Smaller Atria Research Articles

Quantification of atrial cardiomyopathy disease severity by electroanatomic voltage mapping and cardiac magnetic resonance imaging

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The authors acknowledge the support of the British Heart Foundation Centre for Research Excellence Award III (RE/18/5/34216). SEW is supported by the British Heart Foundation (FS/20/26/34952). Background Atrial late gadolinium enhancement (Atrial-LGE) and electroanatomic voltage mapping (Atrial-EAVM) quantify the anatomical and functional extent of atrial cardiomyopathy. Prior studies provide conflicting information relating to the level of agreement between these modalities for the assessment of atrial cardiomyopathy disease severity. Purpose We aimed to explore the relationships between, and outcomes from, these contrasting measures of atrial cardiomyopathy disease severity in patients with atrial fibrillation undergoing ablation. Methods Atrial-LGE and Atrial-EAVM was performed in patients undergoing first-time ablation for atrial fibrillation. Atrial cardiomyopathy disease severities were quantified using CEMRGApp and OpenEP[1] for Atrial-LGE and Atrial-EAVM, respectively. Correlations between modalities, their relationships with clinical features and their relationships with arrhythmia recurrence were assessed. Results Atrial-LGE and Atrial-EAVM quantification of atrial cardiomyopathy disease was performed In 123 atrial fibrillation patients (60±10 years, paroxysmal (n=58), persistent (n=65)) (Figure 1, panel A). Atrial-EAVM was moderately correlated with Atrial-LGE (r=0.41, P<0.001), with a mean fibrosis burden of 32.4±21.8% (Figure 1, panel B). The strength of the correlation was dependent on the thresholds chosen to define abnormal atrial tissue. The thresholds yielding the strongest correlation were IIR >0.97 (for Atrial-LGE) and voltage <1.17 mV (for Atrial-EAVM). Using these thresholds, agreement between modalities was strongest amongst patients in the highest tertile of fibrosis burden (mean of differences 5.9% (95% CI -30.4% to 42%)). Fibrosis burden was greater for Atrial-LGE than Atrial-EAVM (46.4±7.48% versus 13.7±7.13%, P<0.005) for patients in the lowest tertile of fibrosis burden (Figure 1, panel C). These patients were younger, had smaller atria and a greater frequency of paroxysmal atrial fibrillation than patients in the higher tertiles of fibrosis burden (Figure 2). Atrial cardiomyopathy disease severity was greater in patients with arrhythmia recurrence for both Atrial-EAVM (39.3±23.1% versus 28.5±20.2%, P=0.010) and Atrial-LGE (58.69±11.60 versus 53.33±9.63, P=0.011). In multivariable analysis, Atrial-LGE (OR 1.04 (95% CI 1.00-1.09), P=0.037) was independently associated with arrhythmia recurrence. Conclusions We demonstrate for the first time that the level of agreement between Atrial-EAVM and Atrial-LGE is dependent on the level of atrial cardiomyopathy disease severity. The functional consequences of atrial cardiomyopathy are most evident in patients with the highest anatomical extent of disease. This explains variations in prior studies and will inform future clinical applications of these techniques.

Pulmonary vein isolation with adjunctive left atrial ganglionic plexus ablation for treatment of atrial fibrillation: a meta-analysis of randomized controlled trials.

Adjunctive ganglionic plexus (GP) ablation may increase the efficacy of pulmonary vein isolation (PVI) for treatment of atrial fibrillation (AF). Prior meta-analyses examining PVI with adjunctive GP ablation have included non-randomized trials and have included trials evaluating thorascopic epicardial ablation. The objective of this study is to perform a meta-analysis of randomized controlled trials (RCTs) comparing endocardial catheter-based PVI to PVI with adjunctive GP ablation. Summary odds ratio (OR) and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed with I2 values. Sub-group analysis was performed comparing arrhythmia recurrence between patients with paroxysmal versus persistent AF at trial baseline. Meta-regressions were performed with mean left atrial diameter and left ventricular ejection fraction at trial baseline as the moderator variables. Five RCTs were identified including 814 patients: 406 PVI + GP ablation and 408 PVI alone. The mean age of participants was 56.5years and 74.7% were male. Four of these trials evaluated catheter-based endocardial ablation for a total of 574 patients: 289 PVI + GP ablation and 285 PVI alone. The odds of arrhythmia recurrence in patients undergoing adjunctive GP ablation with PVI compared with PVI alone were a reduced: odds ratio (OR) 0.58, 95% confidence interval (CI) 0.41-0.82, I2 = 40.2%. In the subgroup analysis, the odds of arrhythmia recurrence with adjunctive GP ablation were reduced in those with paroxysmal AF (OR 0.396, 95% CI 0.23-0.69, I2 = 0%). A non-significant trend to reduced arrhythmia recurrence was also observed in those with persistent AF (OR 0.726, 95% CI 0.475-1.112, I2 = 0%). When performing the meta-regression, increased left atrial diameter was associated with decreased treatment effect of adjunctive GP ablation (R2 index = 1.0, I2 = 0%). The addition of GP ablation to PVI was associated with reduced arrhythmia recurrence. Adjunctive GP ablation was more effective in paroxysmal AF and in patients with smaller atria. Larger RCTs are needed to confirm the efficacy of GP + PVI ablation.

Spironolactone affects cardiovascular and craniofacial development in zebrafish embryos (Danio rerio)

Spironolactone, a potassium-sparing diuretic and aldosterone antagonist, is a mineralocorticoid hormone commonly prescribed to patients suffering from heart failure, hirsutism, dermatological afflictions, and hypertension. Interestingly, relatively little work has been done on the development of vertebrate embryos after exposure to this compound. Here, we treat zebrafish embryos with spironolactone at 10−6 M, 10−7 M, or 10−8 M, and observe them after three to seven days of exposure. While no effect was observed in mortality, we did detect differences in cardiovascular development at 3 dpf and craniofacial development at 5 dpf. At 10−6 M, smaller atria, ventricles, and blood vessels were observed. The highest concentrations also caused a longer ceratohyal/Meckel's distance, longer palatoquadrate, and smaller angles between the palatoquadrate and both the ceratohyal and Meckel's. Further research of spironolactone’s effects on embryonic development could lead to a better understanding of the compound resulting in improved public and environmental health.

Ablation of Complex Fractionated Electrograms Improves Outcome in Persistent Atrial Fibrillation of Over 2 Year's Duration.

There is controversy and sparse data on whether substrate based techniques in addition to pulmonary vein isolation (PVI) confer benefit in the catheter ablation of persistent atrial fibrillation (AF), especially if long standing. We performed an observational study to assess whether substrate based ablation improved freedom from atrial arrhythmia. A total of 286 patients undergoing first ablation procedures for persistent AF with PVI only(n = 79), PVI plus linear ablation(n = 85), or PVI plus complex fractionated electrogram (CFAE) and linear ablation(n = 107) were followed. Primary end point was freedom from atrial arrhythmia at one year. Mean duration of pre-procedure time in AF was 28+/-27 months.There were no differences in baseline characteristics between groups except a higher proportion of patients with a severely dilated LA in those receiving PVI+CFAEs+lines. Freedom from atrial arrhythmia was higher with a PVI+CFAE+lines strategy then for PVI alone (HR 1.56, 95% CI: 1.04-2.34, p=0.032) but was not higher with PVI+lines. Benefit of substrate modification was conferred for preprocedure times in AF of over 30 months. The occurrence of atrial tachycardia was higher when lines were added to the ablation strategy (HR 0.08, 95% CI: 0.01-0.59, p=0.014). Freedom from atrial arrhythmia at 1 year was higher with lower patient age, use of general anaesthetic (GA), normal or mildly dilated left atrium and decreasing time in AF. In patients with long standing persistent AF of over 30 months duration,CFAE ablation resulted in improved freedom from atrial arrhythmia. Increased freedom from atrial arrhythmia occurs in patients who are younger and have smaller atria, and with GA procedures. Linear ablation did not improve outcome and resulted in a higher incidence of atrial tachycardia.

Catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: a systematic review and meta-analysis.

Atrial fibrillation (AF) is common in hypertrophic cardiomyopathy (HCM) and is associated with a high risk of stroke. The efficacy and safety of catheter ablation in this setting is poorly characterised. We aimed to systematically review the existing literature and to perform a meta-analysis to determine the efficacy and safety of catheter ablation of AF in patients with HCM. Random-effects meta-analysis of studies comparing HCM versus non-HCM controls. The outcomes of freedom from AF/atrial tachycardia, and acute procedure-related complications were assessed. Studies were searched on MEDLINE, EMBASE, COCHRANE and clinicaltrials.gov. Fourteen studies were considered eligible for the systematic review, of which five were included in the meta-analysis. Freedom from AF/atrial tachycardia relapse was higher in patients without HCM (after a single procedure: 38.7% HCM vs 49.8% controls, OR=2.25, 95% CI 1.09 to 4.64, p=0.03; after ≥1 procedure: 51.8% HCM vs 71.2% controls, OR=2.62, 95% CI 1.52 to 4.51, p=0.0006; I(2)=33% and 26%, respectively). Risk of procedure-related adverse events was low. Repeat procedures (mean difference=0.16, 95% CI 0.0 to 0.32, p=0.05, I(2)=53%) and antiarrhythmic drugs (OR=4.70, 95% CI 2.31 to 9.55, p<0.0001, I(2)=0%) are more frequently needed in patients with HCM to prevent arrhythmia relapse. Sensitivity analyses suggested that the outcome in patients with HCM with less dilated atria and paroxysmal AF may be more comparable to the general population. The observed complication rate of catheter ablation of AF in patients with HCM was low. Even though the risk of relapse is twofold higher, catheter ablation can be effective in patients with HCM and AF, particularly in patients with paroxysmal AF and smaller atria.

Abstract 19128: Acute Changes in Left Ventricular Contractility Following Mitraclip Implantation Depend on Left Atrial Volume

Background: The acute hemodynamic changes following elimination of mitral regurgitation is a much discussed issue, particularly in patients with severely compromised left ventricular function where the incompetent mitral valve was regarded as a pop-off valve. Herein, we investigated the acute changes of ventricular contractility in relation to left atrial volume. Methods and results: Echocardiographic left atrial and left ventricular longitudinal strain measurements before and 3 days after the procedure were performed in 19 patients (mean age: 77.9±7.9, 47% female, 73,7% functional mitral valve regurgitation, 26,3% degenerative mitral valve regurgitation) undergoing MitraClip implantation at our institution. Procedural success with reduction in MR to grade 2+ or less was achieved in all patients. Overall there was no significant change in left atrial or ventricular global or regional longitudinal strain after the procedure. However, a strong correlation was observed between worsening in left ventricular strain and left atrial volume (r: -0.72, p&lt;0.01), i.e. there was a greater reduction in left ventricular contractility after clip implantation in patients with larger left atrial volumes. Multivariate, linear regression analyses revealed that left atrial volume predicted the change of left ventricular longitudinal strain following MitraClip implantation (r2: -0.07, p&lt;0.01) independently of left ventricular ejection fraction (r2: -0.05, p=0.40), mitral regurgitant volume (r2: -0.09, p=0.09) and left atrial strain (r2: -0.03, p=0.85). Discussion: Our data suggest that enlarged left atria act as a low-resistance reservoir in mitral regurgitation. As a consequence elimination of mitral regurgitation in these patients leads to worsening of left ventricular contractility whereas in smaller atria left ventricular contractility is not negatively affected by elimination of MR.

National Heart Foundation of Australia consensus statement on catheter ablation as a therapy for atrial fibrillation

Atrial fibrillation (AF) is estimated to affect 1%-2% of the population. It is increasing in prevalence and is associated with excess mortality, considerable morbidity and hospitalisations. AF is responsible for a significant and growing societal financial burden. Catheter ablation is an increasingly used therapeutic strategy for the management of AF; however, some confusion exists among those caring for patients with this condition about the role and optimal use of ablative treatments for AF. Our aim in this consensus statement is to provide recommendations on the use of primary catheter ablation for AF in Australia, on the basis of current evidence. Our consensus is that the primary indication for catheter ablation of AF is the presence of symptomatic AF that is refractory or intolerant to at least one Class 1 or Class 3 antiarrhythmic medication. In selecting patients for catheter ablation of AF, consideration should be given to the patient's age, duration of AF, left atrial size and the presence of significant structural heart disease. Best results are obtained in younger patients with paroxysmal AF, no structural heart disease and smaller atria. Ablation techniques for patients with persistent AF are still undergoing evaluation. Discontinuation of warfarin or equivalent therapies is not considered a sole indication for this procedure. After AF ablation, anticoagulation therapy is generally recommended for all patients for at least 1-3 months. Discontinuation of warfarin or equivalent therapies after ablation is generally not recommended in patients who have a CHADS 2 score (congestive heart failure, hypertension, age ≥ 75 years, diabetes, 1 point each; prior stroke or transient ischaemic attack, 2 points) of ≥ 2.

Invited commentary

Invited commentary

Amiodarone versus propafenone for conversion of chronic atrial fibrillation: results of a randomized, controlled study

OBJECTIVESThe purpose of this study was to investigate the efficacy and safety of amiodarone and propafenone in the conversion of chronic atrial fibrillation in a prospective, randomized, placebo-controlled study.BACKGROUNDThe effectiveness of amiodarone and propafenone in the treatment of patients with chronic atrial fibrillation has not been adequately studied.METHODSOne hundred one patients (48 men, mean age 64 ± 9 years) with atrial fibrillation lasting >3 weeks participated in the study. Thirty-four patients received amiodarone (300 mg intravenously over 1 h, followed by 20 mg/kg over the next 24 h plus 600 mg orally, in three doses, for 1 week, then 400 mg/day orally, for three weeks), 32 received propafenone (2 mg/kg intravenously over 15 min, followed by 10 mg/kg over 24 h and then 450 mg/day orally, for one month) and the remaining 35 served as control subjects. All patients received digoxin and anticoagulant treatment as indicated (International Normalized Ratio 2 to 3).RESULTSConversion to sinus rhythm was achieved in 16 (47.05%) patients who received amiodarone, in 13 (40.62%) who received propafenone and in none of the control subjects (p < 0.001 for both groups vs. control subjects). Those who converted had smaller atria than those who did not and atrial fibrillation of shorter duration in both the amiodarone and propafenone groups. Treatment was discontinued in one patient of the propafenone group because of significant QRS widening.CONCLUSIONSAmiodarone and propafenone appear to be safe and equally effective in the termination of chronic atrial fibrillation. Left atrial diameter and arrhythmia duration are independent predictors of conversion.

Efficacy of amiodarone for the termination of persistent atrial fibrillation

The efficacy and safety of amiodarone in the conversion of persistent atrial fibrillation (AF) were investigated in a prospective, randomized, controlled study. Of 67 consecutive patients (32 men, mean age 64 ± 9 years) with AF lasting >48 hours, 33 received amiodarone and 34 received placebo. Baseline clinical characteristics were similar in the 2 groups. Patients randomized to amiodarone received 300 mg intravenously for 1 hour and then 20 mg/kg for 24 hours. They were also given 600 mg/day orally, divided into 3 doses, for 1 week and thereafter 400 mg/day for 3 weeks. Patients randomized to placebo received an identical amount of saline IV over 24 hours and then oral placebo for 1 month. Conversion to sinus rhythm was achieved in 16 of the 33 patients (48.5%) who received amiodarone and in none of the 34 patients in the placebo group (p <0.001). None of the patients converted to sinus rhythm within the first 3 days. Those who converted had smaller atria than those who did not (diameter 41.9 ± 7.2 vs 50.4 ± 5.7 mm, p <0.001). Sex, age, baseline heart rate, left ventricular ejection fraction, and the duration of AF did not differ significantly between patients who converted and those who did not. No side effects requiring discontinuation of treatment were observed in either group. Amiodarone, administered both intravenously and orally, appears to be safe and effective in the termination of persistent AF. Left atrial diameter is the sole independent predictor of conversion.

Restoration of sinus rhythm with flecainide in patients with atrial fibrillation

The efficacy of flecainide acetate for conversion of atrial fibrillation into sinus rhythm was assessed in 69 patients (mean age of 63 ± 14 years). Mean duration of the arrhythmia was 49 ± 45 days. Mean cardiothoracic index was 0.49 ± 0.03. Flecainide treatment was started intravenously with a bolus of 2 mg/kg over 10 minutes, followed by oral treatment (200 to 300 mg/day) according to body weight. Conversion to sinus rhythm was obtained in 49 patients (71%). The mean delay between initiation of treatment and restoration of sinus rhythm was 301 minutes (range 5 to 1,600). The left atrial diameter was smaller (40 ± 1 mm) in patients who had successful cardioversion than in those who did not (46 ± 1 mm) (p < 0.05). Patients with atrial fibrillation lasting for less than 10 days had a higher conversion rate (79%) than patients with longstanding atrial fibrillation, in whom the conversion rate was only 38% (p < 0.05). Conversion to sinus rhythm occurred in 33 patients during the first 5 minutes after injection. Adverse effects necessitated discontinuation of treatment in 4 patients (5.8%). Gastrointestinal disorders and dizziness occurred in 5 other patients but did not necessitate discontinuing treatment. In conclusion, flecainide is an effective drug for converting atrial fibrillation into sinus rhythm. Unlike quinidine, flecainide can be administered intravenously. The conversion rate with flecainide is higher in patients with a shorter duration of atrial fibrillation and smaller atria.

Marine meiobenthic Oligochaeta from Heron and Wistari Reefs (Great Barrier Reef) of the genera Clitellio, Limnodriloides and Phallodrilus (Tubificidae) and Grania (Enchytraeidae)

Marine microdrile oligochaetes are described for the first time from Eastern Australia, occurring in the sub-littoral zone beneath coral clumps on the sand flat and shallow lago on of Heron and Wistari reefs. A population density of 20,000 worms/m3, or 2 100, cm3, is estimated for Heron Reef. Clitellio arenicolus queenslandicus, subsp. nov. has proportionately smaller atria than the nominate subspecies from Naples and North America. Synonymy of C. subtilis Pierantoni with this species is questioned. Limnodriloides winckelmanni Michaelsen is described for the first time since its description for South-west African material but L. barnardi Cook, from Baja California, is regarded as a junior synonym. The genus Phallodrilus is redefined to include Torodrilus lowryi Cook, Rhyacodrilus prostatus Knollner and two new species, P. albidus and P. rohdei, and a key to the twelve species of Phallodrilus is given. Grania macrochaeta trichaeta, subsp. nov. (Enchytraeidae) is added to the three subspecies of G. macrochaeta recently recognized.