Author + information
- Received March 22, 2017
- Revision received August 24, 2017
- Accepted August 28, 2017
- Published online January 15, 2018.
- Sandeep Prabhu, MBBSa,b,c,d,
- Aleksandr Voskoboinik, MBBSa,b,c,d,
- Alex J.A. McLellan, MBBS, PhDa,b,c,d,
- Kah Y. Peck, MBBSa,
- Bhupesh Pathik, MBBSc,d,
- Chrishan J. Nalliah, MBBSc,d,
- Geoff R. Wong, MBBSc,d,
- Sonia M. Azzopardi, CC Bc RNa,b,
- Geoffrey Lee, MBChB, PhDc,
- Justin Mariani, MBBS, PhDa,b,
- Liang-Han Ling, MBBS, PhDa,b,c,d,
- Andrew J. Taylor, MBBS, PhDa,b,
- Jonathan M. Kalman, MBBS, PhDc,d and
- Peter M. Kistler, MBBS, PhDa,b,d,∗ ()
- aDepartment of Cardiology, Alfred Hospital, Victoria, Australia
- bBaker IDI Heart and Diabetes Institute, Victoria, Australia
- cCardiology Department, Royal Melbourne Hospital, Victoria, Australia
- dFaculty of Medicine, Dentistry, and Health Sciences, University of Melbourne, Victoria, Australia
- ↵∗Address for correspondence:
Prof. Peter M. Kistler, Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, Victoria 3004, Australia.
Objectives This study sought to characterize the biatrial substrate in heart failure (HF) and persistent atrial fibrillation (PeAF).
Background Atrial fibrillation (AF) and HF frequently coexist; however, the contribution of HF to the biatrial substrate in PeAF is unclear.
Methods Consecutive patients with PeAF and normal left ventricular (NLV) systolic function (left ventricular ejection fraction [LVEF] >55%) or idiopathic cardiomyopathy (LVEF ≤45%) undergoing AF ablation were enrolled. In AF, pulmonary vein (PV) cycle length (PVCL) was recorded via a multipolar catheter in each PV and in the left atrial appendage for 100 consecutive cycles. After electrical cardioversion, biatrial electroanatomic mapping was performed. Complex electrograms, voltage, scarring, and conduction velocity were assessed.
Results Forty patients, 20 patients with HF (mean age: 62 ± 8.9 years; AF duration: 15 ± 11 months; LVEF: 33 ± 8.4%) and 20 with NLV (mean age: 59 ± 6.7 years; AF duration: 14 ± 9.1 months; p = 0.69; mean LVEF: 61 ± 3.6%; p < 0.001), were enrolled. HF reduced biatrial tissue voltage (p < 0.001) with greater voltage heterogeneity (p < 0.001). HF was associated with significantly more biatrial fractionation (left atrium [LA]: 30% vs. 9%; p < 0.001; right atrium [RA]: 28% vs. 11%; p < 0.001), low voltage (<0.5 mV) (LA: 23% vs. 6%; p = 0.002; RA: 20% vs 11%; p = 0.006), and scarring (<0.05 mV) in the LA (p = 0.005). HF was associated with a slower average PVCL (185 vs. 164 ms; p = 0.016), which correlated significantly with PV antral bipolar voltage (R = −0.62; p < 0.001) and fractionation (R = 0.46; p = 0.001).
Conclusions HF is associated with significantly reduced biatrial tissue voltage, fractionation, and prolongation of PVCL. Advanced biatrial remodeling may have implications for invasive and noninvasive rhythm control strategies in patients with AF and HF.
Atrial fibrillation (AF) and heart failure (HF) are burgeoning epidemics contributing to significant morbidity and mortality and an increasing burden on health care systems (1,2). AF and HF coexist in a significant proportion of patients due to significant overlap in the pathophysiological processes driving both conditions (3). Recently, catheter ablation for AF has been purported as an effective treatment for selected patients with AF and HF, with improvements in left ventricular (LV) function and functional class (4–6). However, the success of ablation is inferior in patients with HF compared to those with normal left ventricular (NLV) function (7,8). AF and HF are both associated with atrial structural remodeling, which adversely affects long-term outcomes after catheter ablation. However, within the persistent AF population, the specific contribution of LV systolic dysfunction to atrial remodeling, over and above the contribution of persistent AF itself, has not been determined. We sought to characterize structural remodeling in patients with persistent AF, with and without LV systolic dysfunction, using comprehensive detailed biatrial electroanatomic mapping.
Consecutive patients from 2 Australian centers undergoing catheter ablation for persistent AF were prospectively screened. Patients were included in the study if they were >18 years, had symptomatic persistent AF of at least 3 months’ duration, and had systolic left ventricular ejection fraction (LVEF) ≤45% (HF group) or ≥55% (NLV group) on pre-procedural cardiac imaging (either echocardiography or cardiac magnetic resonance [CMR]). Patients were excluded if they had paroxysmal AF or a known structural cause of HF such as previous myocardial infarction or severe valvular disease, had LVEF between 45% and 55%, or were unable to maintain sinus rhythm after electrical cardioversion to facilitate mapping. Persistent AF for this study was defined as AF duration >3 months to allow the assessment of pulmonary vein (PV) cycle length (PVCL) without the risks of spontaneous reversion. Long-standing persistent AF was defined as continuous AF duration for >1 year. All patients were adequately rate controlled for a minimum of 4 weeks before mapping and ablation. The study was approved by the human ethics committee at each study location.
Antiarrhythmic drugs were discontinued 5 half-lives before the procedure. Anticoagulation was stopped 2 to 5 days before ablation or continued (in the case of vitamin K antagonists) at the operator’s discretion, with intravenous heparin used intraprocedurally aiming for activated clotting time >350 s. After transesophageal echocardiography to exclude intracardiac thrombus, double transseptal access was performed. Left atrial (LA) geometry was constructed using a 20-pole lasso catheter (Biosense Webster Inc., Diamond Bar, California) and registered with the pre-procedural computed tomography or CMR. In AF, PVCL was recorded in each PV and in the left atrial appendage (LAA) as described in the “Pulmonary Vein Cycle Length” paragraph. Electrical cardioversion to sinus rhythm was then performed. Mapping was performed before ablation using the CARTO3 electroanatomic mapping system (Biosense Webster Inc.) during pacing from the coronary sinus at 600 ms with a 3.5-mm irrigated ablation catheter (Biosense Webster Inc.) with contact force capability, aiming for an even distribution of at least 150 points across all atrial regions, up to and including the PV ostia but excluding points within the PV. Only points with contact force >10 g were included for analysis. Mapping was performed in an identical fashion in the right atrium (RA) after LA ablation but before any RA ablation (e.g., cavotricuspid isthmus ablation).
Electrogram analysis was performed off-line after the procedure. Points were analyzed at 200 mm/s sweep speed for fractionation, voltage, and scar. Complex fractionated electrograms (CFEs) were defined as electrograms with ≥3 deflections and duration ≥50 ms. Unipolar and bipolar voltages were recorded for each point as the maximum voltage difference between the highest and lowest amplitude deflections. Points with bipolar voltage <1.5 mV were defined as reduced voltage, <0.5 mV as low voltage, and <0.05 mV as scar. For the purposes of regional analysis, the atria were divided into 4 segments for the RA and 5 segments for the LA (Figure 1). The PV antrum was defined as the LA region within a circumferential ring 2 cm proximal to the PV ostia, approximating a typical wide encirclement ablation line (marked in green in Figure 1). Percentages represent the proportion of total points across the entire atria (for global analysis) or within each region (for regional analysis) meeting the defined criteria for CFE, low voltage, or scar. Global and regional voltages were determined by the average voltage across the entire atria for global analysis or within each region for regional analysis.
Conduction velocity (CV) in each region was determined using a methodology previously described (9). In brief, pairs of points were selected in each region perpendicular to isochrones measured at 5 isochronal steps in areas of least isochronal crowding. CV was determined by dividing the measured shortest surface distance between point pairs by the difference in local activation time. Regional CV was determined as the average CV measured from 5 different point pairs in each region. Global CV consisted of the average of each regional CV within each atrium.
Pulmonary vein cycle length
Pulmonary vein cycle length (PVCL) was measured using the methodology described by Pascale et al. (10). In brief, before ablation, the multipolar catheter was placed in each PV for 60 s. Average PVCL for each vein was determined as the average of 100 consecutive PV cycle lengths. Average PVCL for each patient was the average of each measured PV. Average LAA CL was used as a surrogate for LA AF cycle length and was measured in an identical manner.
Data are expressed as mean ± SD unless otherwise indicated. After assessment of normal distribution with the Kolmogorov-Smirnov test, 2-group comparisons were made using the Student’s t-test for continuous variables or the chi-square test for categorical variables. The independent-samples Mann-Whitney U test was used for non-normally distributed variables. Correlation was performed using a Pearson correlation test. A 2-tailed p < 0.05 was considered significant. Analyses were conducted using SPSS software, version 24 (IBM, Chicago, Illinois).
Forty patients with persistent AF underwent biatrial mapping (20 in the HF group and 20 in the NLV group). Baseline characteristics are listed in Table 1. The HF group had an average LVEF of 33 ± 8.4% compared to 61 ± 3.6% in the NLV group (p < 0.001). Both groups were well matched with respect to age, gender, body mass index, comorbidities, biatrial dimensions, and AF burden, although expectedly the HF group had higher average CHADS2 (1.38 ± 0.86 vs. 0.79 ± 0.71; p = 0.011) and CHA2DS2-VASc scores (2.19 ± 1.21 vs. 1.00 ± 0.82; p = 0.001) compared to the NLV group.
There were expected differences in medications with anti-HF therapy, with beta-blocker use (100% vs. 45%; p < 0.001), spironolactone use (45% vs. 0%; p < 0.001), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy (95% vs. 65%; p = 0.018), and diuretic therapy (50% vs. 0%; p < 0.001) being significantly more frequent in the HF group. The use of any antiarrhythmic drug was equivalent between groups (55% vs. 65%; p = 0.52). Fifty percent of patients (9 of 18) in the HF group had CMR-detected late gadolinium enhancement. In the NLV group, the average E/e′ was 7.5 ± 1.3, with no patients having E/e′ ≥9.2, suggesting significant HF with preserved ejection fraction was unlikely (11,12).
There was no difference between groups with regard to the number of mapping points in both the LA and RA (HF vs. NLV: LA: 221 ± 79 vs. 210 ± 59; p = 0.62; RA: 200 ± 36 vs. 224 ± 59; p = 0.14) (Table 2, Figure 2).
In the LA, global unipolar and bipolar voltages were significantly lower in the HF group (unipolar: 2.36 ± 0.92 mV; bipolar: 1.47 ± 0.60 mV) compared to the NLV group (unipolar: 3.58 ± 1.07 mV; p < 0.001; bipolar: 2.28 ± 0.69 mV; p < 0.001). Voltage heterogeneity, as measured by covariance (SD/mean), was significantly increased in the HF compared to the NLV group (unipolar: 0.60 ± 0.12 vs. 0.47 ± 0.07; p < 0.001; bipolar: 0.75 ± 0.15 vs. 0.61 ± 0.07; p < 0.001).
In the RA, global unipolar and bipolar voltages were significantly lower in the HF group (unipolar: 1.88 ± 0.44 mV; bipolar: 1.45 ± 0.36 mV) compared to the NLV group (unipolar: 2.67 ± 0.84 mV; p = 0.001; bipolar: 2.13 ± 0.75 mV; p = 0.001). Voltage heterogeneity, as measured by covariance (SD/mean), was also increased in the HF compared to the NLV group (bipolar: 0.80 ± 0.11 vs. 0.70 ± 0.11; p = 0.006).
HF in both atria was associated with a significant increase in reduced-voltage (≤1.5 mV) points (LA: 59.9 ± 19.9% vs. 35.6 ± 20.2%; p < 0.001; RA: 64.2 ± 12.9% vs. 44.8 ± 20.0%; p = 0.001) and low-voltage (≤0.5 mV) points (LA: 23 ± 17% in HF vs. 6.3 ± 5.9% in NLV; p < 0.001; 20 ± 11% vs. 11 ± 7.9%; p = 0.006) compared to the NLV group.
Scar points (bipolar voltage ≤0.05) were found more frequently in the HF group in the LA (1.4 ± 1.5% vs. 0.2 ± 0.9%; p = 0.005) and RA (1.7 ± 3.9% vs. 0%; p = 0.09). However, in both atria, a significantly higher proportion of patients in the HF group had scar present (LA: 75% vs. 10%; p < 0.001; RA: 50% vs. 0%; p < 0.001).
Within the HF group, atrial tissue voltage was significantly higher in patients with tachycardia- or arrhythmia-mediated cardiomyopathy (TCMP), as defined by an improvement in LVEF to ≥50% after catheter ablation (n = 11), compared to those who did not demonstrate LV recovery (non-TCMP; n = 9). Bipolar voltage was 1.72 ± 0.64 in TCMP versus 1.20 ± 0.44 mV in non-TCMP (p = 0.045); unipolar voltage was 2.67 ± 0.95 in TCMP versus 1.92 ± 0.60 mV in non-TCMP (p = 0.048); and low voltage (<0.5 mV) was 17 ± 16% in non-TCMP versus 31 ± 14% in non-TCMP (p = 0.05).
In the HF group, global CV was significantly slower in the RA (0.91 ± 0.17 m/s vs. 1.03 ± 0.08 m/s; p = 0.026), with a nonsignificant difference in the LA (0.98 ± 0.21 m/s vs. 1.06 ± 0.15 m/s; p = 0.22) (Table 3).
Complex fractionated electrograms
The HF group was associated with a significant increase in CFEs in both atria compared to the NLV group (LA: 31 ± 17% vs. 9.1 ± 8.5%; p < 0.001; RA: 28 ± 14% vs. 11 ± 8.5%; p < 0.001).
Regional assessment of atrial substrate
Bipolar voltage was significantly reduced in the antrum in the HF group compared to the NLV group (1.18 ± 0.51 mV vs. 2.00 ± 0.68 mV; p < 0.001). In the HF group, antral bipolar voltage was significantly lower in the antral compared to the nonantral region (1.18 ± 0.51 mV vs. 1.76 ± 0.80 mV; p = 0.016). In the NLV group, no significant difference was seen between antral and nonantral voltage (2.01 ± 0.68 mV vs. 2.39 ± 0.75 mV; p = 0.10). CFEs were significantly increased in the antrum in the HF group compared to the NLV group (40 ± 15% vs. 15 ± 14%; p < 0.001). Again within the HF group, CFEs were most pronounced in the antrum versus the nonantral region (26 ± 13%; p = 0.022). Within the NLV group, no significant difference was seen between antral and nonantral regions (8.2 ± 7.1%; p = 0.10). HF was associated with a significant increase in low voltage (25 ± 25% vs. 9.5 ± 11% in the NLV group; p < 0.016) within the PV antrum (Tables 3 and 4).
Other regional LA analysis
Tissue voltage was reduced in the HF group in all subregions (Figure 1) of the LA (Table 3, Figures 2A and 2B). In the posterior LA, HF was associated with a significant reduction in voltage (bipolar: 1.34 ± 0.57 vs. 2.18 ± 0.77; p < 0.001; unipolar: 2.23 ± 0.89 vs. 3.59 ± 1.1 ± 9; p < 0.001) and regional low voltage (p < 0.001). Atrial scar was more frequent in proportion (2.4 ± 3.3% vs. 0.1 ± 0.4%; p = 0.005) and number of patients with scarring in HF (50% vs. 10% in NLV). In the posterior LA in the HF group, CFEs were significantly greater (32 ± 19% vs. 8.8 ± 8.3% in NLV; p < 0.001). Significantly reduced tissue voltage in the HF group was also pronounced in the septum.
In AF, the average PVCL was significantly longer in the HF group compared to the NLV group (185 ± 27 ms vs. 165 ± 19 ms; p = 0.016) (Figure 2B). The average PVCL of the fastest PV (PVFPVAverage) was also significantly slower in the HF group (172 ± 24 ms vs. 155 ± 17 ms; p = 0.013). The average of each parameter relative to the LAA cycle length was also significantly higher in the HF versus the NLV group (PV4PVAverage/LAA: 1.06 ± 0.09 vs. 0.99 ± 0.10; p = 0.028; PVFPVAverage/LAA: 1.03 ± 0.12 vs. 0.93 ± 0.10; p = 0.015); PVFast/LAA: 0.71 ± 0.11 vs. 0.57 ± 0.10; p < 0.001). Significantly more patients in the HF group had a ratio of PV4PVAverage/LAA or PVFPVAverage/LAA >1 (PV4PVAverage/LAA: 95% vs. 45%; p < 0.001; PVFPVAverage/LAA: 60% vs. 25%; p = 0.025). There was a significant correlation between PV4PVAverage and bipolar voltage (R = −0.62; p < 0.001) and complex fractionated activity (R = 0.46; p = 0.001) in the antrum (Figure 3).
AF and HF frequently coexist; however, whether HF confers a cumulative impact on atrial structural remodeling over and above the impact of AF itself has not been previously explored. In the present study, we undertook detailed biatrial substrate analysis in patients with persistent AF both with and without LV dysfunction. In persistent AF, patients with HF demonstrated a significant reduction in biatrial unipolar and bipolar tissue voltages; increase in biatrial voltage heterogeneity, low voltage, and scar; increase in biatrial complex fractionated activity; and slowing in PV electrical activity in AF that correlated with voltage and complex atrial activity at the PV antrum.
Atrial substrate in HF
Pathophysiological mechanisms responsible for AF and HF create a complex interplay and “chicken-and-egg” relationship between 2 common cardiac conditions. Sanders et al. (13) elegantly demonstrated structural remodeling in the RA in patients with HF in the absence of AF. HF was associated with reduced bipolar voltage, increased low voltage and scarring, and conduction slowing (13). The present study supports these earlier findings but extends mapping to the LA and PVs in the persistent AF population.
Previous studies looking at atrial structural remodeling as detected by atrial delayed gadolinium enhancement have shown mixed results. Oakes et al. (14) and McGann et al. (15) demonstrated no relationship between the extent of atrial delayed enhancement and systolic dysfunction. In contrast, Akkaya et al. (16) specifically compared the extent of LA delayed enhancement between patients with LVEF >50% and those with LVEF ≤50% and found significantly higher percentage of delayed enhancement in the reduced LVEF group. Furthermore, the extent of enhancement predicted the extent of LV recovery. However, no studies performed invasive assessment, and all included mixed etiologies of HF. Haldar et al. (17) demonstrated a significant increase in atrial fractionation in patients with persistent AF and HF of variable etiology. Although consistent with the findings in the present study, their retrospective analysis was performed during AF rather than in sinus rhythm; HF etiology included ischemic and valvular heart disease; and substrate analysis was confined to fractionation alone. In the present study in patients with equivalent durations of persistent AF, HF was associated with biatrial electrical and structural remodeling with reductions in tissue voltage, low voltage, and complex atrial activity. The adverse atrial remodeling demonstrated in the HF population in the present study may be representative of a primary global cardiomyopathy or may be driven by AF in patients vulnerable to systolic dysfunction.
CV was preserved in the LA despite being significantly reduced in the RA in the HF population. Differences in atrial architecture, such as the crista terminalis, may have enhanced conduction slowing in the RA and may explain the observed differences between atrial chambers.
PV antrum and regional analysis
In the present study, we demonstrated a significant reduction in voltage and increased fractionation in all regions of the LA in HF, most notably in the posterior and septal LA. In addition, tissue voltage was significantly lower in the PV antrum compared with surrounding nonantral sites with HF, a difference not observed in the NLV group. This study is the first to demonstrate that this remodeling in the PV antrum is associated with a slowing of PV electrical activity. This more extensive remodeling of the PV antrum reinforces the role of wide encirclement rather than ostial ablative strategy in this patient population. Cabrera et al. (18,19) demonstrated histological changes in the PV antral region, particularly the interpulmonary and PV/LAA ridge, predisposing to the spread of AF activity, and a recent clinical trial highlighted the clinical implications of remodeling this region (20). Recent meta-analyses have demonstrated that a wide antral approach to pulmonary vein isolation (PVI) may be more effective in achieving long-term freedom from AF in patients with persistent AF (21,22).
Roberts-Thomson et al. (23) demonstrated the importance of the posterior LA in AF in an open chest epicardial human study in patients with structural heart disease and LV dysfunction. CMR-detected atrial late gadolinium enhancement has similarly been shown to predominate in the posterior LA (14,15). These findings have important clinical implications and may in part explain a recent observation from a randomized study of catheter ablation versus amiodarone in AF and HF. A retrospective analysis demonstrated that catheter ablation was more successful if PVI included posterior LA isolation compared with PVI alone (79% vs. 26%; p < 0.001) in patients with HF (24). The presence of low-voltage regions within the PV antrum and posterior LA provides mechanistic support to the observation of improved outcomes when isolation of the posterior LA is included with PVI during catheter ablation for AF in HF.
PV AF cycle length was significantly slower in HF patients with persistent AF, a finding that to our knowledge has not been previously demonstrated. Pascale et al. (25) demonstrated that the shortest measured PVCL relative to LAA AF cycle length was predictive of recurrence after AF ablation. Walters et al. (26) demonstrated that the AF cycle length within the coronary sinus correlated with LA structural remodeling (bipolar voltage, CV, and complex electrograms) in patients with long-standing persistent AF. However, their study did not specifically correlate structural remodeling with PVCL and did not include patients with HF. Intriguingly, in the present study there was a significant relationship between PVCL and PV antral voltage. Lower tissue voltage was associated with slowing of PVCL in AF in HF, and one may speculate that reduced PV firing and more extensive atrial substrate may provide some insight into the reported lower success of PVI in patients with HF (8,27).
In the present study, patients with persistent AF and HF demonstrated biatrial electrical and structural changes that may in part explain the reduced success of pharmacotherapy and catheter ablation compared to patients without systolic impairment (27,28). This has important implications, as recent studies have suggested that catheter ablation in HF may have additional benefits of recovery of systolic dysfunction after restoration of sinus rhythm (4,6,29–31). Ling et al. (29) demonstrated that in patients with AF and systolic dysfunction without delayed ventricular enhancement on CMR, LV function normalized after successful catheter ablation. In the STAR AF II (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation II) trial, there was no significant difference in ablation outcomes for persistent AF with PVI versus PVI plus substrate modification; however, the proportion of patients with HF was just 4% (32). The presence of a slower PVCL and more extensive atrial substrate may require an alternate ablation strategy to improve outcomes in this population.
To date, no randomized trials have compared ablation strategies in patients with normal and reduced ejection fraction, although importantly, substrate modification strategies such as posterior wall isolation have yet to be prospectively evaluated in a randomized fashion. The AATAC-AF (Ablation Versus Amiodarone for Treatment of Persistent Atrial Fibrillation in Patients With Congestive Heart Failure and an Implanted Device) trial demonstrated the superiority of catheter ablation over amiodarone in patients with AF and HF (24). Retrospective analysis identified improved outcomes when posterior wall isolation was included beyond PVI alone (79% vs. 36%; p < 0.001) (24). This present study demonstrating extensive biatrial substrate in the AF/HF population offers a pathophysiological explanation to support ongoing research into substrate modification strategies in this specific patient population.
The aim of the present study was to determine the biatrial substrate in patients with persistent AF and HF not explained by ischemia or valvular dysfunction. A significant proportion of HF patients in this study had an underlying arrhythmia-mediated cardiomyopathy with normalization of LVEF after restoration of sinus rhythm with catheter ablation. These patients displayed less advanced atrial substrate compared to those in whom LV function failed to normalize after ablation. This may explain the improved freedom from AF with catheter ablation in patients with arrhythmia-mediated cardiomyopathy compared with known structural heart disease (31,33).
The exclusion of patients with structural heart disease such as ischemic or valvular heart disease may limit the extrapolation of the study findings to these cardiac conditions. In addition, patients with paroxysmal AF were not included. This mechanistic study was designed to characterize the biatrial substrate in patients with persistent AF and HF, rather than outcome with catheter ablation. Use of a 3.5-mm bipolar ablation catheter with a contact force >10 g may have resulted in both undersensing of local electrograms and oversensing of far-field electrograms at the LA septum. The cutoff value of <0.5 mV for low voltage, although consistent with other substrate analysis studies, has not yet been histologically validated as a marker of structural remodeling in humans.
HF is associated with significant reductions in biatrial tissue voltage, fractionation, and prolongation of AF cycle length within the PVs. More advanced biatrial remodeling may have implications for ablation strategies and explain the relative ineffectiveness of antiarrhythmic therapy in patients with AF and HF.
COMPETENCY IN MEDICAL KNOWLEDGE: Both AF and HF exert adverse remodeling influences on the atria; however, the contribution of systolic dysfunction, over and above that of AF itself, is unknown. Concurrent systolic impairment and persistent AF is associated with a significantly more advanced atrial substrate than in persistent AF without systolic impairment. This may explain the poorer outcomes seen with rhythm control strategies in patients with systolic HF and AF.
TRANSLATIONAL OUTLOOK: Patients with concurrent AF and systolic dysfunction may require more extensive treatment approaches, including aggressive risk-factor modification, additional substrate modification, and other anti-HF treatments to optimize rhythm control success. The reversibility of this additional remodeling after improvement in systolic function remains to be determined.
This research has been supported in part by the Victorian Government’s Operational Infrastructure Funding. Drs. Prabhu, Ling, McLellan, Voskoboinik, Nalliah, and Pathik have received funding from the Australian National Health and Medical Research Council (NHMRC) and/or the National Heart Foundation of Australia. Drs. Prabhu and McLellan have also received funding from the Baker Heart and Diabetes Research Institute (Melbourne, Australia). Drs. Kalman, Lee, and Kistler have been supported in part by the NHMRC. Dr. Kalman has served on the advisory board of Biosense Webster; and has received research and fellowship support from Medtronic, Abbott, and Biosense Webster. All other authors have reported that they have no relationships relevant to this paper to disclose. Katia Zeppenfeld, MD, served as Guest Editor for this article.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Abbreviations and Acronyms
- atrial fibrillation
- complex fractionated electrogram
- cardiac magnetic resonance
- conduction velocity
- heart failure
- left atrium
- left atrial appendage
- left ventricle
- left ventricular ejection fraction
- normal left ventricle
- pulmonary vein
- pulmonary vein cycle length
- average pulmonary vein cycle length of the fastest pulmonary vein
- pulmonary vein isolation
- right atrium
- tachycardia- or arrhythmia-mediated cardiomyopathy
- Received March 22, 2017.
- Revision received August 24, 2017.
- Accepted August 28, 2017.
- 2018 American College of Cardiology Foundation
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