Atrial Fibrillation in Kidney Failure: Challenges in Risk Assessment and Anticoagulation Management.

Management of atrial fibrillation (AF) is a clinical conundrum in people with kidney failure. Stroke risk is disproportionately high, but clinicians have a limited armamentarium to improve outcomes in this population in whom there is a concurrently high bleeding risk. Direct oral anticoagulants may have a superior benefit-risk profile compared with vitamin K antagonists in people on hemodialysis. Although research has predominantly focused on identifying a safe and effective oral anticoagulation option to reduce stroke risk in people with kidney failure (and predominantly those on hemodialysis), it remains uncertain how clinicians discriminate between people who would derive net clinical benefit as opposed to net harm. The recommended CHA2DS2-VASc score cutoffs provide poor discriminatory value, and there is an urgent need to identify robust markers of thromboembolic risk in kidney failure. There is increasing data to challenge the prior dogma of risk equivalence across AF type, and the American Heart Association highlights moving beyond AF as a binary entity to consider the prognostic significance of AF burden. Implantable cardiac monitor studies reveal high rates and varied burden of subclinical and paroxysmal AF in people on hemodialysis. The association between AF burden and the proarrhythmic environment of hemodialysis with cyclical volume loading, offloading, and electrolyte changes is not well studied. We review the significance of AF burden as a contributor to thromboembolic risk, its potential as the missing link in risk assessment, and updated evidence for anticoagulation in people with kidney failure.

Absence of late gadolinium enhancement on cardiac magnetic resonance imaging in ventricular fibrillation and nonischemic cardiomyopathy.

INTRODUCTION: Cardiac magnetic resonance (CMR)-identified late gadolinium enhancement (LGE), representing regional fibrosis, is often used to predict ventricular arrhythmia risk in nonischemic cardiomyopathy (NICM). However, LGE is more closely correlated with sustained monomorphic ventricular tachycardia (SMVT) than ventricular fibrillation (VF). We characterized CMR findings of ventricular LGE in VF survivors. METHODS: We examined consecutively resuscitated VF survivors undergoing contrast-enhanced 1.5T CMR between 9/2007 and 7/2016. We excluded coronary artery disease, hypertrophic cardiomyopathy, amyloid, sarcoid, arrhythmogenic right ventricular cardiomyopathy, and channelopathy. Preexisting implantable cardioverter-defibrillator (ICD) was a CMR contraindication. VF patients were divided into three groups: (1) NICM, (2) left ventricular (LV) dilatation with normal LV ejection fraction (LVEF), and (3) normal LV size and LVEF. Two groups of NICM patients with and without SMVT were examined for comparison. RESULTS: We analyzed 87 VF patients, and found that LGE was seen in 8/22 (36%) with NICM (LVEF 38 ± 11%, LV end-diastolic volume index [LVEDVI] 134 ± 68 mL/BSA), 11/40 (28%) with LV dilatation and normal LVEF (LVEDVI 103 ± 17 mL/BSA), 4/25 (16%) with normal LV size and LVEF. Incidence of LGE in NICM patients without prior ventricular tachycardia/VF (LVEF 36 ± 12%, LVEDVI 141 ± 46 mL/body surface area [BSA]) was 117/277 and was not lower than those with VF and NICM (42% vs 36%; P = 0.59). By contrast, 22/37 NICM patients with SMVT (LVEF 42 ± 11%, LVEDVI 123 ± 48 mL/BSA) were LGE-positive (59% NICM-SMVT vs 36% NICM-VF; P = 0.04). CONCLUSION: Most VF survivors with a diagnosis of NICM did not have LGE on CMR and would not have met primary prevention ICD criteria based on LVEF. Absence of LGE may not portend a benign prognosis in NICM. Novel strategies for determining SCD risk in this cohort are required.

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.

Temporal distribution of arrhythmic events in chronic kidney disease: Highest incidence in the long interdialytic period.

BACKGROUND: Chronic kidney disease (CKD) patients undergoing hemodialysis (HD) have a high risk of sudden cardiac death (SCD). A unique risk factor may be a longer interval between HD sessions (interdialytic period). Inherent in conventional HD (thrice-weekly) are two 48-hour short breaks (SIDP) and one 72-hour long break (LIDP) between HD sessions. OBJECTIVE: We used an implantable cardiac monitor (ICM) to define the incidence and timing of significant arrhythmias in an HD population. METHODS: Fifty CKD patients undergoing HD with left ventricular ejection fraction >35% had an ICM inserted, with intensive follow-up to record SCD events and predefined bradyarrhythmias and tachyarrhythmias. RESULTS: Mean age of the patients was 67 ± 11 years; 72% were male, and the mean follow-up was 18 ± 4 months. There were 8 unexpected SCDs (16%), all during the LIDP. The terminal event was severe bradycardia with asystole in each recorded case. No episodes of polymorphic ventricular tachycardia (VT) occurred. A total of 7686 arrhythmia events were recorded in 43 patients (86%), including bradycardia in 15 patients (30%), sinus arrest in 14 (28%), second-degree atrioventricular block in 4 (8%), nonsustained VT in 10 (20%), and new-onset paroxysmal atrial fibrillation in 14 (28%). The LIDP was the highest-risk period for all arrhythmias (P < .001). The arrhythmia event rate per hour was greatest during the first pre-HD period of the week compared with any other peri-HD period (P < .001). CONCLUSION: Risk of SCD and significant arrhythmias is greatest during the LIDP. SCD was attributable to severe bradycardia and asystole. Interventions to prevent this type of SCD or shorten the LIDP deserve further evaluation. CLINICAL TRIAL REGISTRATION INFORMATION: URL: https://www.anzctr.org.au (Unique identifier: ACTRN12613001326785).

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).

Magnetic resonance post-contrast T1 mapping in the human atrium: validation and impact on clinical outcome after catheter ablation for atrial fibrillation.

BACKGROUND: The impact of diffuse atrial fibrosis detected by T1 mapping on the clinical outcome after atrial fibrillation (AF) ablation is unknown. OBJECTIVE: This study aimed to validate and assess the impact of post-contrast cardiac magnetic resonance (CMR) imaging atrial T1 mapping on the clinical outcome after catheter ablation for AF. METHODS: CMR imaging was performed in 3 groups by using a clinical 1.5-T scanner: controls, patients with paroxysmal AF, and patients with persistent AF. A T1 mapping sequence was used to calculate the post-contrast T1 relaxation time (T1 time) at the interatrial septum as an index of diffuse atrial fibrosis. A subset underwent left atrial endocardial bipolar voltage mapping for electrophysiologic correlation. After AF ablation, patients underwent clinical review and 7-day Holter monitoring at 6-month intervals. RESULTS: One hundred thirty-two patients (20 controls, 71 (63%) patients with paroxysmal AF, and 41 (37%) patients with persistent AF) underwent CMR imaging. Post-contrast atrial T1 time was significantly shorter in AF groups (237 ± 42 ms) than in controls (280 ± 37 ms) (P < .001). Post-contrast atrial T1 time correlated with mean septal voltage (R2 = .48; P < .001) and global left atrial voltage (R(2) = .41; P < .001). A diagnosis of AF, AF duration, and left ventricular end-diastolic volume independently predicted shortened post-contrast atrial T1 time. The single procedure success rate was 74% at 12 ± 5 months postablation. Post-contrast atrial T1 time was the only predictor of arrhythmia recurrence in multivariate analysis (P = .015). A post-contrast atrial T1 time of >230 ms was associated with freedom from AF in 85% relative to 62% with a post-contrast atrial T1 time of <230 ms (P = .01). CONCLUSION: Post-contrast atrial T1 time as measured using CMR imaging provides an index of atrial fibrosis that correlates with tissue voltage, presence of AF, and clinical outcomes after catheter ablation.

Catheter-tissue contact force determines atrial electrogram characteristics before and lesion efficacy after antral pulmonary vein isolation in humans.

INTRODUCTION: Electrogram (EGM) characteristics are used to infer catheter-tissue contact. We examined if (a) atrial EGM characteristics predicted CF and (b) compared the value of CF versus other surrogates for predicting lesion efficacy. METHODS AND RESULTS: Twelve paroxysmal AF patients underwent pulmonary vein isolation using radiofrequency (RF) ablation facilitated by a novel CF-sensing catheter. Operators were blinded to CF. EGM amplitude, width, and morphology were measured pre- and post-RF. At each RF site, average CF, force-time integral (FTI), impedance fall, time to impedance plateau, maximum power, catheter tip temperature, and total energy delivered were recorded. An effective lesion was defined based on previously validated EGM criteria for transmural lesions. There was a moderate correlation between CF and EGM amplitude (r = 0.19) and EGM width (r = -0.22). Pre-RF, EGM amplitude, and width had modest to poor discriminative capacity for identifying preablation CF (e.g., EGM amplitude identified CF>20 g with sensitivity and specificity of 67% and 60%, respectively). Preablation CF, FTI, and total energy delivered during RF were the only independent predictors of effective lesion formation. Neither pre-RF EGM amplitude/width nor power, temperature, and impedance changes during RF predicted effective lesion formation. An average CF >16 g or FTI >404 g*s had excellent sensitivity and specificity (>80%) for identifying an effective lesion. CONCLUSIONS: EGM characteristics do not reliably predict either CF before the onset of RF, nor do they predict the likelihood of an effective lesion. CF parameters were superior to power, temperature, and impedance changes during RF in predicting lesion efficacy.

Pulmonary vein isolation: the impact of pulmonary venous anatomy on long-term outcome of catheter ablation for paroxysmal atrial fibrillation.

BACKGROUND: Circumferential pulmonary vein (PV) isolation is the cornerstone of catheter ablation for atrial fibrillation (AF); however, PV reconnection remains problematic. OBJECTIVE: To assess the impact of PV anatomy on outcome after AF ablation. METHODS: One hundred two patients with paroxysmal AF underwent cardiac magnetic resonance (60%) or computed tomography (40%) before AF ablation. PV anatomy was classified according to the presence of common PVs, accessory PVs, PV branching pattern, and the dimensions of the PV ostia, intervenous ridges (IVRs), and the left PV-left atrial appendage ridge. RESULTS: Four discrete PVs were present in 48(47%) of the patients: a left common PV in 38(37%), a right common PV in 2(2%), an accessory right PV in 20(20%), and left PV in 4(4%). At a mean follow-up of 12 ± 4 months, 75 of 102 (74%) patients were free of recurrent AF. A LCPV was associated with an increase in freedom from AF (87% vs 66% for 4 PV anatomy; P = .03). Greater left IVR length (16.9 ± 3.5 mm vs 14.0 ± 3.0 mm; P ≤ .001) and width (1.4 ± 0.6 mm vs 1.1 ± 0.6 mm; P = .02) were associated with increased AF recurrence. After multivariate analysis, abnormal anatomy (LCPV or accessory PV) and left IVR length were found to be the only independent predictors of freedom from AF. CONCLUSIONS: Four discrete PVs are present in the minority of patients with paroxysmal AF undergoing PV isolation. The presence of a LCPV is associated with an increased freedom from AF after catheter ablation. PV anatomy may in part explain the variable outcome to electrical isolation in patients with paroxysmal AF.

Characterization of catheter-tissue contact force during epicardial radiofrequency ablation in an ovine model.

BACKGROUND: Contact force (CF) during radiofrequency ablation (RFA) is an important determinant of endocardial lesion size with limited data on epicardial RFA and CF. We evaluated CF characteristics using irrigated RFA on the epicardium in an ovine model. METHODS AND RESULTS: In 12 sheep, a 7-F irrigated RFA catheter with CF sensor was introduced via a pericardial incision onto/in parallel with ventricular epicardium. RFA (30 W per 30 second duration) was applied at 5g, 10g, 20g, 40g, and 70g: (1) over left and right ventricular myocardium with or without fat, (2) either directly over or adjacent to a coronary artery, or directly over the phrenic nerve. Force-time integral, lesion dimensions, and coronary artery/phrenic nerve injury were recorded. Lesion size, volume, and force-time integral progressively increased with higher CF (P<0.05). Steam pops occurred with high CF. Epicardial fat had an attenuating effect on RF penetration into myocardium (P<0.05); however, myocardial RF lesions could be created at sites with >3.5 mm epicardial fat. At sites with epicardial fat, each 10g increment in CF led to a 0.6 mm increase in lesion depth, whereas each 1 mm of fat reduced lesion depth into underlying myocardium by 0.7 mm. Extent of acute coronary injury with direct and indirect RFA and phrenic nerve palsy occurrence was proportional to CF. CONCLUSIONS: CF is a determinant of epicardial RF lesion size, steam pops, acute coronary artery injury, and phrenic nerve injury. Although epicardial fat limits lesion size, RFA with high CF can produce small myocardial RF lesions at sites of thick epicardial fat.

Effects of high dose intravenous fish oil on human atrial electrophysiology: implications for possible anti- and pro-arrhythmic mechanisms in atrial fibrillation.

BACKGROUND: Intravenous omega-3 polyunsaturated fatty acids (ω-3 PUFAs) may prevent atrial fibrillation (AF) inducibility and perpetuation in animal models. We examined the effect of high dose IV ω-3 PUFAs on human atrial electrophysiology. METHODS AND RESULTS: We randomised 88 patients with no structural heart disease to receive saline (control group) or high dose IV ω-3 PUFA infusion prior to detailed atrial electrophysiologic evaluation. Biologically active components, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were measured in total lipids, free fatty acid and phospholipid (membrane incorporated) fraction pre and post infusion. Compared to pre-infusion values, EPA and DHA increased significantly in the total lipids and free fatty acid but were unchanged in the phospholipid fraction. IV ω-3 did not alter atrial refractory periods, however it slowed right, left and global atrial conduction (P<.05). Inducible AF was significantly less likely in ω-3 patients compared to controls (AF ≥ 5 min, 20% vs. 58%, P = .02) and was non-sustained (mean AF duration: 14s vs. 39 s, P<.001), however inducible and sustained atrial flutter was more common (≥ 5 min: 28% vs. 0%, P = .01). Organisation of AF into flutter was observed in a greater proportion of inductions in the ω-3 group (8.5% vs. 0.6%, P<.001). CONCLUSIONS: IV ω-3 PUFAs (as free fatty acids) cause acute atrial conduction slowing, suppress AF inducibility, organise AF into atrial flutter and enhance atrial flutter inducibility. These findings provide a novel insight into potential anti and pro-arrhythmic mechanisms of fish oils in human AF.

Predictive value of impedance changes for real-time contact force measurements during catheter ablation of atrial arrhythmias in humans.

BACKGROUND: Catheter-tissue contact force (CF) determines radiofrequency (RF) ablation lesion size. Impedance changes during RF delivery are used as surrogate markers for CF. The relationship between impedance and real-time CF in humans remains unknown. OBJECTIVES: To determine whether impedance changes have predictive value for real-time CF during catheter ablation of atrial arrhythmias. METHODS: Real-time CF, force-time integral, and impedance were measured in 2265 RF lesions for atrial fibrillation or flutter in 34 patients. Operators were blinded to CF measurements. Impedance preablation, at 5-second intervals for 30 seconds after the RF onset, maximal impedance fall and time to impedance plateau during RF were correlated with CF. Average CF was divided into low (≤20 g), intermediate (21-60 g), and high (>60 g) categories. RESULTS: Preablation impedance poorly correlated with preablation CF (R = .07). Maximal impedance fall modestly correlated with average CF and force-time integral (R = .32 and .37, respectively). There was a large degree of overlap in impedance fall between different CF categories. A maximal impedance fall of 10 Ω could predict average CF of >20 g, with a sensitivity and specificity of 71% and 53% and a positive and negative predictive value of 51% and 49%, respectively. Impedance fall was only able to differentiate between different CF categories ≥15 seconds after the RF onset. Higher CFs moderately correlated with delayed plateau in impedance (R = .41). CONCLUSIONS: Impedance measurements (both baseline and impedance fall) are, at best, moderately efficacious as surrogate markers for predicting real-time catheter-tissue CF. These findings highlight the importance of real-time CF measurements, rather than impedance changes to optimize ablation efficacy.

Left septal atrial tachycardias: electrocardiographic and electrophysiologic characterization of a paraseptal focus.

OBJECTIVE: The objective was to characterize the electrocardiographic and electrophysiological features of focal atrial tachycardia (FAT) originating from the left septum (LS). BACKGROUND: FAT is recognized to occur at predefined anatomic locations rather than randomly throughout the atria. We describe the ECG and EP features of ATs originating from the LS as an important site for apparent perinodal tachycardias. METHODS: Nine patients presenting with LS FAT from a consecutive series of 384 underwent EP/RFA for symptomatic FAT. RESULTS: The mean age was 56 ± 12 years; 7 female with symptoms for 36 ± 28 months. P wave morphology (PWM) was negative/positive in lead V1 and across the precordial leads and negative or negative/positive in inferior leads in all patients. Tachycardia was incessant in 6 out of 9 patients with a mean tachycardia cycle length 421 ± 56 milliseconds. His A was ahead of P wave in all patients (mean -15 ± 5 milliseconds) and earlier than CS proximal (mean 4 ± 9 milliseconds). Successful acute focal ablation achieved at a mean of 31 ± 12 milliseconds ahead of P wave with no recurrences at a mean follow-up of 30 ± 28 months. CONCLUSION: Although the left septum is an uncommon site for focal AT an awareness of this location for harboring foci is particularly important when mapping apparently right-sided septal tachycardias.

Effect of respiration on catheter-tissue contact force during ablation of atrial arrhythmias.

BACKGROUND: Catheter-tissue contact is important for effective lesion creation. OBJECTIVE: To assess the effect of respiration on contact force (CF) during atrial fibrillation and cavotricuspid isthmus (CTI)-dependent atrial flutter ablation. METHODS: Patients undergoing CTI ablation alone (n = 15) and pulmonary vein (PV) isolation alone (n = 12) under general anesthesia were recruited. Lesions were delivered under ventilation (30 seconds) alternating with lesions delivered under apnea (30 seconds) at an adjacent anatomical site at CTI or PV antra. The average force (F(av)), force-time integral (FTI), and force variability were measured in a region-specific manner by using a novel CF-sensing ablation catheter. Operators were blinded to CF data. RESULTS: F(av) and FTI were higher with apnea than with ventilation in all CTI and PV segments (P <.05), an effect attributed to drop in CF with each respiratory swing, resulting in greater force variability during ventilation (P <.05). Low FTI lesions (<500 g) were strongly associated with longer ablation time to achieve bidirectional CTI block (r(2) = .81; P <.001), left PVI (r(2) = .65; P = .009), and right PVI (r(2) = .41; P = .05). Sites with transient CTI block were associated with lower F(av) and FTI than were sites with persistent CTI block (P <.05). Sites of acute PV reconnection were associated with lower F(av) and FTI compared with non-reconnected sites (P <.001). CONCLUSIONS: Catheter-tissue CF is critically influenced by respiration; greater CF is observed with ablation during apnea. Poor CF is implicated in longer ablation time to achieve CTI block or PV isolation and in acute reconnection.

Stenting of unprotected left main coronary artery stenosis.

Unprotected left main stenosis greater than 50% has traditionally been managed with coronary artery bypass surgery. There is now emerging evidence to support a percutaneous strategy adopting drug-eluting stents, especially in patients at high risk for surgery. This paper will review recent outcomes of both bare-metal and drug-eluting stent use for unprotected left main stenosis and summarise results of an Australian registry. Results of studies comparing the percutaneous approach to surgery will also be reviewed together with ESC and AHA/ACC current guidelines. Although percutaneous intervention of unprotected left main has been shown to be a safe and feasible procedure, unanswered questions remain. Large multi-centre randomised trials underway comparing percutaneous to surgical intervention will help clarify these ongoing issues.