejection fraction: 29.4 ± 13.4%). 22 patients (73.3%) had myocardial late gadolinium enhancement (LGE), of which 59.1% were located in the mid-wall, with all of these involving the interventricular septum. 22.7% displayed localised regions of sub-endocardial LGE in a variety of locations, and 18.2% had transmural regions of LGE that were located in the inferior and inferolateral segments. 6 patients (20%) had intracardiac thrombus (4 LV, 2 both LV and RV)., Conclusion: MA-CMP was associated with severe biventricular dilatation and dysfunction, with a high prevalence of intraventricular thrombus. This cohort study highlights that MA-CMP patients have a high prevalence of CMR findings., (© 2022. The Author(s).)

Atrial fibrillation (AF) is the most common cardiac tachyarrhythmia and has a rising global prevalence. Given the increasing burden of AF-related symptoms and complications, new approaches to management are required. Anemia and iron deficiency are common conditions in patients with AF. Furthermore, emerging evidence suggests that the presence of anemia may be associated with worse outcome in these patients. The role of anemia and iron deficiency has been extensively explored in other cardiovascular states, such as heart failure and ischemic heart disease. In particular, the role of iron repletion amongst patients with heart failure is now an established treatment modality. However, despite the strong bidirectional inter-relationship between AF and heart failure, the implications of anemia and iron-deficiency in AF have been scarcely studied. This area is of mechanistic and clinical relevance given the potential that treatment of these conditions may improve symptoms and prognosis in the increasing number of individuals with AF. In this review, we summarise the current published literature on anemia and iron deficiency in patients with AF. We discuss AF complications such as stroke, bleeding, and heart failure, in addition to AF-related symptoms such as exercise intolerance, and the potential impact of anemia and iron deficiency on these. Finally, we summarize current research gaps on anemia, iron deficiency, and AF, and underscore potential research directions., (© 2022. The Author(s).)

The growth in methamphetamine usage worldwide continues to present increasing societal and health care challenges. With the escalation of its usage in a variety of social demographics, the entity of methamphetamine-associated cardiomyopathy (MA-CMP) has emerged. This entity is increasingly responsible for an important proportion of heart failure burden in both admissions to hospital and in those individuals requiring chronic heart failure care. MA-CMP poses some unique challenges including its recognition, particularly in younger patients presenting with new-onset heart failure, its severity at presentation and complications as well as management options. The challenging nature of methamphetamine addiction and the necessity to achieve abstinence is a fundamental aspect of management of this condition. As methamphetamine use continues at high levels in Australia, the burden of MA-CMP will inevitably increase and, therefore, all clinicians responsible for heart failure management require an awareness of this disease entity and the specific clinical challenges of its care., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Background: The value of antiarrhythmics to maintain normal sinus rhythm in patients with atrial fibrillation (AF) and heart failure (HF) is still being debated. We aimed to determine whether rhythm control using antiarrhythmic drugs (AADs) is more effective than rate control in improving outcomes in this population., Method: In this sub-analysis of the CASTLE-AF study, we included patients that were treated pharmacologically either to maintain sinus rhythm or to achieve rate control. The primary endpoint was defined as a composite of death from any cause or worsening of HF that led to an unplanned overnight hospitalization., Result: Among 210 patients (mean age of 64.1 ± 10.8 years, 83.3% male) treated pharmacologically, 60 patients were in the rhythm control group and 150 were in the rate control group. Patients in the rhythm control group were less likely to be assigned a beta-blocker (53 (88.3%) vs 141 (97.9%), P = 0.004) and digitalis (8 (13.3%) vs 53 (36.8%), P < 0.001). Over a median follow-up of 3.76 (95% confidence interval (CI), 3.23, 4.48) years, the primary composite endpoint of all-cause mortality and HF admissions occurred in 23 patients (38.3%) in the rhythm control arm vs 67 (44.7%) in the rate control arm (hazard ratio, 0.99; 95% CI, 0.62 to 1.60; P = 0.976)., Conclusion: In CASTLE-AF among AF patients with HF, rhythm control with AADs did not significantly reduce the primary composite endpoint of all-cause mortality and HF hospitalization when compared with a pharmacological rate control strategy., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Reduced exercise capacity and exercise intolerance are commonly reported by individuals with atrial fibrillation (AF). Our objectives were to evaluate the contributing factors to reduced exercise capacity and describe the association between subjective measures of exercise intolerance versus objective measures of exercise capacity., Methods: Two hundred and three (203) patients with non-permanent AF and preserved ejection fraction undergoing cardiopulmonary exercise testing (CPET) were recruited. Clinical characteristics, AF-symptom evaluation, and transthoracic echocardiography measures were collected. Peak oxygen consumption (VO 2peak ) was calculated during CPET as an objective measure of exercise capacity. We assessed the impact of 16 pre-defined clinical features, comorbidities and cardiac functional parameters on VO 2peak ., Results: Across this cohort (Age 66±11 years, 40.4% female and 32% in AF), the mean VO 2peak was 20.3±6.3 mL/kg/min. 24.9% of patients had a VO 2peak considered low (<16 mL/kg/min). In multivariable analysis, echocardiography-derived estimates of elevated left ventricular (LV) filling pressure (E/E') and reduced chronotropic index were significantly associated with lower VO 2peak . The presence of AF at the time of testing was not significantly associated with VO 2peak but was associated with elevated minute ventilation to carbon dioxide production indicating impaired ventilatory efficiency. There was a poor association between VO 2peak and subjectively reported exercise intolerance and exertional dyspnoea., Conclusion: Reduced exercise capacity in AF patients is associated with elevated LV filling pressure and reduced chronotropic response rather than rhythm status. Subjectively reported exercise intolerance is not a sensitive assessment of reduced exercise capacity. These findings have important implications for understanding reduced exercise capacity amongst AF patients and the approach to management in this cohort. (ACTRN12619001343190)., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: This subanalysis of the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) trial aimed to address the association between atrial fibrillation (AF) recurrence, AF burden, and hard clinical outcomes in heart failure (HF) patients with AF., Background: The CASTLE-AF trial demonstrated the benefit of CA compared to pharmacological treatment in decreasing mortality and CV hospitalizations in patients with AF and HFrEF. However, the impact of AF recurrence and AF burden after ablation on long-term treatment benefit remains unknown., Methods: The CASTLE-AF protocol randomized 363 patients with coexisting HF and AF in a multicenter prospective controlled fashion to catheter ablation (n = 179) versus pharmacological therapy (n = 184). Two hundred eighty patients were included in this subanalysis (as-treated), 128 of them underwent ablation and 152 received pharmacological treatment. All patients had implanted dual chamber or biventricular implantable defibrillators with activated home monitoring capabilities. The individual AF burden was calculated as the percentage of the atrial arrhythmia time per day., Results: AF burden at baseline was not predictive of the primary endpoint (p = 0.473) or all-cause mortality (p = 0.446). AF recurrence (defined as any episode >30 s) did not show any relationship with the primary endpoints of mortality and occurrence of HF, irrespective of the treatment arm. An AF burden below 50% after 6 months of catheter ablation, was associated with a significant decrease in primary composite outcome (hazard ratio [HR]: 0.33; 95% confidence interval [CI]: 0.15 to 0.71; p = 0.014) and all-cause mortality (HR: 0.23; 95% CI: 0.07 to 0.71; p = 0.031). The risk of the primary endpoint or mortality was directly related to a low (<50%) or high (≥50%) AF burden at 6 months post-ablation., Conclusions: AF burden at 6 months was predictive of hard clinical outcomes in HF patients with AF. The first recurrent atrial tachyarrhythmia episode >30 s after ablation was not associated with improvement in mortality and hospitalization for HF. (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF [CASTLE-AF]; NCT00643188)., Competing Interests: Funding Support and Author Disclosures This study was funded by Biotronik. Dr. Brachmann has received consulting fees from Abbott, St. Jude Medical, Medtronic, Bayer, LivaNova, Pfizer, Boston Scientific, Boehringer Ingelheim, and Biotronik. Dr. Sohns has received modest lecture honoraria and congress sponsoring from Abbott, Biosense Webster, and Medtronic. Dr. Boersma has received consulting fees, paid to his institution, from Medtronic and Boston Scientific. Dr. Merkely has received grant support from Boston Scientific; and has received lecture fees from Medtronic, Biotronik, St. Jude Medical, and Terumo. Dr. Sanders has received grant support from St. Jude Medical, Boston Scientific, Biosense Webster, Biotronik, LivaNova, and Medtronic; has served on advisory boards for St. Jude Medical, Boston Scientific, Biosense Webster, CathRx, Biotronik, LivaNova, and Medtronic; and has received consulting fees from St. Jude Medical, Boston Scientific, and Medtronic. Dr. Bänsch has received consulting fees from Biotronik. Dr. Marrouche has received grant support and consulting fees from Abbott, Wavelet Health, Medtronic, Vytronus, Biosense Webster, Boston Scientific, GE Health Care, and Siemens; has received consulting fees from Preventice; and holds equity in Marrek and Cardiac Design. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The WiSE system is a novel, leadless endocardial system that can provide cardiac resynchronization therapy in patients who cannot be treated with a conventional epicardial left ventricular lead. Safety and efficacy were being evaluated in the pivotal, randomized, double-blind SOLVE-CRT Trial (Stimulation of the Left Ventricular Endocardium for Cardiac Resynchronization Therapy.) The trial was initiated in 2018; however, patient enrollment was significantly impacted by the COVID-19 pandemic necessitating a change in design. This article describes the revised trial and the scientific rationale for the specific changes in the protocol., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) and heart failure (HF) have similar risk factors, frequently coexist, and potentiate each other in a vicious cycle. Evidence suggests the presence of AF in both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) increases the risk of all-cause mortality and stroke, particularly when AF is incident. Catheter ablation may be an effective strategy in controlling symptoms and improving quality of life in AF-HFrEF. Strong data guiding management of AF-HFpEF are lacking largely due to its challenging diagnosis. Improving outcomes associated with these coexistent conditions requires further careful investigation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Traditional methods for the quantification of OSA severity may not encapsulate potential relationships between hypoxemia in OSA and cardiovascular risk., Research Question: Do novel nocturnal oxygen saturation (Spo 2 ) metrics have prognostic value in patients with OSA and high cardiovascular event risk?, Study Design and Methods: We conducted post hoc analyses of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial. In 2687 individuals, Cox proportional hazards models that were stratified for treatment allocation were used to determine the associations between clinical characteristics, pulse oximetry-derived metrics that were designed to quantify sustained and episodic features of hypoxemia, and cardiovascular outcomes. Metrics included oxygen desaturation index, time <90% Spo 2 , average Spo 2 for the entire recording (mean Spo 2 ), average Spo 2 during desaturation events (desaturation Spo 2 ), average baseline Spo 2 interpolated across episodic desaturation events (baseline Spo 2 ), episodic desaturation event duration and desaturation/resaturation-time ratio, and mean and SD of pulse rate., Results: Neither apnea-hypopnea index, oxygen desaturation index, nor any of the novel Spo 2 metrics were associated with the primary SAVE composite cardiovascular outcome. Mean and baseline Spo 2 were associated with heart failure (hazard ratio [HR], 0.81; 95% CI, 0.69-0.95; P = .009; and HR, 0.78; 95% CI, 0.67-0.90; P = .001, respectively) and myocardial infarction (HR, 0.86; 95% CI, 0.77-0.95; P = .003; and HR, 0.81; 95% CI, 0.73-0.90; P < .001, respectively). Desaturation duration and desaturation/resaturation time ratio, with established risk factors, predicted future heart failure (area under the curve, 0.86; 95% CI, 0.79-0.93)., Interpretation: Apnea-hypopnea index and oxygen desaturation index were not associated with cardiovascular outcomes. In contrast, the pattern of oxygen desaturation was associated with heart failure and myocardial infarction. However, concomitant risk factors remained the predominant determinants for secondary cardiovascular events and thus deserve the most intensive management., (Copyright © 2020. Published by Elsevier Inc.)

Background: Recent data demonstrate promising effects on left ventricular dysfunction and left ventricular ejection fraction (LVEF) improvement following ablation for atrial fibrillation (AF) in patients with heart failure. We sought to study the relationship between LVEF, New York Heart Association class on presentation, and the end points of mortality and heart failure admissions in the CASTLE-AF study (Catheter Ablation for Atrial Fibrillation With Heart Failure) population. Furthermore, predictors for LVEF improvement were examined., Methods: The CASTLE-AF patients with coexisting heart failure and AF (n=363) were randomized in a multicenter prospective controlled fashion to ablation (n=179) versus pharmacological therapy (n=184). Left ventricular function and New York Heart Association class were assessed at baseline (after randomization) and at each follow-up visit., Results: In the ablation arm, a significantly higher number of patients experienced an improvement in their LVEF to >35% at the end of the study (odds ratio, 2.17; P <0.001). Compared with the pharmacological therapy arm, both ablation patient groups with severe (<20%) or moderate/severe (≥20% and <35%) baseline LVEF had a significantly lower number of composite end points (hazard ratio [HR], 0.60; P =0.006), all-cause mortality (HR, 0.54; P =0.019), and cardiovascular hospitalizations (HR, 0.66; P =0.017). In the ablation group, New York Heart Association I/II patients at the time of treatment had the strongest improvement in clinical outcomes (primary end point: HR, 0.43; P <0.001; mortality: HR, 0.30; P =0.001)., Conclusions: Compared with pharmacological treatment, AF ablation was associated with a significant improvement in LVEF, independent from the severity of left ventricular dysfunction. AF ablation should be performed at early stages of the patient's heart failure symptoms.

A 72-year-old woman with a dual-chamber implantable cardioverter-defibrillator (Biotronik Lumax 540 DR-T) at elective replacement indicator presented for generator replacement. A new MicroPort generator (Platinium DR) was attached to her existing leads. Eight days later, multiple red alert messages were received on the Biotronik remote monitoring system from the explanted generator. Investigations revealed alert transmission via a CardioMessenger Smart mobile device registered to another patient that came into proximity of the explanted generator. The Biotronik remote monitoring system is unique in that red alerts could be sent through any CardioMessenger Smart device regardless of whether they were paired., Competing Interests: Declaration of Competing Interest Dr. Sanders reports having served on the advisory board of Biosense-Webster, Medtronic, Abbott Medical, Boston Scientific and CathRx. Dr. Sanders reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Biosense-Webster, Medtronic, Abbott Medical and Boston Scientific. Dr. Sanders reports that the University of Adelaide has received on his behalf research funding from Medtronic, Abbott Medical, Boston Scientific, Biotronik and MicroPort. Dr. Lau reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Abbott Medical, Bayer, Biotronik, Boehringer Ingelheim, Medtronic, MicroPort and Pfizer. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The aim of the meta-analysis was to determine the association of obesity and heart failure (HF) and the cardiac impact of intentional weight loss following bariatric surgery on cardiac structure and myocardial function in obese subjects., Methods: MEDLINE, Embase and Web of Science were searched up to 3 April 2018. Studies reporting association and prognostic impact of obesity in HF and the impact of intentional weight loss following bariatric surgery on cardiac structure and myocardial function in obesity were included in the meta-analysis., Results: 4959 citations were reviewed. After exclusions, 29 studies were analysed. A 'J curve' relationship was observed between body mass index (BMI) and risk of HF with maximum risk in the morbidly obese (1.73 (95% CI 1.30 to 2.31), p<0.001, n=11). Although 'obesity paradox' was observed for all-cause mortality, the overweight group was associated with lower cardiovascular (CV) mortality (OR=0.86 (95% CI 0.79 to 0.94), n=11) with no significant differences across other BMI groups. Intentional weight loss induced by bariatric surgery in obese patients (n=9) without established HF, atrial fibrillation or known coronary artery disease, was associated with a reduction in left ventricular mass index (p<0.0001), improvement in left ventricular diastolic function (p≤0.0001) and a reduction in left atrial size (p=0.02)., Conclusions: Despite the increased risk of HF with obesity, an 'obesity paradox' is observed for all-cause mortality. However, the nadir for CV mortality is observed in the overweight group. Importantly, intentional weight loss was associated with improvement in indices of cardiac structure and myocardial function in obese patients., Trial Registration Number: APP 74412., Competing Interests: Competing interests: The University of Adelaide reports receiving on behalf of RM lecture and/or consulting fees from Abbott and Medtronic. The University of Adelaide reports receiving on behalf of RM research funding from Abbott and Medtronic. DL reports having served on the advisory board of LivaNova and Medtronic. The University of Adelaide reports receiving on behalf of DL reports lecture and/or consulting fees from LivaNova, Medtronic, Pfizer and ResMed. The University of Adelaide reports receiving on behalf of DL research funding from Sanofi, ResMed and Medtronic. PS reports having served on the advisory board of Biosense-Webster, Medtronic, Abbott, Boston Scientific and CathRx. The University of Adelaide reports receiving on behalf of PS lecture and/or consulting fees from Biosense-Webster, Medtronic, Abbott and Boston Scientific. The University of Adelaide reports receiving on behalf of PS research funding from Medtronic, Abbott, Boston Scientific, Biotronik and Liva Nova., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study is to characterise hospitalisations due to atrial fibrillation (AF) compared with two other common cardiovascular conditions, myocardial infarction (MI) and heart failure (HF), in addition to the associated economic burden of these hospitalisations and contribution of AF-related procedures., Methods: The primary outcome measure was the rate of increase of AF, MI and HF hospitalisations from 1993 to 2013. The rate of increase of AF-related procedures including cardioversion and ablation were also collected, in addition to direct costs associated with hospitalisations for each of these three conditions., Results: AF hospitalisations increased 295% over the 21-year period to a total of 61 424 in 2013. In comparison, MI and HF hospitalisations increased by only 73% and 39%, respectively, over the same period. Considering population changes, there was an annual increase in AF hospitalisations of 5.2% (incidence rate ratio [IRR] 1.052; 95% CI 1.046 to 1.059; p<0.001). In contrast, there was a 2.2% increase per annum for MI (IRR 1.022; 95% CI 1.017 to 1.027; p<0.001) and negligible annual change for HF hospitalisations (IRR 1.000; 95% CI 0.997 to 1.002; p=0.78). Cardioversion and AF ablation increased by 10% and 26% annually, respectively. AF hospitalisation costs rose by 479% over the 21-year period, an increase that was more than double that of MI and HF., Conclusions: The burden of AF hospitalisations continues to rise unabated. AF has now surpassed both MI and HF hospitalisations and represents a growing cost burden. New models of healthcare delivery are required to stem this growing healthcare burden., Competing Interests: Competing interests: PS reports having served on the advisory board of Biosense-Webster, Medtronic, St Jude Medical, Boston Scientific and CathRx. PS reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Biosense-Webster, Medtronic, St Jude Medical and Boston Scientific. PS reports that the University of Adelaide has received on his behalf research funding from Medtronic, St Jude Medical, Boston Scientific, Biotronik and LivaNova. CXW reports that the University of Adelaide has received on his behalf lecture, travel and/or research funding from Novartis, Servier, Boehringer-Ingelheim and Medtronic., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Catheter ablation (CA) is highly efficacious for symptomatic atrial fibrillation (AF) but data predominantly comes from patients with preserved ventricular function. We performed an updated systematic review and meta-analysis of randomised controlled trials (RCT) comparing CA versus medical therapy for AF associated with heart failure (HF)., Methods: Medline, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for RCTs reporting clinical outcomes of CA versus medical therapy for AF in HF patients with ≥6 months' follow-up (atrioventricular-node ablation/device therapy studies excluded). Primary endpoint was change in left ventricular ejection fraction (LVEF). Secondary endpoints were 6-minute walk test (6MWT) distance, quality of life (QoL; measured by the Minnesota Living with Heart Failure Questionnaire [MLHFQ]), peri-procedural mortality, major peri-procedural complications and mid-term (≥1-year) survival., Results: Six RCTs (n=772 patients; mean age 62±11years, LVEF 30±9%) were included. Catheter ablation, compared to medical therapy was associated with: greater improvement in LVEF (mean difference [MD] 5.67%; 95% Confidence Interval [CI], 3-8; I 2 =87%; p<0.001), greater increase in 6MWT distance (MD 25.1 metres; 95% CI, 0.6-50; I 2 =94%; p=0.04), improved QoL with greater reduction in MLHFQ scores (MD 9.03; 95% CI, 2.5-15.6; I 2 =47%; p=0.007), and significantly reduced mid-term mortality (relative risk 0.52; 95% CI, 0.4-0.8; I 2 =0%; p=0.001). Freedom from AF after ≥1 procedure was 71%; major complications occurred in 8% of patients., Conclusion: Catheter ablation is superior to medical therapy for AF in patients with heart failure resulting in greater improvement in LVEF, quality of life and functional status, with a survival benefit., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Atrial fibrillation (AF) and heart failure (HF) pose international health care challenges that contribute significantly to hospitalizations, morbidity, mortality, and significant health care costs. Both AF and HF contribute to the development of each other and both are associated with a worsened prognosis when they occur together. Assessment of systolic function via transthoracic echocardiography is essential in the investigation of the AF patient. Clinical and echocardiographic assessment may classify AF patients with HF into HF with reduced ejection fraction (HF-rEF) and HF with preserved ejection fraction (HF-pEF). Such classification can assist in numerous important management decisions in AF., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Background: Battery longevity is an important factor that may influence the selection of cardiac implantable electronic devices (CIEDs). However, there remains a lack of industry-wide standardized reporting of predicted CIED longevity to facilitate informed decision-making for implanting physicians and payers., Objective: The purpose of this study was to compare the predicted longevity of current generation CIEDs using best-matched CIEDs settings to assess differences between brands and models., Methods: Data were extracted for current model pacemakers, implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy-defibrillators (CRT-Ds) from product manuals and, where absent, by communication with the manufacturers. Pacemaker longevity estimations were based on standardized pacing outputs (2.5V, 0.40-ms pulse width, 500-Ω impedance) and pacing loads of 50% or 100% at 60 bpm. ICD and CRT-D longevity were estimated at 0% pacing and 15% atrial plus 100% biventricular pacing, with essential capacitor reforms and zero clinical shocks., Results: Mean maximum predicted longevity of single- and dual-chamber pacemakers was 12.0 ± 2.1 and 9.8 ± 1.9 years, respectively. Use of advanced features such as remote monitoring, prearrhythmia electrogram storage, and rate response can result in ∼1.4 years of reduction in longevity. Mean maximum predicted longevity of ICDs and CRT-Ds was 12.4 ± 3.0 and 8.8 ± 2.1 years, respectively. Of note, there were significant variations in predicted CIED longevity according to device manufacturers, with up to 44%, 42%, and 44% difference for pacemakers, ICDs, and CRT-Ds, respectively., Conclusion: Contemporary CIEDs demonstrate highly variable predicted longevity according to device manufacturers. This may impact on health care costs and long-term clinical outcomes., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Mortality and morbidity are higher among patients with atrial fibrillation and heart failure than among those with heart failure alone. Catheter ablation for atrial fibrillation has been proposed as a means of improving outcomes among patients with heart failure who are otherwise receiving appropriate treatment., Methods: We randomly assigned patients with symptomatic paroxysmal or persistent atrial fibrillation who did not have a response to antiarrhythmic drugs, had unacceptable side effects, or were unwilling to take these drugs to undergo either catheter ablation (179 patients) or medical therapy (rate or rhythm control) (184 patients) for atrial fibrillation in addition to guidelines-based therapy for heart failure. All the patients had New York Heart Association class II, III, or IV heart failure, a left ventricular ejection fraction of 35% or less, and an implanted defibrillator. The primary end point was a composite of death from any cause or hospitalization for worsening heart failure., Results: After a median follow-up of 37.8 months, the primary composite end point occurred in significantly fewer patients in the ablation group than in the medical-therapy group (51 patients [28.5%] vs. 82 patients [44.6%]; hazard ratio, 0.62; 95% confidence interval [CI], 0.43 to 0.87; P=0.007). Significantly fewer patients in the ablation group died from any cause (24 [13.4%] vs. 46 [25.0%]; hazard ratio, 0.53; 95% CI, 0.32 to 0.86; P=0.01), were hospitalized for worsening heart failure (37 [20.7%] vs. 66 [35.9%]; hazard ratio, 0.56; 95% CI, 0.37 to 0.83; P=0.004), or died from cardiovascular causes (20 [11.2%] vs. 41 [22.3%]; hazard ratio, 0.49; 95% CI, 0.29 to 0.84; P=0.009)., Conclusions: Catheter ablation for atrial fibrillation in patients with heart failure was associated with a significantly lower rate of a composite end point of death from any cause or hospitalization for worsening heart failure than was medical therapy. (Funded by Biotronik; CASTLE-AF ClinicalTrials.gov number, NCT00643188 .).

Congestive Heart Failure (CHF) is an ambulatory care sensitive condition, associated with significant morbidity and mortality, rarely with cure. Outpatient based pharmacological management represents the main and most important aspect of care, and is usually lifelong. This narrative styled opinion review looks at the pharmacological agents recommended in the guidelines in context of the Northern Territory (NT) of Australia. We explore the concept of validity, a term used to describe the basis of standardising a particular trial or study and the population to which it is applicable. We aim to highlight the problems of the current guidelines based approach. We also present alternatives that could utilise the core principles from major trials, while incorporating regional considerations, which could benefit clients living in the NT and remote Australia., (Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

QT variability (QTV) signifies repolarization lability, and increased QTV is a risk predictor for sudden cardiac death. The aim of the present study was to investigate the role of autonomic nervous system activity on QTV. This study was performed in 29 subjects: 10 heart failure (HF) patients with spontaneous ventricular tachycardia [HFVT(+)], 10 HF patients without spontaneous VT [HFVT(-)], and 9 subjects with structurally normal hearts (HNorm). The beat-to-beat QT interval was measured on 3-min records of surface ECGs at baseline and during interventions (atrial pacing and esmolol, isoprenaline, and atropine infusion). Variability in QT intervals was expressed as the SD of all QT intervals (SDQT). The ratio of the SDQT to SD of RR intervals (SDRR) was calculated as an index of QTV normalized to heart rate variability. There was a trend toward a higher baseline SDQT-to-SDRR ratio in the HFVT(+) group compared with the HFVT(-) and HNorm groups (P = 0.09). SDQT increased significantly in the HFVT(+) and HFVT(-) groups compared with the HNorm group during fixed-rate atrial pacing (P = 0.008). Compared with baseline, isoprenaline infusion increased SDQT in HNorm subjects (P = 0.02) but not in HF patients. SDQT remained elevated in the HFVT(+) group relative to the HNorm group despite acute β-adrenoceptor blockade with esmolol (P = 0.02). In conclusion, patients with HF and spontaneous VT have larger fluctuations in beat-to-beat QT intervals. This appears to be a genuine effect that is not solely a consequence of heart rate variation. The effect of acute autonomic nervous system modulation on QTV appears to be limited in HF patients.

Objectives: The aim of this study was to systematically review the medical literature to evaluate the impact of AV nodal ablation in patients with heart failure and coexistent atrial fibrillation (AF) receiving cardiac resynchronization therapy (CRT)., Background: CRT has a substantial evidence base in patients in sinus rhythm with significant systolic dysfunction, symptomatic heart failure, and prolonged QRS duration. The role of CRT is less well established in AF patients with coexistent heart failure. AV nodal ablation has recently been suggested to improve outcomes in this group., Methods: Electronic databases and reference lists through September 15, 2010, were searched. Two reviewers independently evaluated citation titles, abstracts, and articles. Studies reporting the outcomes after AV nodal ablation in patients with AF undergoing CRT for symptomatic heart failure and left ventricular dyssynchrony were selected. Data were extracted from 6 studies, including 768 CRT-AF patients, composed of 339 patients who underwent AV nodal ablation and 429 treated with medical therapy aimed at rate control alone., Results: AV nodal ablation in CRT-AF patients was associated with significant reductions in all-cause mortality (risk ratio: 0.42 [95% confidence interval: 0.26 to 0.68]), cardiovascular mortality (risk ratio: 0.44 [95% confidence interval: 0.24 to 0.81]), and improvement in mean New York Heart Association functional class (risk ratio: -0.52 [95% confidence interval: -0.87 to -0.17])., Conclusions: AV nodal ablation was associated with a substantial reduction in all-cause mortality and cardiovascular mortality and with improvements in New York Heart Association functional class compared with medical therapy in CRT-AF patients. Randomized controlled trials are warranted to confirm the efficacy and safety of AV nodal ablation in this patient population., (© 2012 American College of Cardiology Foundation.)

Background: It has been suggested that omega-3 polyunsaturated fatty acids (n-3 PUFAs) may prevent the development of atrial fibrillation (AF)., Objective: The purpose of this study was to evaluate the impact of these agents on development of the AF substrate in heart failure (HF)., Methods: In this study, HF was induced by intracoronary doxorubicin infusions. Twenty-one sheep [7 with n-3 PUFAs treated HF (HF-PUFA), 7 with olive oil-treated HF controls (HF-CTL), 7 controls (CTL)] were studied. Open chest electrophysiologic study was performed with assessment of biatrial effective refractory period (ERP) and conduction. Cardiac function was monitored by magnetic resonance imaging. Atrial n-3 PUFAs levels were quantified using chromatography. Structural analysis was also performed., Results: Atrial n-3 PUFAs levels were twofold to threefold higher in the HF-PUFA group. n-3 PUFAs prevented the development of HF-related left atrial enlargement (P = .001) but not left ventricular/atrial dysfunction. Atrial ERP was significantly lower in the HF-PUFA group (P <.001), but ERP heterogeneity was unchanged. In addition, n-3 PUFAs suppressed atrial conduction abnormalities seen in HF of prolonged P-wave duration (P = .01) and slowed (P <.001) and heterogeneous (P <.05) conduction. The duration of induced AF episodes in HF-PUFA was shorter (P = .02), although AF inducibility was unaltered (P = NS). A 20% reduction of atrial interstitial fibrosis was seen in the HF-PUFA group (P <.05)., Conclusion: In this ovine HF study, chronic n-3 PUFAs use protected against adverse atrial remodeling by preventing atrial enlargement, fibrosis, and conduction abnormalities leading to shorter AF episodes despite lower ERP., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

Introduction: All preclinical studies of atrial remodeling in heart failure (HF) have been confined to a single model of rapid ventricular pacing. To evaluate whether the atrial changes were specific to the model or represented an end result of HF, this study aimed to characterize atrial remodeling in an ovine model of doxorubicin-induced cardiomyopathy., Methods and Results: Fourteen sheep, 7 with cardiomyopathy induced by repeated intracoronary doxorubicin infusions and 7 controls, were studied. The development of HF was monitored by cardiac imaging and hemodynamic parameters. Open chest electrophysiological study was performed using custom-made 128-electrode epicardial plaque assessing effective refractory period (ERP) and conduction velocity. Atrial tissues were harvested for structural analysis. The HF group had demonstrable moderate global HF (left ventricular ejection fraction [LVEF]: 37.1 vs 46.4%; P = 0.003) and showed the following compared to controls: left atrial dilatation (P = 0.02) and dysfunction (P = 0.005); longer P-wave duration (P < 0.05); higher ERP at all cycle lengths (P ≤ 0.002) and locations (P < 0.001); slower conduction velocity (P < 0.001); increased conduction heterogeneity index (P < 0.001); increased atrial fibrosis (right atrial [RA]: 5.9 ± 2.6 vs 2.8 ± 0.9%; P < 0.0001, left atrial [LA]: 3.7 ± 2.2 vs 2.4 ± 1.1%; P = 0.002), and longer induced atrial fibrillation (AF) episodes (16 ± 22 vs 2 ± 3 seconds; P = 0.04)., Conclusion: In this model of HF, there was significant atrial remodeling characterized by atrial enlargement/dysfunction, increased fibrosis, slowed/heterogeneous conduction, and increased refractoriness associated with more sustained AF. These findings appear the "same sort" to previous models of HF implicating a final common substrate leading to the development of AF in HF., (© 2010 Wiley Periodicals, Inc.)

Background: Congestive heart failure and atrial fibrillation often coexist, and each adversely affects the other with respect to management and prognosis. We prospectively evaluated the effect of catheter ablation for atrial fibrillation on left ventricular function in patients with heart failure., Methods: We studied 58 consecutive patients with congestive heart failure and a left ventricular ejection fraction of less than 45 percent who were undergoing catheter ablation for atrial fibrillation. We selected as controls 58 patients without congestive heart failure who were undergoing ablation for atrial fibrillation, matched according to age, sex, and classification of atrial fibrillation. We evaluated the patients' left ventricular function and dimensions, symptom score, exercise capacity, and quality of life at baseline and at months 1, 3, 6, and 12., Results: After a mean (+/-SD) of 12+/-7 months, 78 percent of the patients with congestive heart failure and 84 percent of the controls remained in sinus rhythm (P=0.34) (69 percent and 71 percent, respectively, were in sinus rhythm without the administration of antiarrhythmic drugs). The patients with congestive heart failure had significant improvement in left ventricular function (increases in the ejection fraction and fractional shortening of 21+/-13 percent and 11+/-7 percent, respectively; P<0.001 for both comparisons), left ventricular dimensions (decreases in the diastolic and systolic diameters of 6+/-6 mm and 8+/-7 mm, respectively; P=0.03 and P<0.001, respectively), exercise capacity, symptoms, and quality of life. The ejection fraction improved significantly not only in patients without concurrent structural heart disease (24+/-10 percent, P<0.001) and those with inadequate rate control before ablation (23+/-10 percent, P<0.001), but also in those with coexisting heart disease (16+/-14 percent, P<0.001) and adequate rate control before ablation (17+/-15 percent, P<0.001)., Conclusions: Restoration and maintenance of sinus rhythm by catheter ablation without the use of drugs in patients with congestive heart failure and atrial fibrillation significantly improve cardiac function, symptoms, exercise capacity, and quality of life., (Copyright 2004 Massachusetts Medical Society.)

Introduction: We conducted an acute echocardiographic study comparing hemodynamic and ventricular dyssynchrony parameters during left ventricular pacing (LVP) and biventricular pacing (BVP). We sought to clarify the mechanisms responsible for similar hemodynamic improvement despite differences in electrical activation., Methods and Results: Thirty-three patients underwent echocardiography prior to implantation with a multisite pacing device (spontaneous rhythm [SR]) and 2 days after implantation (BVP and LVP). Interventricular dyssynchrony (pulsed-wave Doppler), extent of myocardium displaying delayed longitudinal contraction (%DLC; tissue tracking), and index of LV dyssynchrony (pulsed-wave tissue Doppler imaging) were assessed. Compared to SR, BVP and LVP caused similar significant improvement of cardiac output (LVP: 3.2 +/- 0.5, BVP: 3.1 +/- 0.7, SR: 2.3 +/- 0.6 L/min; P < 0.01) and mitral regurgitation (LVP: 25.1 +/- 10, BVP: 24.7 +/- 11, baseline: 37.9 +/- 14% jet area/left atria area; P < 0.01). LVP resulted in a smaller index of LV dyssynchrony than BVP (29 +/- 10 vs 34 +/- 14; P < 0.05). However, LVP exhibited a longer aortic preejection delay (220 +/- 34 vs 186 +/- 28 msec; P < 0.01), longer LV electromechanical delays (244.5 +/- 39 vs 209.5 +/- 47 msec; P < 0.05), greater interventricular dyssynchrony (56.6 +/- 18 vs 31.4 +/- 18; P < 0.01), and higher%DLC (40.1 +/- 08 vs 30.3 +/- 09; P < 0.05), leading to shorter LV filling time (387 +/- 54 vs 348 +/- 44 msec; P < 0.05) compared to BVP., Conclusion: Although LVP and BVP provide similar hemodynamic improvement, LVP results in more homogeneous but substantially delayed LV contraction, leading to shortened filling time and less reduction in postsystolic contraction. These data may influence the choice of individual optimal pacing configuration.

Background: Experimental and clinical studies have demonstrated diffuse atrial remodeling in congestive heart failure (CHF). We hypothesized that patients with CHF would demonstrate derangement of sinus node function., Methods and Results: Eighteen patients with symptomatic CHF (left ventricular ejection fraction, 26+/-5%) and 18 age-matched control subjects were studied. Under autonomic blockade, the following were evaluated: intrinsic sinus cycle length, corrected sinus node recovery time (CSNRT), sinoatrial conduction time, number and duration of fractionated electograms or double potentials along the crista terminalis, and location of the earliest sinus activity. Electroanatomic mapping was performed to evaluate the location and nature of the sinus node complex, to characterize sinoatrial propagation, and to evaluate conduction abnormalities and voltage amplitude along the crista terminalis. Patients with CHF demonstrated the following findings compared with age-matched control subjects: prolongation of the intrinsic sinus cycle length (P=0.005), prolongation of CSNRT (P<0.0001), caudal localization of sinus activity both during sinus rhythm (P=0.03) and after pacing (P=0.002), prolongation of sinoatrial conduction time (P=0.02), greater number (P<0.0001) and duration (P<0.0001) of fractionated electrograms or double potentials along the crista terminalis, loss of voltage amplitude along the crista terminalis (P=0.02), and abnormal and circuitous propagation of the sinus impulse., Conclusions: This study demonstrates that patients with CHF have significant sinus node remodeling characterized by anatomic and structural changes along the crista terminalis with a reduction in functional sinus node reserve. This finding may have implications for the development of clinical bradycardia in CHF and for the use of negatively chronotropic agents and pacing in this condition.

Background: Atrial fibrillation (AF) frequently complicates congestive heart failure (CHF). However, the electrophysiological substrate for AF in humans with CHF remains unknown. We evaluated the electrophysiological and electroanatomic characteristics of the atria in patients with CHF., Methods and Results: Twenty-one patients (aged 53.7+/-13.6 years) with symptomatic CHF (left ventricular ejection fraction 25.5+/-6.0%) and 21 age-matched controls were studied. The following were evaluated: effective refractory periods (ERPs) from the high and low lateral right atrium (LRA), high septal right atrium, and distal coronary sinus (CS); conduction time along the CS and LRA; corrected sinus node recovery times; P-wave duration; and conduction at the crista terminalis. In a subset, electroanatomic mapping was performed to determine atrial activation, regional conduction velocity, double potentials, fractionated electrograms, regional voltage, and areas of electrical silence. Patients with CHF demonstrated an increase in atrial ERP with no change in the heterogeneity of refractoriness, an increase of atrial conduction time along the LRA and the CS, prolongation of the P-wave duration and corrected sinus node recovery times, and greater number and duration of double potentials along the crista terminalis. Electroanatomic mapping demonstrated regional conduction slowing with a greater number of electrograms with fractionation or double potentials, associated with areas of low voltage and electrical silence (scar). Patients with CHF demonstrated an increased propensity for AF with single extrastimuli, and induced AF was more often sustained., Conclusions: Atrial remodeling due to CHF is characterized by structural changes, abnormalities of conduction, sinus node dysfunction, and increased refractoriness. These abnormalities may be responsible in part for the increased propensity for AF in CHF.

AIM: The 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Patients With Atrial Fibrillation provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation. METHODS: A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation and the 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.

Background and Aims Atrial fibrillation (AF) is a chronic progressive disorder. Persistent forms of AF are associated with increased rates of thromboembolism, heart failure, and death. Catheter ablation modifies the pathogenic mechanism of AF progression. No randomized studies have evaluated the impact of the ablation energy on progression to persistent atrial tachyarrhythmia. Methods Three hundred forty-six patients with drug-refractory paroxysmal AF were enrolled and randomly assigned to contact-force–guided RF ablation (CF-RF ablation, 115), 4 min cryoballoon ablation (CRYO-4, 115), or 2 min cryoballoon ablation (CRYO-2, 116). Implantable cardiac monitors placed at study entry were used for follow-up. The main outcome was the first episode of persistent atrial tachyarrhythmia. Secondary outcomes included atrial tachyarrhythmia recurrence and arrhythmia burden on the implantable monitor. Results At a median of 944.0 (interquartile range [IQR], 612.5–1104) days, 0 of 115 patients (0.0%) randomly assigned to CF-RF, 8 of 115 patients (7.0%) assigned to CRYO-4, and 5 of 116 patients (4.3%) assigned to CRYO-2 experienced an episode of persistent atrial tachyarrhythmia (P =.03). A documented recurrence of any atrial tachyarrhythmia ≥30 s occurred in 56.5%, 53.9%, and 62.9% of those randomized to CF-RF, CRYO-4, and CRYO-2, respectively; P =.65. Compared with that of the pre-ablation monitoring period, AF burden was reduced by a median of 99.5% (IQR 94.0%, 100.0%) with CF-RF, 99.9% (IQR 93.3%–100.0%) with CRYO-4, and 99.1%% (IQR 87.0%–100.0%) with CRYO-2 (P =.38). Conclusions Catheter ablation of paroxysmal AF using radiofrequency energy was associated with fewer patients developing persistent AF on follow-up. [ABSTRACT FROM AUTHOR]

Although cardiac resynchronization therapy (CRT) is an established therapy in selected patients with heart failure with reduced ejection fraction (HFrEF), its role in orthotopic heart transplant (OHT) recipients remains understudied. We describe a case of successful CRT implantation in an OHT recipient for HFrEF and high-grade atrioventricular block. This case highlights the deliberations made given the lack of clinical trial and observational evidence for this therapy in OHT recipients. This case demonstrates the feasibility of cardiac resynchronization therapy (CRT) in an orthotopic heart transplant (OHT) recipient and adds to the scarcely reported data on the utility of CRT in this population. Given the exclusion of OHT recipients from the major CRT trials, further research is required to refine the indications for CRT implantation in this population. [ABSTRACT FROM AUTHOR]

Management of atrial fibrillation (AF) requires a comprehensive approach due to the limited success of medical or procedural approaches in isolation. Multiple modifiable risk factors contribute to the development and progression of the underlying substrate, with a heightened risk of progression evident with inadequate risk factor management. With increased mortality, stroke, heart failure and healthcare utilisation linked to AF, international guidelines now strongly support risk factor modification as a critical pillar of AF care due to evidence demonstrating the efficacy of this approach. Effective lifestyle management is key to arrest and reverse the progression of AF, in addition to increasing the likelihood of freedom from arrhythmia following catheter ablation. [ABSTRACT FROM AUTHOR]

Abstract Background Atrial fibrillation is a serious public health problem posing a considerable burden to not only patients, but the healthcare environment due to high rates of morbidity, mortality, and medical resource utilization. There are limited data on the variation in treatment practice patterns across different countries, healthcare settings and the associated health outcomes. Methods/design RHYTHM-AF was a prospective observational multinational study of management of recent onset atrial fibrillation patients considered for cardioversion designed to collect data on international treatment patterns and short term outcomes related to cardioversion. We present data collected in 10 countries between May 2010 and June 2011. Enrollment was ongoing in Italy and Brazil at the time of data analysis. Data were collected at the time of atrial fibrillation episode in all countries (Australia, Brazil, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom), and cumulative follow-up data were collected at day 60 (±10) in all but Spain. Information on center characteristics, enrollment data, patient demographics, detail of atrial fibrillation episode, medical history, diagnostic procedures, acute treatment of atrial fibrillation, discharge information and the follow-up data on major events and rehospitalizations up to day 60 were collected. Discussion A total of 3940 patients were enrolled from 175 acute care centers. 70.5% of the centers were either academic (44%) or teaching (26%) hospitals with an overall median capacity of 510 beds. The sites were mostly specialized with anticoagulation clinics (65.9%), heart failure (75.1%) and hypertension clinics (60.1%) available. The RHYTHM-AF registry will provide insight into regional variability of antiarrhythmic and antithrombotic treatment of atrial fibrillation, the appropriateness of such treatments with respect to outcomes, and their cost-efficacy. Observations will help inform strategies to improve cardiovascular outcomes in patients with atrial fibrillation. Trial registration Clinical trials NCT01119716

The management of atrial fibrillation (AF) has focused on anticoagulation, rhythm control and ventricular rate control. Recently, a fourth pillar of AF management has been incorporated recognising the importance of risk factor management (RFM). There are several risk factors that contribute to the development and progression of AF, these include traditional risk factors such as age, hypertension, heart failure, diabetes and valvular heart disease. However, increasingly it is recognised that obesity, sleep apnoea, hyperlipidaemia, smoking, alcohol, physical inactivity, genetics, aortic stiffness are associated with the development of AF. Importantly, several of these risk factors are modifiable. We have seen the evolution of RFM programmes which have demonstrated promising results. Indeed, the evidence is now so compelling that major clinical guidelines strongly advocate that aggressive treatment of these risk factors as a key component of AF management. Patients with AF who comprehensively managed their risk factors demonstrate greater reduction in symptoms, AF burden, more successful ablations and improved outcomes with greater AF freedom. In this article, we will review the evidence for the association between cardiac risk factors and AF and assess the burgeoning evidence for improved AF outcomes associated with aggressive cardiac RFM. [ABSTRACT FROM AUTHOR]