Magnetic resonance imaging-guided cryoballoon ablation for left atrial substrate modification in patients with atrial fibrillation.

BACKGROUND: Cryoballoon ablation (CBA) for pulmonary vein isolation (PVI) is an established modality for the treatment of atrial fibrillation (AF). We report feasibility of left atrial (LA) substrate modification in addition to PVI both using the cryoballoon. METHODS: LA substrates and CBA-induced scar were assessed at baseline and 3 months after ablation using late gadolinium enhancement magnetic resonance imaging (LGE-MRI). Common periprocedural data including postablation LGE-MRI for evaluation of esophageal thermal injury, and CBA-associated complications were collected. Freedom from AF recurrence at 12 months was assessed using Holter and 30-day rhythm monitors. RESULTS: In 26 patients (64 ± 11 years, 69% male; 27% persistent AF, CHADSVASC score: 2.3 ± 1.5; left ventricular ejection fraction: 56 ± 10%, oral anticoagulation with warfarin/direct oral anticoagulants: n = 11/15), referred for first-time AF ablation, CBA of the pulmonary veins and extrapulmonary LA substrates was performed (median: 12 [interquartile range {IQR}: 7-14] freezes over 1675 seconds [IQR: 1168-2160]). On LGE-MRI, significant postablation cryoballoon-induced LA scar (median: 19.4% [IQR: 13.4-24.7] in comparison to baseline preablation LA-LGE (median: 10.6% [IQR 3.1-13.1]; P = .01) was found. Freedom from AF recurrence at 12 months was 74.5% with median time-to-recurrence of 242 days (IQR: 172-298). In 15 of 26 (58%) patients, esophageal enhancement on the postablation MRI was present with full recovery after 3 months. No major periprocedural complications were observed. CONCLUSION: LA substrate modification in addition to PVI using LGE-MRI-guided CBA is feasible but still experimental. The efficacy and safety have to be investigated in a prospective randomized trial.

Left atrial fibrosis progression detected by LGE-MRI after ablation of atrial fibrillation.

BACKGROUND: Left atrial (LA) fibrosis is thought to be a substrate for atrial fibrillation (AF) and can be quantified by late gadolinium enhancement magnetic resonance imaging (LGE-MRI). Fibrosis formation in LA is a dynamic process and may either progress or regress following AF ablation. We examined the impact of postablation progression in LA fibrosis on AF recurrence. METHODS: LA enhancement in LGE-MRI was quantified in 127 consecutive patients who underwent first time AF ablation. Serial LGE-MRIs were done prior to AF ablation, 3 months postablation and at least 12 months after second LGE-MRI. Transient postablation lesion (TL) was defined as atrial enhancement caused by ablation lesions that was detected on the first (3 month) but not on the second postablation LGE-MRI. New fibrosis (NF) was defined as atrial enhancement detected on the most recent LGE-MRI, at least 15 months after the ablation procedure. AF recurrence and its correlation with TL and NF was assessed in all patients during the follow-up period. RESULTS: An increase of 1% NF increased the chance of postablation AF recurrence by 3% (hazard ratio [HR] 1.03, 95% CI 1-1.06, P = .05). TL had no significant impact on recurrence (P = .057). After adjusting for cardiovascular risk factors, HR increased as NF became greater. Greater volume of NF (≥21%) corresponded with lower arrhythmia-free survival (37% vs 62%, P = .01). CONCLUSION: NF formation postablation of AF is a novel marker of long-term procedural outcome. Extensive NF is associated with significantly higher risk of atrial arrhythmia recurrence.

Recurrence quantification analysis of complex-fractionated electrograms differentiates active and passive sites during atrial fibrillation.

OBJECTIVES: To differentiate electrograms representing sites of active atrial fibrillation (AF) drivers from passive ones. BACKGROUND: Ablation of complex-fractionated atrial electrograms (CFAEs) is controversial due to difficulty in distinguishing CFAEs representing sites of active AF drivers from passive mechanisms. We hypothesized that active CFAE sites exhibit repetitive wavefront directionality, thereby inscribing an electrogram conformation (Egm-C) that is more recurrent compared with passive CFAE sites; and that can be differentiated from passive CFAEs using nonlinear recurrence quantification analysis (RQA). METHODS: We developed multiple computer models of active CFAE mechanisms (ie, rotors) and passive CFAE mechanisms (ie, wavebreak, slow conduction, and double potentials). CFAE signals were converted into discrete time-series representing Egm-C. The RQA algorithm was used to compare signals derived from active CFAE sites to those from passive CFAEs sites. The RQA algorithm was then applied to human CFAE signals collected during AF ablation (n = 17 patients). RESULTS: RQA was performed in silico on simulated bipolar CFAEs within active (n = 45) and passive (n = 60) areas. Recurrence of Egm-C was significantly higher in active compared with passive CFAE sites (31.8% ± 19.6% vs 0.3% ± 0.5%, respectively, P < .0001) despite no difference in mean cycle length (CL). Similarly, for human AF (n = 39 signals), Egm-C recurrence was higher in active vs passive CFAE areas despite similar CLs (%recurrence 13.6% ± 15.5% vs 0.1% ± 0.3%, P < .002; mean CL 102.5 ± 14.3 vs 106.6 ± 14.4, P = NS). CONCLUSION: Active CFAEs critical to AF maintenance exhibit higher Egm-C recurrence and can be differentiated from passive bystander CFAE sites using RQA.

Atrial fibrosis in non-atrial fibrillation individuals and prediction of atrial fibrillation by use of late gadolinium enhancement magnetic resonance imaging.

INTRODUCTION: Besides the traditional concept of atrial fibrillation (AF) perpetuating atrial structural remodeling, there is increasing evidence that atrial fibrosis might precede AF, highlighting the need for better characterization of the fibrotic substrate. We aimed to assess atrial fibrosis by use of late gadolinium enhancement magnetic resonance imaging (LGE-MRI) in non-AF individuals and to identify predisposing risk factors. A second aim was to establish a risk score for the prevalence of AF using atrial fibrosis in addition to established clinical variables. METHODS AND RESULTS: Non-AF individuals without structural heart disease (n = 91) and matched AF controls (n = 91) underwent MRI for assessment of LGE. According to the established UTAH classification, atrial LGE ≥20% was considered extensive. Mean left atrial (LA) fibrosis in non-AF and AF individuals were 8.8 ± 6.5% and 12.5 ± 5.8%, respectively. Body mass index (BMI) >30 kg/m 2 and LA volume were predictors of atrial fibrosis. Diastolic function was not significantly different with respect to atrial fibrosis. A novel scoring system for the prevalence of AF (2 points for arterial hypertension and/or left ventricular ejection fraction <55%; 3 points for atrial fibrosis >6%) was derived demonstrating that patients in the intermediate/high-risk group had a significantly increased risk of AF. CONCLUSION: This study reports unexpectedly high atrial fibrosis in non-AF patients without apparent heart disease, highlighting the concept that structural fibrotic alterations may precede AF onset in a significant proportion of individuals. BMI as a predictor of atrial fibrosis suggests that lifestyle and drug intervention, that is, weight reduction, could positively influence fibrosis development. The derived risk score for AF prevalence provides the basis for prospective studies on AF incidence.

Management of Atrial Fibrillation in Patients with Heart Failure: Time to Implement Ablation Control.

PURPOSE OF THE REVIEW: Atrial fibrillation (AF) in patients with heart failure and reduced systolic ejection fraction (HFrEF) is common and associated with increased morbidity and mortality, and managing AF in this population has been particularly challenging with sparse data regarding the optimal treatment strategy. RECENT FINDINGS: Recent data suggests that rhythm control with catheter ablation can be of particular benefit to patients with coexisting AF and HFrEF. Recent randomized control trials actually suggest that catheter ablation could potentially improve mortality in this particular patient population. This is in stark contrast to the current practice recommendations that reserve catheter ablation for symptomatic AF in the general population. In this paper, we will review the most current randomized controlled studies using catheter ablation in HFrEF patients with the hope to increase awareness of the potential mortality benefits the need for prioritization of catheter ablation in HFrEF patients in the next AF management guidelines.

New skip parameter to facilitate recurrence quantification of signals comprised of multiple components.

Recurrence analyses are typically performed on discretized time series after applying proper embeddings, delays, and thresholds. In our study of atrial electrograms, we found limitations to this approach when sequential bipolar complexes were defined as the timings of the first two zero crosses following the initiation of each event. The reason for this is that each bipolar component consists of two points in odd-even pairings. Since recurrence analysis starts vectors on each sequential point, incorrect even-odd pairings occur for every other vector. To overcome this limitation, a new parameter SKIP is introduced such that recurrence vectors can skip 1 (or 2) points for signals with defined multiple components. To demonstrate the utility of parameter SKIP, we used the Courtemanche model to simulate the electrical activity in the human atrium on a square, two-dimensional plane with 800 × 800 nodes. Over this plane, a grid of 39 × 39 virtual unipoles was created. Neighboring unipoles formed 39 × 38 bipolar pairs, which were recorded as 1482 continuous and synchronous time series. At each unipolar site, the actual wavefront direction was determined by comparing the relative activation timings of the local intracellular potentials. Parameters were set such that the "tissue" exhibited both spiral waves (organized activity) and wave breakups (chaotic activity). For each bipolar complex in the continuous electrogram, discretized electrogram conformation was defined as the timing delays from the start of the complex to the first two zero-crosses. Long sequences of paired zero-cross timings were subjected to recurrence analysis using SKIP values of 0 (no skipping) and 1 (single skipping). Recurrence variables were computed and correlated with the absolute wavefront directions. The results showed that the introduction of the skipping window improved the correlations of some recurrence variables with absolute wavefront directions. This is critically important because such variables may be better markers for wavefront directions in human recordings when the absolute wavefront directions cannot be calculated directly.

Cardiac MRI improves identification of etiology of acute ischemic stroke.

BACKGROUND: An accurate subtype classification of acute ischemic stroke is important in clinical practice as it can greatly influence patient care in terms of acute management and devising secondary stroke prevention strategies. Approximately, one third of ischemic strokes are cryptogenic despite a comprehensive workup. Diagnostic workup for detecting cardioaortic sources of cerebral embolism commonly includes transthoracic echocardiography (TTE). However, TTE has a limited diagnostic power to detect some of the cardioaortic abnormalities and additional imaging modalities are often needed to accurately assess such abnormalities. PURPOSE: We evaluated the feasibility of cardiovascular magnetic resonance (CMR) imaging to detect the cardioaortic sources of ischemic stroke. METHODS: A total of 106 patients were included, of which 85 had an ischemic stroke and 21 had a transient ischemic attack (TIA). Routine diagnostic workup (RDW) included brain diffusion-weighted image MRI, telemetry, magnetic resonance angiography/CT angiography of head and neck, carotid duplex ultrasonography, laboratory studies and TTE. Patients additionally underwent CMR. Subtype assignment was performed in accordance with the Stop Stroke Study of the Trial of Org 10172 in Acute Stroke Treatment classification system by a stroke neurologist after reviewing the admission notes and diagnostic test results. A second subtype classification was assigned with an additional criterion defined based on delayed enhancement (DE)-CMR findings. Additionally, the presence of non-coronary artery disease (CAD) scarring was assessed in ischemic stroke patients and compared with the TIA patients as the control group. RESULTS: RDW detected cardioaortic embolism (CAE) stroke in 32 (37.6%) patients and cryptogenic stroke in 23 patients (27.1%). Addition of CMR resulted in a 26.1% reduction in the rate of cryptogenic strokes (6 patients). Furthermore, DE-CMR findings allowed for reclassification of three additional cryptogenic subtypes, resulting in a 39.1% reduction of cryptogenic stroke rate. Non-CAD scarring was detected in 13 (15.3%) stroke patients as opposed to only 1 (4.8%) TIA patient. CONCLUSIONS: CMR is a valuable tool for the detection of CAE sources in patients with cryptogenic ischemic stroke and provides clinicians with a unique set of information that may substantially change the long-term management of these patients. DE-CMR also detects non-CAD scarring, which may indicate a predisposition to ischemic stroke. Further studies with larger samples and long-term follow-up are needed to further evaluate the clinical significance of our findings.

Saturation recovery-prepared magnetic resonance angiography for assessment of left atrial and esophageal anatomy.

OBJECTIVES: Magnetic resonance angiography (MRA) has been established as an important imaging method in cardiac ablation procedures. In pulmonary vein (PV) isolation procedures, MRA has the potential to minimize the risk of severe complications, such as atrio-esophageal fistula, by providing detailed information on esophageal position relatively to cardiac structures. However, traditional non-gated, first-pass (FP) MRA approaches have several limitations, such as long breath-holds, non-uniform signal intensity throughout the left atrium (LA), and poor esophageal visualization. The aim of this observational study was to validate a respiratory-navigated, ECG-gated (EC), saturation recovery-prepared MRA technique for simultaneous imaging of LA, LA appendage, PVs, esophagus, and adjacent anatomical structures. METHODS: Before PVI, 106 consecutive patients with a history of AF underwent either conventional FP-MRA (n = 53 patients) or our new EC-MRA (n = 53 patients). Five quality scores (QS) of LA and esophagus visibility were assessed by two experienced readers. The non-parametric Mann-Whitney U-test was used to compare QS between FP-MRA and EC-MRA groups, and linear regression was applied to assess clinical contributors to image quality. RESULTS: EC-MRA demonstrated significantly better image quality than FP-MRA in every quality category. Esophageal visibility using the new MRA technique was markedly better than with the conventional FP-MRA technique (median 3.5 [IQR 1] vs median 1.0, p < 0.001). In contrast to FP-MRA, overall image quality of EC-MRA was not influenced by heart rate. CONCLUSION: Our ECG-gated, respiratory-navigated, saturation recovery-prepared MRA technique provides significantly better image quality and esophageal visibility than the established non-gated, breath-holding FP-MRA. Image quality of EC-MRA technique has the additional advantage of being unaffected by heart rate. ADVANCES IN KNOWLEDGE: Detailed information of cardiac anatomy has the potential to minimize the risk of severe complications and improve success rates in invasive electrophysiological studies. Our novel ECG-gated, respiratory-navigated, saturation recovery-prepared MRA technique provides significantly better image quality of LA and esophageal structures than the traditional first-pass algorithm. This new MRA technique is robust to arrhythmia (tachycardic, irregular heart rates) frequently observed in AF patients.

Late Gadolinium Enhancement Magnetic Resonance Imaging Evaluation of Post-Atrial Fibrillation Ablation Esophageal Thermal Injury Across the Spectrum of Severity.

Background Esophageal thermal injury (ETI) is a byproduct of atrial fibrillation (AF) ablation using thermal sources. The most severe form of ETI is represented by atrioesophageal fistula, which has a high mortality rate. Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) allows identification of ETI. Hence, we sought to evaluate the utility of LGE-MRI as a method to identify ETI across the entire spectrum of severity. Methods and Results All AF radiofrequency ablations performed at the University of Utah between January 2009 and December 2017 were reviewed. Patients with LGE-MRI within 24 hours following AF ablation as well as patients who had esophagogastroduodenoscopy in addition to LGE-MRI were identified. An additional patient with atrioesophageal fistula who had AF ablation at a different institution and had MRI and esophagogastroduodenoscopy at the University of Utah was identified. A total of 1269 AF radiofrequency ablations were identified. ETI severity was classified on the basis of esophageal LGE pattern (none, 60.9%; mild, 27.5%; moderate, 9.9%; severe, 1.7%). ETI resolved in most patients who underwent repeat LGE-MRI at 3 months. All patients with esophagogastroduodenoscopy-confirmed ETI had moderate-to-severe LGE 24 hours after ablation MRI. Moderate-to-severe LGE had 100% sensitivity and 58.1% specificity in detecting ETI, and a negative predictive value of 100%. Atrioesophageal fistula was visualized by both computed tomography and LGE-MRI in one patient. Conclusions LGE-MRI is useful in detecting and characterizing ETI across the entire severity spectrum. LGE-MRI exhibits an extremely high sensitivity and negative predictive value in screening for ETI after AF ablation.

Treatment of Atrial Fibrillation in Patients with Co-existing Heart Failure and Reduced Ejection Fraction: Time to Revisit the Management Guidelines?

AF in patients with heart failure and reduced ejection fraction (HFrEF) is common and is associated with an increased risk of stroke, heart failure hospitalisation and all-cause mortality. Rhythm control of AF in this population has been traditionally limited to the use of antiarrhythmic drugs. Clinical trials assessing superiority of pharmacological rhythm control over rate control have been largely disappointing. Catheter ablation has emerged as a viable alternative to pharmacological rhythm control in symptomatic AF and has enjoyed significant technological advancements over the past decade. Recent clinical trials have suggested that catheter ablation is superior to pharmacological interventions in patients with co-existing AF and HFrEF. In this article, we will review the therapeutic options for AF in patients with HFrEF in the context of the latest clinical trials beyond the current established guidelines.

High-Power Radiofrequency Catheter Ablation of Atrial Fibrillation: Using Late Gadolinium Enhancement Magnetic Resonance Imaging as a Novel Index of Esophageal Injury.

OBJECTIVES: This study retrospectively evaluated the feasibility and esophageal thermal injury (ETI) patterns of high-power short-duration (HPSD) radiofrequency atrial fibrillation (AF) ablation. BACKGROUND: ETI following AF ablation can lead to serious complications. Little consensus exists on the optimal radiofrequency power setting or on the optimal strategy to assess ETI. METHODS: A total of 687 patients undergoing first-time AF ablation with either HPSD ablation (50 W for 5 s, n = 574) or low-power long-duration ablation (LPLD, ≤35 W for 10 to 30 s, n = 113) were analyzed. ETI was assessed by late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) within 24 h post-ablation. Patients with moderate or severe esophageal LGE had a follow-up MRI within 24 h to 1 week, and esophagogastroduodenoscopies were performed when significant gastrointestinal symptoms or persistent LGE on repeat MRI was present. AF recurrence adjusted for potential confounders was analyzed. RESULTS: The average age was 69.0 ± 11.8 years in the group undergoing HPSD ablation versus 68.3 ± 11.6 years in the LPLD group (p = 0.554), with 67.1% versus 59.3% male (p = 0.111). Esophageal LGE patterns were similar (64.8% vs. 57.5% none, 21.0% vs. 28.3% mild, 11.5% vs. 11.5% moderate, 2.8% vs. 2.7% severe for HPSD vs. LPLD, respectively; p = 0.370) with no atrioesophageal fistulas. Mean procedure length was significantly shorter in the HPSD group (149 ± 65 min vs. 251 ± 101 min; p < 0.001). AF recurrence rates were similar in the 2 groups for the mean 2.5-year follow-up period (adjusted, 42% vs. 41%; p = 0.571). CONCLUSIONS: HPSD ablation results in similar ETI patterns, as assessed by same-day LGE MRI, compared with the LPLD setting but with significantly shorter procedure times. Recurrence rates at 2.5-year follow-up are similar.

A method for quantifying recurrent patterns of local wavefront direction during atrial fibrillation.

INTRODUCTION: Spiral wave reentry is a potential mechanism of atrial fibrillation (AF), but is difficult to differentiate clinically from multiple wavelet breakup using standard bipolar recordings. We developed a new methodology using bipolar recordings to estimate the direction of local activation wavefronts during AF by calculating the electrogram conformation (Egm-C). We subsequently used recurrence quantification analysis (RQA) of Egm-C to differentiate regions of spiral wave reentry from wavelet breakup. METHODS: A 2D computer simulation was created with regions containing a stable spiral wave and also regions of wavebreak. A grid of 40 × 40 unipolar electrodes was superimposed. At each site, the actual wavefront direction (WD) was determined by comparing relative activation timings of the local intracellular recordings, and the estimated wavefront direction (Egm-C) was determined from the morphology of the local bipolar electrogram. RQA of Egm-C was compared to RQA of actual WD in order to differentiate AF mechanisms. RESULTS: RQA of actual WD and Egm-C both distinguished regions of spiral wave reentry from wavelet breakup with high correlation between the two methods (recurrence rate, r = 0.96; determinism, r = 0.61; line max, r = 0.95; entropy, r = 0.84; p < 0.001 for all). In areas of stable spiral wave reentry, the recurrence plots of both Egm-C and actual WD demonstrated stable, periodic dynamics, while regions of wavelet breakup demonstrated chaotic behavior largely devoid of repetitive activation patterns. CONCLUSION: Calculation of Egm-C allows RQA to be performed on bipolar electrograms during AF and differentiates regions of spiral wave reentry from multiple wavelet breakup.

Management of ventricular tachycardia in heart failure.

Ventricular tachyarrhythmias are common in patients with congestive heart failure. The clinical presentation ranges from an asymptomatic incidental electrocardiographic finding to palpitations, syncope, and sudden cardiac death. Although implantable cardioverter defibrillators successfully prevent sudden cardiac death associated with ventricular fibrillation and ventricular tachycardia, recurrent implantable cardioverter defibrillators shocks remain a clinical management challenge. In this review, we discuss management strategies of ventricular tachycardia in congestive heart failure, including drug therapy, radiofrequency catheter ablation (RFCA), and recent RFCA advances.

Safety of MRIs in patients with pacemakers and defibrillators.

With a burgeoning population, increases in life expectancy, and expanding indications, the number of patients with cardiac devices such as pacemakers and implantable cardioverter defibrillators continues to increase each year. A majority of these patients will develop an indication for magnetic resonance imaging (MRI) in their lifetime. MRIs have established themselves as one of the most powerful imaging tools for a variety of conditions. However, given the historic safety concerns, many physicians are reluctant to use MRIs in this patient population. In this paper, we discuss the potential adverse effects of MRIs in patients with cardiac devices, review key studies that have addressed strategies to limit adverse effects, and provide our cardiovascular MRI laboratory's protocol for imaging patients with implanted cardiac devices.

Bidirectional ventricular tachycardia: ping pong in the His-Purkinje system.

BACKGROUND: Bidirectional ventricular tachycardia (BVT), which is characterized by an alternating beat-to-beat ECG QRS axis, is a rare but intriguing arrhythmia associated with digitalis toxicity, familial catecholaminergic polymorphic ventricular tachycardia (CPVT), and several other conditions that predispose cardiac myocytes to delayed afterdepolarizations (DADs) and triggered activity. Evidence from human and animal studies attributes BVT to alternating ectopic foci originating from the distal His-Purkinje system in the left and/or right ventricle, respectively. OBJECTIVE: The purpose of this study was to evaluate a simple "ping pong" model of reciprocating bigeminy to explain BVT. METHODS: We constructed a two-dimensional anatomic model of the rabbit ventricles with a simplified His-Purkinje system, in which different sites in the His-Purkinje system had different heart rate thresholds for DAD-induced bigeminy. RESULTS: When the heart rate exceeded the threshold for bigeminy at the first site in the His-Purkinje system, ventricular bigeminy developed, causing the heart rate to accelerate and exceed the threshold for bigeminy at the second site. Thus, the triggered beat from the first site induced a triggered beat from the second site. The triggered beat from the second site next reciprocated by inducing a triggered beat from the first site, and so forth. Bigeminy from two sites produced BVT, and that from three or more sites produced polymorphic VT. CONCLUSION: This "ping pong" mechanism of reciprocating bigeminy readily produces the characteristic ECG pattern of BVT and its degeneration to polymorphic VT if additional sites develop bigeminy.