Determining the Optimal Dose of Adenosine for Unmasking Dormant Pulmonary Vein Conduction Following Atrial Fibrillation Ablation: Electrophysiological and Hemodynamic Assessment. DORMANT-AF Study.

INTRODUCTION: ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. DORMANT-AF STUDY: The significance of adenosine induced dormant pulmonary vein (PV) conduction in atrial fibrillation (AF) ablation remains controversial. The optimal dose of adenosine to determine dormant PV conduction is yet to be systematically explored. METHODS AND RESULTS: ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. DORMANT-AF STUDY: Consecutive patients undergoing index AF ablation received 3 adenosine doses (12, 18, and 24 mg) in a randomized blinded order, immediately after pulmonary vein isolation (PVI). Electrophysiological (PR prolongation, AV block (AVB) and PV reconnection) and hemodynamic (BP) parameters were measured. A total, 339 doses (113/dose) assessed 191 PVs in 50 patients (66% male, 72% PAF, 52% hypertensive). Dormant PV conduction occurred in 28% of patients (16.5% [32] of PVs). All cases were associated with AVB (AVB: PV reconnection vs. no PV reconnection 100% vs. 83%, P = 0.007). AVB occurred more frequently at 24 mg versus 12 mg (92% vs. 82%, P = 0.019) but not versus 18 mg (91%, P = 0.62). AVB duration progressed between 12 mg (12.0 ± 8.9 seconds), 18 mg (16.1 ± 9.1 seconds, P = 0.001), and 24 mg (19.0 ± 9.3 seconds, P < 0.001) doses. MBP fell further at 24 mg (ΔMBP: 27 ± 12 mmHg) and 18 mg (26 ± 13 mmHg) doses compared to 12 mg (22 ± 10 mmHg vs., P < 0.001). A significant reduction in AVB in patients >110 kg (65% vs. 91% in 70-110 kg group, P < 0.001) in response to adenosine was seen. CONCLUSION: ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. DORMANT-AF STUDY: An adenosine dose producing AVB is required to unmask dormant PV conduction. AVB is significantly reduced in patients >110 kg. Weight and dosing variability may in part explain the conflicting results of studies evaluating the clinical utility of adenosine in PVI.

A comparison of the electrophysiologic and electroanatomic characteristics between the right and left atrium in persistent atrial fibrillation: Is the right atrium a window into the left?

INTRODUCTION: The right atrium (RA) is readily accessible; however, it is unclear whether changes in the RA are representative of the LA. We performed detailed biatrial electroanatomic mapping to determine the electrophysiological relationship between the atria. METHODS AND RESULTS: Consecutive patients with persistent AF underwent biatrial electroanatomical mapping with a contact force catheter acquiring points with a CF >10 g prior to ablation. Points were analyzed for tissue voltage, complex electrograms, low voltage (<0.5 mV), scar (<0.05 mV), and conduction velocity (CV). Forty patients (mean age 59 ± 9.2 years, AF duration 12.9 ± 9.2 months, LA area: 28 ± 5.2, RA area: 25 ± 6.4 mm2 , LVEF: 44 ± 15%) underwent mapping during CS pacing. Bipolar voltage (R = 0.57, P <0.001), unipolar voltage (R = 0.68, P <0.001), low voltage (<0.5 nV) (R = 0.48, P = 0.002), fractionation (R = 0.73, P <0.001), and CV (R = 0.49, P = 0.001) correlated well between atria. There was no difference in global bipolar voltage (LA 1.89 ± 0.77 vs. RA 1.77 ± 0.57 mV, P = 0.57); complex electrograms (LA 20% vs. RA 20%, P = 0.99) or low voltage (LA 15% vs. RA 16%, P = 0.84). Global unipolar voltage was significantly higher in the LA compared to the RA (2.95 ± 1.14 vs. 2.28 ± 0.65 mV, P = 0.002) and CV was significantly slower in the RA compared to the LA (0.93 ± 0.15 m/s vs. 1.01 ± 0.19 m/s, P = 0.001). CONCLUSION: AF is associated with remodeling processes affecting both atria. The more accessible RA provides an insight into the biatrial process associated with AF in various disease states without trans-septal access.

Isolation of the posterior left atrium for patients with persistent atrial fibrillation: routine adenosine challenge for dormant posterior left atrial conduction improves long-term outcome.

AIMS: Catheter ablation to achieve posterior left atrial wall (PW) isolation may be performed as an adjunct to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF). We aimed to determine whether routine adenosine challenge for dormant posterior wall conduction improved long-term outcome. METHODS AND RESULTS: A total of 161 patients with persistent AF (mean age 59 ± 9 years, AF duration 6 ± 5 years) underwent catheter ablation involving circumferential PVI followed by PW isolation. Posterior left atrial wall isolation was performed with a roof and inferior wall line with the endpoint of bidirectional block. In 54 patients, adenosine 15 mg was sequentially administered to assess reconnection of the pulmonary veins and PW. Sites of transient reconnection were ablated and adenosine was repeated until no further reconnection was present. Holter monitoring was performed at 6 and 12 months to assess for arrhythmia recurrence. Posterior left atrial wall isolation was successfully achieved in 91% of 161 patients (procedure duration 191 ± 49 min, mean RF time 40 ± 19 min). Adenosine-induced reconnection of the PW was demonstrated in 17%. The single procedure freedom from recurrent atrial arrhythmia was superior in the adenosine challenge group (65%) vs. no adenosine challenge (40%, P < 0.01) at a mean follow-up of 19 ± 8 months. After multiple procedures, there was significantly improved freedom from AF between patients with vs. without adenosine PW challenge (85 vs. 65%, P = 0.01). CONCLUSION: Posterior left atrial wall isolation in addition to PVI is a readily achievable ablation strategy in patients with persistent AF. Routine adenosine challenge for dormant posterior wall conduction was associated with an improvement in the success of catheter ablation for persistent AF.

Diffuse Ventricular Fibrosis on Cardiac Magnetic Resonance Imaging Associates With Ventricular Tachycardia in Patients With Hypertrophic Cardiomyopathy.

INTRODUCTION: Non-sustained ventricular tachycardia (NSVT) is a risk factor for sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We aimed to assess whether diffuse ventricular fibrosis on cardiac magnetic resonance (CMR) imaging could be a surrogate marker for ventricular arrhythmias in patients with HCM. METHODS: A total of 100 patients with HCM (mean age 51 ± 13 years, septal wall thickness 20 ± 5 mm) underwent CMR with a 1.5 T scanner to determine the presence of ventricular late gadolinium enhancement (LGE) for focal fibrosis, and post-contrast T1 mapping for diffuse ventricular fibrosis. The presence of NSVT was determined by Holter monitoring and a subset of high risk patients received an implantable cardioverter-defibrillator (ICD). RESULTS: NSVT was detected in 23 of 100 patients with HCM. Focal ventricular fibrosis (by LGE) was observed in 87%, with no significant difference between patients with (96%) or without NSVT (86%, P = 0.19). However, LGE mass was greater in patients with (16.5 ± 19.1 g) versus without NSVT (7.6 ± 10.2 g, P < 0.01). NSVT was associated with a significant reduction in ventricular T1 relaxation time (422 ± 54 milliseconds) versus patients without NSVT (512 ± 115 milliseconds; P < 0.001). There was significant reduction in ventricular T1 relaxation time in patients with (430 ± 48 milliseconds) versus without aborted SCD (495 ± 113 milliseconds; P = 0.01) over a mean follow-up of 40 ± 10 months. On multivariate analysis post-contrast ventricular T1 relaxation time and septal wall thickness were the only predictors of NSVT. CONCLUSION: Post-contrast T1 relaxation time on CMR is associated with ventricular arrhythmias in patients with HCM. Diffuse ventricular fibrosis may be an important marker of arrhythmic risk in patients with HCM.

The Impact of Known Heart Disease on Long-Term Outcomes of Catheter Ablation in Patients with Atrial Fibrillation and Left Ventricular Systolic Dysfunction: A Multicenter International Study.

BACKGROUND: Catheter ablation for AF is an effective treatment for patients with AF and systolic LV dysfunction; however, the clinical outcome is variable. We evaluated the impact of cardiomyopathy etiology on long-term outcomes post-catheter ablation. METHODS: Patients undergoing AF ablation across 3 centers (2 Australian, 1 UK) from 2002 to 2014, with LVEF<45% were evaluated. Patients were stratified into those with known heart disease as a cause of cardiomyopathy (KHD), and those with idiopathic dilated cardiomyopathy (IDCM). RESULTS: One hundred and one patients (IDCM = 77, KHD = 24) with AF and LVEF <45% underwent AF ablation. The KHD group (ischemic HD in 67%) were older (61 ± 7 vs. 55 ± 11 years, P = 0.005), with a higher CHADS2 score (2.0 ± 0.8 vs. 1.6 ± 0.7, P = 0.016), but otherwise well matched. After mean follow-up of 36 ± 23 months, AF control was greater in the IDCM group (82% vs. 50% in KHD, P < 0.001). On multivariate analysis IDCM was associated with long-term AF control (P = 0.033). The IDCM group had less functional impairment at follow-up (NYHA class 1.5 ± 0.7 vs. 2.0 ± 0.8, P = 0.005) and improved LVEF (50 ± 11% vs. 38 ± 10%, P < 0.001). Super responders (EF improvement >15%) were overwhelmingly in the IDCM group (94% vs. 6%, P < 0.001) with greater AF control (89% vs. 61%, P < 0.001). All-cause mortality was significantly higher in the KHD group (17% vs. 1.3%, P = 0.002). CONCLUSION: IDCM was associated with greater AF control, and improvement in symptoms and LVEF compared to patients with KHD post-AF ablation. AF is an important reversible cause of HF in patients with an unexplained CM and catheter ablation an effective treatment option.

A minimal or maximal ablation strategy to achieve pulmonary vein isolation for paroxysmal atrial fibrillation: a prospective multi-centre randomized controlled trial (the Minimax study).

AIMS: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation of atrial fibrillation (AF). The intervenous ridge (IVR) may be incorporated into ablation strategies to achieve PVI; however, randomized trials are lacking. We performed a randomized multi-centre international study to compare the outcomes of (i) circumferential antral PVI (CPVI) alone (minimal) vs. (ii) CPVI with IVR ablation to achieve individual PVI (maximal). METHODS AND RESULTS: Two hundred and thirty-four patients with paroxysmal AF underwent CPVI and were randomized to a minimal or maximal ablation strategy. The primary outcome of recurrent atrial arrhythmia was assessed with 7-day Holter monitoring at 6 and 12 months. PVI was achieved in all patients. Radiofrequency ablation time was longer in the maximal group (46.6 ± 14.6 vs. 41.5 ± 13.1 min; P < 0.01), with no significant differences in procedural or fluoroscopy times. At mean follow-up of 17 ± 8 months, there was no difference in freedom from AF after a single procedure between a minimal (70%) and maximal ablation strategy (62%; P = 0.25). In the minimal group, ablation was required on the IVR to achieve electrical isolation in 44%, and was associated with a significant reduction in freedom from AF (57%) compared with the minimal group without IVR ablation (80%; P < 0.01). CONCLUSION: There was no statistically significant difference in freedom from AF between a minimal and maximal ablation strategy. Despite attempts to achieve PVI with antral ablation, IVR ablation is commonly required. Patients in whom antral isolation can be achieved without IVR ablation have higher long-term freedom from AF (the Minimax study; ACTRN12610000863033).

Deglutition-Induced Atrial Tachycardia Localised with Contact Force-Guided Activation Mapping.

Deglutition-induced atrial tachycardia is a rare arrhythmia with a poor response to medical therapy. Electrophysiological study is challenging due to the dependence of induction on swallowing. We present a novel approach to management of deglutition-induced atrial tachycardia arising from right superior pulmonary vein. Use of minimal conscious sedation and repeated swallow challenge inductions, together with contact force-guided mapping were key determinants of success. We review published cases, discussing potential mechanisms including oesophageal distension and neural reflexes.

The transesophageal echo probe may contribute to esophageal injury after catheter ablation for paroxysmal atrial fibrillation under general anesthesia: a preliminary observation.

INTRODUCTION: The transesophageal echo probe (TEE) is commonly used before and during atrial fibrillation (AF) ablation under general anesthesia (GA). We sought to determine the potential contribution of the TEE probe to esophageal injury after pulmonary vein isolation (PVI) alone for paroxysmal AF. METHODS AND RESULTS: Seventy-six patients undergoing PVI with TEE, PVI/TEE, 16 undergoing PVI without TEE (PVI/No TEE), and 27 undergoing TEE without any left atrial ablation (TEE/No LA ablation) under GA were included. Posterior wall ablation was power (20-25 W) and time limited (electrogram attenuation or ≤30 s). Esophageal capsule endoscopy (n = 206) was performed pre- and post-procedure and at 2 weeks. Esophageal lesions were seen in 30% of PVI/TEE, 0% of patients in the PVI/No TEE (P = 0.009), and 22% of TEE/No LA ablation groups (P = 0.47 vs. PVI/TEE). There were no instances of esophageal bleeding, perforation, or need for gastrointestinal intervention. Self-resolving dysphagia was the only reported symptom (5%). All lesions healed within 2 weeks. There was no significant difference in the location or morphological appearance of esophageal lesions seen in the PVI/TEE versus TEE/No LA ablation groups. CONCLUSIONS: Esophageal lesions were seen in 30% of patients undergoing PVI alone under GA with use of TEE and in a similar proportion (22%) of patients undergoing TEE in the absence of left atrial ablation. This study makes the preliminary observation that one must be cognizant of the TEE probe as a potential contributor to esophageal injury after AF ablation. Larger studies are needed to confirm these findings.

The role of adenosine following pulmonary vein isolation in patients undergoing catheter ablation for atrial fibrillation: a systematic review.

INTRODUCTION: Pulmonary vein reconnection is a major limitation of pulmonary vein isolation (PVI) for symptomatic atrial fibrillation (AF). Adenosine may unmask dormant PV conduction and facilitate consolidation of PV isolation. We performed a systematic review of the literature to determine the impact of routine adenosine administration on clinical outcomes in patients undergoing PVI. METHODS: References and electronic databases reporting AF ablation and adenosine following PVI were searched through to 31 July 2012. Six studies included 544 patients to assess the impact of catheter ablation to target adenosine-induced PV reconnection on AF ablation outcome and 3 studies included 612 patients to assess the impact of adenosine testing on AF ablation outcome. Relative risks were calculated and combined in a meta-analysis using random effects modeling. RESULTS: Routine adenosine testing for PV reconnection with additional targeted ablation resulted in a significant increase in freedom from AF post-PVI (RR 1.25; 95% CI 1.12-1.40; P < 0.001). However, within the group of patients undergoing adenosine testing, those with reconnection identified a population with a trend to reduction in freedom from AF despite the use of further targeted ablation in the reconnection group (RR 0.91 with 95% CI 0.81-1.03; P = 0.15). CONCLUSION: Routine adenosine testing is associated with an improvement in freedom from AF post-PVI. Paradoxically acute adenosine-induced PV reconnection may portend a greater likelihood of AF recurrence despite additional ablation. Randomized controlled trials are required to determine the role of adenosine testing post-PVI.

Cardiac magnetic resonance imaging predicts recovery of left ventricular function in acute onset cardiomyopathy.

BACKGROUND: In acute onset cardiomyopathy, acute myocarditis is an important cause, as it is associated with a greater likelihood of recovery of cardiac function and its presence may direct specific therapies. Myocarditis can be detected by cardiac magnetic resonance imaging (CMR); however its diagnostic utility and relation to prognosis in acute onset cardiomyopathy are unknown. METHODS: We performed CMR on 61 patients with acute onset cardiomyopathy and a left ventricular ejection fraction (LVEF) <55%. CMR included assessment of myocardial function, relative myocardial oedema, myocardial inflammation (using global relative enhancement [GRE] of the myocardium 4 minutes post Gad-DTPA contrast) and necrosis or fibrosis (with late gadolinium enhancement [LGE]). Patients were followed up at six months to evaluate LVEF, morbidity and mortality. RESULTS: There was a greater improvement in LVEF at follow up in those with myocardial inflammation identified by elevated GRE compared to those without (mean increase 19.2±2.5% vs. 6.7±1.7%, p<0.001). However, the presence of myocardial oedema or LGE alone was not associated with a greater recovery of LVEF (p=NS for both). Myocardial inflammation in patients with a baseline LVEF<35% was also associated with a greater recovery of LVEF (mean increase 21.5±2.9% vs. 9.1±3.0%, p<0.01). CONCLUSION: Myocardial inflammation identified by an elevated GRE predicts recovery of LV function in patients with acute onset cardiomyopathy.

Medical Management of Rheumatic Heart Disease: A Systematic Review of the Evidence.

Rheumatic heart disease (RHD) is an important cause of heart disease globally. Its management can encompass medical and procedural (catheter and surgical) interventions. Literature pertaining to the medical management of RHD from PubMed 1990-2016 and via selected article reference lists was reviewed. Areas included symptom management, left ventricular dysfunction, rate control in mitral stenosis, atrial fibrillation, anticoagulation, infective endocarditis prophylaxis, and management in pregnancy. Diuretics, angiotensin blockade and beta-blockers for left ventricular dysfunction, and beta-blockers and If inhibitors for rate control in mitral stenosis reduced symptoms and improved left ventricular function, but did not alter disease progression. Rhythm control for atrial fibrillation was preferred, and where this was not possible, rate control with beta-blockers was recommended. Anticoagulation was indicated where there was a history of cardioembolism, atrial fibrillation, spontaneous left atrial contrast, and mechanical prosthetic valves. While warfarin remained the agent of choice for mechanical valve implantation, non-vitamin K antagonist oral anticoagulants may have a role in RHD-related AF, particularly with valvular regurgitation. Evidence for anticoagulation after bioprosthetic valve implantation or mitral valve repair was limited. RHD patients are at increased risk of endocarditis, but the evidence supporting antibiotic prophylaxis before procedures that may induce bacteremia is limited and recommendations vary. The management of RHD in pregnancy presents particular challenges, especially regarding decompensation of previously stable disease, the choice of anticoagulation, and the safety of medications in both pregnancy and breast feeding.

Biatrial Electrical and Structural Atrial Changes in Heart Failure: Electroanatomic Mapping in Persistent Atrial Fibrillation in Humans.

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.

Pulmonary vein activity does not predict the outcome of catheter ablation for persistent atrial fibrillation: A long-term multicenter prospective study.

BACKGROUND: Pulmonary vein (PV) isolation (PVI) remains the cornerstone of catheter ablation (CA) in persistent atrial fibrillation (AF) (PeAF), although less successful than for paroxysmal AF. Whether rapid or fibrillatory (PV AF) PV firing may identify patients with PeAF more likely to benefit from a PV-based ablation approach is unclear. OBJECTIVE: The purpose of this study was to determine the relationship between the PV cycle length (PVCL) and the PV AF outcome after CA. METHODS: Before ablation, the multipolar catheter was placed in each PV and the left atrial appendage (LAA) for 100 consecutive cycles. The presence of PV AF, the average PVCL of all 4 veins (PV4VAverage), the fastest vein average (PVFVAverage), the fastest cycle length (PVFast) both individually and relative to the average LAA cycle length were calculated. The ablation strategy included PVI and posterior wall isolation with a minimum of 12 months follow-up. RESULTS: A total of 123 patients underwent CA (age 62 ± 9.1 years; CHA2DS2-VASC score 1.6 ± 1.1; left ventricular ejection fraction 48% ± 13%; left atrial area 31 ± 8.7 cm2; AF duration 16 ± 17 months). PVI was achieved in 100% of patients. Multiprocedure success (MPS; freedom from AF/atrial tachycardia episodes lasting >30 seconds) was achieved in 76% of patients at 24 ± 8.1 months of follow-up after 1.2 ± 0.4 procedures. PV activity was not associated with MPS either absolutely (PV4VAverage [MPS no vs yes: 178 ± 27 ms vs 177 ± 24 ms; P = .92], PVFVAverage [P = .69], or PVFast [P = .82]) or as a ratio relative to the LAA cycle length (PV4VAverage/LAA 1.05 ± 0.11 vs 1.06 ± 0.21; P = .87). The presence of PV AF (31% vs 47%; P = .13) did not predict MPS. CONCLUSION: The rapidity of PV firing or presence of fibrillation within the PV was not predictive of outcome of CA for PeAF. PV activity does not identify patients most likely to benefit from a PV-based ablation strategy.

Regression of Diffuse Ventricular Fibrosis Following Restoration of Sinus Rhythm With Catheter Ablation in Patients With Atrial Fibrillation and Systolic Dysfunction: A Substudy of the CAMERA MRI Trial.

OBJECTIVES: This study sought to determine if diffuse ventricular fibrosis improves in patients with atrial fibrillation (AF)-mediated cardiomyopathy following the restoration of sinus rhythm. BACKGROUND: AF coexists in 30% of heart failure (HF) patients and may be an underrecognized reversible cause of left ventricular systolic dysfunction. Myocardial fibrosis is the hallmark of adverse cardiac remodeling in HF, yet its reversibility is unclear. METHODS: Patients with persistent AF and an idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%) were randomized to catheter ablation (CA) or ongoing medical rate control as a pre-specified substudy of the CAMERA-MRI (Catheter Ablation versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction-an MRI-Guided Multi-centre Randomised Controlled Trial) trial. All patients had cardiac magnetic resonance imaging scans (including myocardial T1 time), serum B-type natriuretic peptide, 6-min walk tests, and Short Form-36 questionnaires performed at baseline and 6 months. Sixteen patients with no history of AF or left ventricular systolic dysfunction were enrolled as normal controls for T1 time. RESULTS: Thirty-six patients (18 in each treatment arm) were included in this substudy. Demographics, comorbidities, and myocardial T1 times were well matched at baseline. At 6 months, patients in the CA group had a significant reduction in myocardial T1 time from baseline compared with the medical rate control group (-124 ms; 95% confidence interval [CI]: -23 to -225 ms; p = 0.0176), although it remained higher than that of normal controls at 6 months (p = 0.0017). Improvements in myocardial T1 time with CA were associated with significant improvements in absolute LVEF (+12.5%; 95% CI: 5.9% to 19.0%; p = 0.0004), left ventricular end-systolic volume (p = 0.0019), and serum B-type natriuretic peptide (-216 ng/l; 95% CI: -23 to -225 ng/l; p = 0.0125). CONCLUSIONS: The improvement in LVEF and reverse ventricular remodeling following successful CA of AF-mediated cardiomyopathy is accompanied by a regression of diffuse fibrosis. This suggests timely treatment of arrhythmia-mediated cardiomyopathy may minimize irreversible ventricular remodeling.

Panoramic characterization of endocardial left atrial activation during human persistent AF: Insights from non-contact mapping.

BACKGROUND: The relative importance of focal drivers, multiple wavelets, rotors and endocardial-epicardial circuits in the maintenance of persistent AF remains unclear. Our objective was to characterize AF wavefront (WF) dynamics during persistent AF. METHODS: The Ensite 3000 (St Jude Medical) non-contact mapping system was used to map the LA of 15 patients with persistent AF. Wavefronts were classified into planar WFs, rotors or focal WFs. For each new WF the site of origin, the unipolar electrogram, and propagation patterns were determined. RESULTS: AF was characterized by highly unstable patterns of activation with random combinations of 1-2 propagating planar wavefronts alternating with focal activations in a dynamic process. Stable reentry circuits and rotors were never seen. A total of 499 wavefront patterns were analyzed in this study (416 planar wavefronts and 83 focal wavefronts). In an individual patient planar WFs accounted for 67±35% of activations with lifespans of 98±86ms. Focal activations accounted for 29.7±33.5% of activations with lifespans of 76±95ms. The most common sites for new WF generation were the PVs (33%), LA roof (23%), anterior LA (15%), LAA (11%), and posterior LA (8%). The most common unipolar electrogram morphologies observed were QS pattern (34%), rS (29%), CFAE (26%), QR (7%) and Rs (4%), suggesting that WFs may originate from both the endocardial and epicardial surfaces. CONCLUSION: Human persistent AF is characterized by the formation of highly unstable WFs consisting of various combinations of one to two planar WFs and brief focal activations without any evidence of rotors or sustained focal sources.

The role of adenosine challenge in catheter ablation for atrial fibrillation: A systematic review and meta-analysis.

AIMS: Adenosine may unmask dormant PV conduction and facilitate consolidation of PV isolation. We performed a meta-analysis to determine the impact of adenosine administration on clinical outcomes in patients undergoing PVI. METHODS: References and electronic databases reporting AF ablation and adenosine following PVI were searched through to 22nd November 2015. The impact of adenosine on freedom from AF was assessed in twenty publications after radiofrequency ablation (RFA), and in four publications after cryoablation to achieve PVI. Relative risks were calculated and combined in a meta-analysis using random effects modeling. RESULTS: In patients undergoing RFA with adenosine challenge, there was a significant reduction in freedom from AF in patients with versus without adenosine induced reconnection (RR 0.86; 95%CI 0.77-0.98; p=0.02) particularly if no further ablation was performed (RR 0.66; 95%CI 0.50-0.87; p<0.01). There was no difference when comparing outcomes in studies of routine adenosine challenge vs no adenosine (RR 1.07; 95%CI 0.93-1.22; p=0.36). There was a non-significant trend to an increase in freedom from AF in patients receiving routine adenosine challenge (RR 1.18 95%CI 0.99-1.42; p=0.07) in non-randomized studies using cryoablation. CONCLUSION: Adenosine induced PV reconnection following PVI is associated with a significant increase in AF recurrence, particularly if the reconnection sites are not targeted for ablation. The routine use of adenosine may be beneficial in AF ablation if given early post-PVI, at sufficient dose and reconnection is ablated.

Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study.

BACKGROUND: Atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) frequently co-exist despite adequate rate control. Existing randomized studies of AF and LVSD of varying etiologies have reported modest benefits with a rhythm control strategy. OBJECTIVES: The goal of this study was to determine whether catheter ablation (CA) for AF could improve LVSD compared with medical rate control (MRC) where the etiology of the LVSD was unexplained, apart from the presence of AF. METHODS: This multicenter, randomized clinical trial enrolled patients with persistent AF and idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%). After optimization of rate control, patients underwent cardiac magnetic resonance (CMR) to assess LVEF and late gadolinium enhancement, indicative of ventricular fibrosis, before randomization to either CA or ongoing MRC. CA included pulmonary vein isolation and posterior wall isolation. AF burden post-CA was assessed by using an implanted loop recorder, and adequacy of MRC was assessed by using serial Holter monitoring. The primary endpoint was change in LVEF on repeat CMR at 6 months. RESULTS: A total of 301 patients were screened; 68 patients were enrolled between November 2013 and October 2016 and randomized with 33 in each arm (accounting for 2 dropouts). The average AF burden post-CA was 1.6 ± 5.0% at 6 months. In the intention-to-treat analysis, absolute LVEF improved by 18 ± 13% in the CA group compared with 4.4 ± 13% in the MRC group (p < 0.0001) and normalized (LVEF ≥50%) in 58% versus 9% (p = 0.0002). In those undergoing CA, the absence of late gadolinium enhancement predicted greater improvements in absolute LVEF (10.7%; p = 0.0069) and normalization at 6 months (73% vs. 29%; p = 0.0093). CONCLUSIONS: AF is an underappreciated reversible cause of LVSD in this population despite adequate rate control. The restoration of sinus rhythm with CA results in significant improvements in ventricular function, particularly in the absence of ventricular fibrosis on CMR. This outcome challenges the current treatment paradigm that rate control is the appropriate strategy in patients with AF and LVSD. (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction [CAMERA-MRI]; ACTRN12613000880741).

Atrial structure and function and its implications for current and emerging treatments for atrial fibrillation.

Left atrial (LA) structure and function are intimately related to the clinical phenotypes of atrial fibrillation (AF), and have direct implications for the success or otherwise of various therapeutic strategies. In conjunction with intrinsic structural characteristics of the LA, pathological remodelling to a large extent dictates the clinical course of AF. Remodelling is a product of the physiological and structural plasticity of the LA in disease states (including AF itself), and manifests as electrical, physical and structural changes that promote the substrate necessary for AF maintenance. The degree of remodelling impacts upon the efficacy of pharmacological, non-pharmacological and interventional treatments for AF. Evolving therapies seek to specifically target these processes although presently, several remain in the development phase. Catheter ablation (CA) is now firmly established as a highly effective treatment for AF, although increasing its efficacy in the remodelled LA of more severe AF phenotypes remains an ongoing challenge.

Reverse cardiac remodeling after renal denervation: Atrial electrophysiologic and structural changes associated with blood pressure lowering.

BACKGROUND: Hypertension is the most common modifiable risk factor associated with atrial fibrillation. OBJECTIVE: The purpose of this study was to determine the effects of blood pressure (BP) lowering after renal denervation on atrial electrophysiologic and structural remodeling in humans. METHODS: Fourteen patients (mean age 64 ± 9 years, duration of hypertension 16 ± 11 years, on 5 ± 2 antihypertensive medications) with treatment-resistant hypertension underwent baseline 24-hour ambulatory BP monitoring, echocardiography, cardiac magnetic resonance imaging, and electrophysiologic study. Electrophysiologic study included measurements of P-wave duration, effective refractory periods, and conduction times. Electroanatomic mapping of the right atrium was completed using CARTO3 to determine local and regional conduction velocity and tissue voltage. Bilateral renal denervation was performed, and all measurements repeated after 6 months. RESULTS: After renal denervation, mean 24-hour BP reduced from 152/84 mm Hg to 141/80 mm Hg at 6-month follow-up (P < .01). Global conduction velocity increased significantly (0.98 ± 0.13 m/s to 1.2 ± 0.16 m/s at 6 months, P < .01), conduction time shortened (32 ± 5 ms to 27 ± 6 ms, P < .01), and complex fractionated activity was reduced (37% ± 14% to 19% ± 12%, P = .02). Changes in conduction velocity correlated positively with changes in 24-hour mean systolic BP (R(2) = 0.55, P = .01). There was a significant reduction in left ventricular mass (139 ± 37 g to 120 ± 29 g, P < .01) and diffuse ventricular fibrosis (T1 partition coefficient 0.39 ± 0.07 to 0.31 ± 0.09, P = .01) on cardiac magnetic resonance imaging. CONCLUSION: BP reduction after renal denervation is associated with improvements in regional and global atrial conduction and reductions in ventricular mass and fibrosis. Whether changes in electrical and structural remodeling are solely due to BP lowering or are due in part to intrinsic effects of renal denervation remains to be determined.