Pulmonary vein isolation plus adjunctive therapy for the treatment of atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Pulmonary vein isolation (PVI) is the primary technique for ablation of atrial fibrillation (AF). It is unclear whether adjunctive therapies in addition to PVI can reduce atrial arrhythmia recurrence (AAR) compared to PVI alone in patients with AF. METHODS: A meta-analysis of randomized controlled trials comparing PVI plus an adjunctive therapy (autonomic modulation, linear ablation, non-pulmonary vein trigger ablation, epicardial PVI [hybrid ablation], or left atrial substrate modification) to PVI alone was conducted. The primary outcome was AAR. Cumulative odd's ratios (OR) and 95% confidence intervals (CI) were calculated for each treatment type. RESULTS: Forty-six trials were identified that included 8,500 participants. The mean age (± standard deviation) was 60.2 (±4.1) years, and 27.2% of all patients were female. The mean follow-up time was 14.6 months. PVI plus autonomic modulation and PVI plus hybrid ablation were associated with a relative 53.1% (OR 0.47; 95% CI 0.32 to 0.69; p < 0.001) and 59.1% (OR 0.41; 95% CI 0.23 to 0.75; p = 0.003) reduction in AAR, respectively, compared to PVI alone. All categories had at least moderate interstudy heterogeneity except for hybrid ablation. CONCLUSION: Adjunctive autonomic modulation and epicardial PVI may improve the effectiveness of PVI. Larger, multi-center randomized controlled trials are needed to evaluate the efficacy of these therapies.

Role of magnesium alone or in combination with diltiazem and/or amiodarone in prevention of atrial fibrillation following off-pump coronary artery bypass grafting.

Objectives: In this study the authors have tried to examine the role of magnesium alone or in combination with diltiazem and / or amiodarone in prevention of atrial fibrillation (AF) following off-pump coronary artery bypass grafting (CABG). Background: AF after CABG is common and contributes to morbidity and mortality. Various pharmacological preventive measures including magnesium, amiodarone, diltiazem, and combination therapy among others have been tried to lower the incidence of AF. Most of the studies have been performed in patients undergoing conventional on-pump CABG. In this uncontrolled trial, efficacy of magnesium alone or in combination with amiodarone and / or diltiazem has been studied in patients undergoing off-pump CABG. Methods: One hundred and fifty patients undergoing off-pump CABG were divided into 3 groups, Group M (n=21) received intraoperative magnesium infusion at 30mg/ kg over 1 hour after midline sternotomy; Group MD (n=78) received magnesium infusion in similar manner with diltiazem infusion at 0.05 µg/kg/hr throughout the intraoperative period; Group AMD (n=51) received preoperative oral amiodarone at a dose of 200 mg three times a day for 3 days followed by 200 mg twice daily for another 3 days followed by 200 mg once daily till the day of surgery along with magnesium and diltiazem infusion as in other groups. AF lasting more than 10 min or requiring medical intervention was considered as AF. Results: The overall incidence of postoperative AF was 12.6% with 11.7% in group AMD, 19% in group M, and 11.5% in group MD, which was not statistically significant. Conclusions: It is concluded that the use of amiodarone and/or diltiazem in addition to magnesium did not result in additional benefit of lowering the incidence of AF.

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

BACKGROUND: 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. METHODS: 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. RESULTS: Five RCTs were identified including 814 patients: 406 PVI + GP ablation and 408 PVI alone. The mean age of participants was 56.5 years 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%). CONCLUSIONS: 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.

Left Atrial Mechanical Dysfunction and the Risk for Ischemic Stroke in People Without Prevalent Atrial Fibrillation or Stroke : A Prospective Cohort Study.

BACKGROUND: Atrial myopathy-characterized by changes in left atrial function and size-may precede and promote atrial fibrillation (AF) and cardiac thromboembolism. In people without prior AF or stroke, whether analysis of left atrial function and size can improve ischemic stroke prediction is unknown. OBJECTIVE: To evaluate the association of echocardiographic left atrial function (reservoir, conduit, and contractile strain) and left atrial size (left atrial volume index) with ischemic stroke and determine whether these measures can improve the stroke prediction achieved by CHA2DS2-VASc score variables. DESIGN: Prospective cohort study. SETTING: ARIC (Atherosclerosis Risk in Communities) study. PARTICIPANTS: 4917 ARIC participants without prevalent stroke or AF. MEASUREMENTS: Ischemic stroke events (2011 to 2019) were adjudicated by physicians. Left atrial strain was measured using speckle-tracking echocardiography. RESULTS: Over 5 years, the cumulative incidences of ischemic stroke in the lowest quintiles of left atrial reservoir, conduit, and contractile strain were 2.99% (95% CI, 1.89% to 4.09%), 3.18% (CI, 2.14% to 4.22%), and 2.15% (CI, 1.09% to 3.21%), respectively, and that of severe left atrial enlargement was 1.99% (CI, 0.23% to 3.75%). On the basis of the Akaike information criterion, left atrial reservoir strain plus CHA2DS2-VASc variables was the best predictive model. With the addition of left atrial reservoir strain to CHA2DS2-VASc variables, 11.6% of the 112 participants with stroke after 5 years were reclassified to higher risk categories and 1.8% to lower risk categories. Among the 4805 participants who did not develop stroke, 12.2% were reclassified to lower and 12.7% to higher risk categories. Decision curve analysis showed a predicted net benefit of 1.34 per 1000 people at a 5-year risk threshold of 5%. LIMITATION: Underascertainment of subclinical AF. CONCLUSION: In people without prior AF or stroke, when added to CHA2DS2-VASc variables, left atrial reservoir strain improves stroke prediction and yields a predicted net benefit, as shown by decision curve analysis. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute of the National Institutes of Health.

Non-pharmacologic autonomic neuromodulation for treatment of heart failure: A systematic review and meta-analysis of randomized controlled trials.

Treatment strategies that modulate autonomic tone through interventional and device-based therapies have been studied as an adjunct to pharmacological treatment of heart failure with reduced ejection fraction (HFrEF). The main objective of this study was to perform a meta-analysis of randomized controlled trials which evaluated the efficacy of device-based autonomic modulation for treatment of HFrEF. All randomized-controlled trials testing autonomic neuromodulation device therapy in HFrEF were included in this trial-level analysis. Autonomic neuromodulation techniques included vagal nerve stimulation (VNS), baroreflex activation (BRA), spinal cord stimulator (SCS), and renal denervation (RD). The prespecified primary endpoints included mean change and 95% confidence intervals (CI) of left ventricular ejection fraction (LVEF), NT pro-B-type natriuretic peptide (NT-proBNP), and quality of life (QOL) measures including 6-minute hall walk distance (6-MHWD), and Minnesota Living with Heart Failure Questionnaire (MLHFQ). New York Heart Association (NYHA) functional class improvement was reported as odds ratios and 95% CI of improvement by at least 1 functional class. Eight studies were identified that included 1037 participants (2 VNS, 2 BRA, 1 SCS, and 3 RD trials). This included 6 open-label, 1 single-blind, and 1 sham-controlled, double-blind study. The mean age (±SD) was 61 (±9.3) years. The mean follow-up time was 7.9 months. Twenty percent of the total patients were female, and the mean BMI (±SD) was 29.86 (±4.12). Autonomic neuromodulation device therapy showed a statistically significant improvement in LVEF (4.02%; 95% CI 0.24,7.79), NT-proBNP (-219.80 pg/ml; 95% CI -386.56, -53.03), NYHA functional class (OR 2.32; 95% CI 1.76, 3.07), 6-MHWD (48.39 m; 95% CI 35.49, 61.30), and MLHFQ (-12.20; 95% CI -19.24, -5.16) compared to control. In patients with HFrEF, the use of autonomic neuromodulation device therapy is associated with improvement in LVEF, reduction in NT-proBNP, and improvement in patient-centered QOL outcomes in mostly small open-label trials. Large, double-blind, sham-controlled trials designed to detect differences in hard cardiovascular outcomes are needed before widespread use and adoption of autonomic neuromodulation device therapies in HFrEF.

External validation of Chronic Pancreatitis Prognosis Score (COPPS): A prospective cohort study.

BACKGROUND: Prognostic stratification in ChronicPancreatitis(CP) remains suboptimal and cumbersome. Chronic Pancreatitis Prognostic Score(COPPS) was recently developed to predict one-year hospitalisations in CP. AIM: External validation of COPPS in a geographically divergent patient population. METHODS: A single-center prospective cohort study, conducted on out-patients of a tertiary-care hospital. Consecutive adults with CP were assessed for COPPS risk predictors at baseline, similar to the original development cohort, and followed for one-year for: 1)hospitalisations; 2)development of pancreatitis-related complications; and 3)need for endoscopic and/or surgical interventions. Outcomes were compared by Kendall's tau-b(τb) and other statistical tests. Only those who had complete one-year follow-up were included in analysis. RESULTS: There were 177 patients(mean±SD age: 35.9 ± 11.2 years), 116(65%) males and 117(66%) with Idiopathic CP. Despite being younger, with significantly more females and Idiopathic CP, than the original development cohort, our cohort was similar to the latter regarding COPPS severity at baseline. Eight patients died over one-year; 169 were evaluated for outcomes. Increasingly severe COPPS categories correlated with increasing number of hospitalisations(both overall and pancreatitis-related) and increasing number of days spent in hospital(both overall and pancreatitis-related) irrespective of age at symptoms-onset(≤35 vs >35years), etiology(idiopathic vs alcohol) and smoking-status. CONCLUSIONS: COPPS is effective in a geographically distinct cohort having a different case-mix of CP patients(ClincialTrials.gov ID:NCT04907266).

Abnormal P-wave terminal force in lead V1 is associated with low left atrial appendage ejection velocity.

BACKGROUND: Sinus P-wave abnormalities have been associated stroke in people with atrial fibrillation (AF). The majority of AF-related strokes occur from left atrial appendage (LAA) thromboembolism. Dysfunction of the left atrium (LA) and left atrial appendage (LAA) can increase rates of thromboembolic stroke. We studied whether abnormal P wave terminal force in V1 (aPTFV1) is associated with decreased LAA ejection velocity (LAAV) on transesophageal echocardiography (TEE). METHODS: We conducted a retrospective cross-sectional study reviewing patients at a tertiary care medical center who underwent TEE in sinus rhythm and had an interpretable sinus ECG within 12 months of TEE. Participants were excluded for complex congenital heart disease, age <18, cardiac transplantation, and chronic atrial pacing. Logistic regression analysis was used to estimate the odds ratios of LAAV<40 cm/s for aPTFV1. RESULTS: In our final cohort of 169 patients (28% of which had LAAV <40), the multivariate odds ratio of aPTFV1 for LAAV<40 cm/s after adjustment for CHA2DS2VASc variables, heart rate during TEE, history of atrial arrhythmias, and left atrial volume index was 2.24 (95% CI of 1.13-6.00). CONCLUSION: Abnromal P-wave terminal force in lead V1 is associated with low LAAV after adjustment for potential confounders. Future research is needed for validation of our findings and determination of clinical utility.

Frequent Premature Atrial Contractions Are Associated With Poorer Cognitive Function in the Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: To evaluate the association of premature atrial contraction (PAC) frequency with cognitive test scores and prevalence of dementia or mild cognitive impairment (MCI). MATERIALS AND METHODS: We conducted a cross-sectional analysis using Atherosclerosis Risk in Communities study visit 6 (January 1, 2016, through December 31, 2017) data. We included 2163 participants without atrial fibrillation (AF) (age mean ± SD, 79±4 years; 1273 (58.9%) female; and 604 (27.97.0% Black) who underwent cognitive testing and wore a leadless, ambulatory electrocardiogram monitor for 14 days. We categorized PAC frequency based on the percent of beats: less than 1%, minimal; 1% to <5%, occasional; greater than or equal to 5%, frequent. We derived cognitive domain-specific factor scores (memory, executive function, language, and global z-score). Dementia and MCI were adjudicated. RESULTS: During a mean analyzable time of 12.6±2.6 days, 339 (15.7%) had occasional PACs and 107 (4.9%) had frequent PACs. Individuals with frequent PACs (vs minimal) had lower executive function factor scores by 0.30 (95% CI, -0.46 to -0.14) and lower global factor scores by 0.20 (95% CI, -0.33 to -0.07) after multivariable adjustment. Individuals with frequent PACs (vs minimal) had higher odds of prevalent dementia or MCI after multivariable adjustment (odds ratio, 1.74; 95% CI, 1.09 to 2.79). These associations were unchanged with additional adjustment for stroke. CONCLUSION: In community-dwelling older adults without AF, frequent PACs were cross-sectionally associated with lower executive and global cognitive function and greater prevalence of dementia or MCI, independently of stroke. Our findings lend support to the notion that atrial cardiomyopathy may be a driver of AF-related outcomes. Further research to confirm these associations prospectively and to elucidate underlying mechanisms is warranted.

Association of Ventricular Arrhythmias With Dementia: The Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: We performed a cross-sectional analysis to determine whether nonsustained ventricular tachycardia (NSVT) and premature ventricular contractions (PVCs) were associated with dementia in a population-based study. METHODS: We included 2,517 (mean age 79 years, 26% Black) participants who wore a 2-week ambulatory continuous ECG recording device in 2016 to 2017. NSVT was defined as a wide-complex tachycardia ≥4 beats with a rate >100 bpm. We calculated NSVT and PVC burden as the number of episodes per day. Dementia was adjudicated by experts. We used logistic regression to assess the associations of NSVT and PVCs with dementia. RESULTS: The mean recording time of the Zio XT Patch was 12.6 ± 2.6 days. There were 768 (31%) participants with NSVT; prevalence was similar in White and Black participants. There were 134 (6.5%) dementia cases (5% in White, 10% in Black participants). After multivariable adjustment, there was no overall association between NSVT and dementia; however, there was a significant race interaction (p < 0.001). In Black participants, NSVT was associated with a 3.67 times higher adjusted odds of dementia (95% confidence interval [CI] 1.92-7.02) compared to those without NSVT, whereas in White participants NSVT was not associated with dementia (odds ratio [95% CI] 0.64 [0.37-1.10]). In Black participants only, a higher burden of PVCs was associated with dementia. CONCLUSIONS: Presence of NSVT and a higher burden of NSVT and PVCs are associated with dementia in elderly Black people. Further research to confirm this novel finding and to elucidate the underlying mechanisms is warranted.

Association of Abnormal P-Wave Indices With Dementia and Cognitive Decline Over 25 Years: ARIC-NCS (The Atherosclerosis Risk in Communities Neurocognitive Study).

Background Abnormal P-wave indices (PWIs)-reflecting underlying left atrial abnormality-are associated with increased risk of stroke independent of atrial fibrillation. We assessed whether abnormal PWIs are associated with incident dementia and greater cognitive decline, independent of atrial fibrillation and ischemic stroke. Methods and Results We included 13 714 participants (mean age, 57±6 years; 56% women; 23% black) who were followed for dementia through the end of 2015. (Abnormal P-wave terminal force in lead V1, ≥4000 µV×ms), abnormal P-wave axis (>75° or <0°), prolonged P-wave duration (>120 ms), and advanced interatrial block were determined from ECGs at visits 2 to 4. Dementia was adjudicated by an expert panel using data from cognitive tests and hospitalization International Classification of Diseases codes. Cognitive function was measured longitudinally using 3 neuropsychological tests. Cox proportional hazards models were used to assess the association between time-dependent abnormal PWIs with incident dementia. Linear regression models were used to evaluate PWIs with cognitive function over time. At the conclusion of the study, 19%, 16%, 28%, and 1.9% of participants had abnormal P-wave terminal force in lead V1, abnormal P-wave axis, prolonged P-wave duration, and advanced interatrial block, respectively. During mean follow-up of 18 years, there were 1390 (10%) dementia cases. All abnormal PWIs except advanced interatrial block were associated with an increased risk of dementia even after adjustment for incident atrial fibrillation and stroke: multivariable hazard ratio of abnormal P wave terminal force in lead V1=1.60, 95% CI, 1.41 to 2.83; abnormal P-wave axis, hazard ratio =1.36, 95% CI, 1.17 to 2.57; prolonged P-wave duration, hazard ratio=1.60, 95% CI, 1.42 to 1.80. Only abnormal P-wave terminal force in lead V1 was associated with greater decline in global cognition. Conclusions Abnormal PWIs are independently associated with an increased risk of dementia. This novel finding should be replicated in other cohorts and the underlying mechanisms should be evaluated.

Septal Versus Lateral Mitral Isthmus Ablation for Treatment of Mitral Annular Flutter.

OBJECTIVES: This study sought to compare efficacy and safety of the septal mitral isthmus line (SMIL) with that of the lateral mitral isthmus line (LMIL) for treatment of mitral annular flutter (MAF). BACKGROUND: MAF is the most common left atrial macro-re-entrant organized atrial tachycardia (OAT) occurring after catheter ablation of atrial fibrillation. The 2 most common lesion sets for treating MAF include linear ablation from the anteroseptal mitral annulus to the right superior pulmonary vein (SMIL) and from the lateral mitral annulus to left inferior pulmonary vein (LMIL). METHODS: The study included all mitral isthmus ablations performed at the Hospital of the University of Pennsylvania in 2016 and 2017. Acute procedural results and long-term arrhythmia-free survival were compared between groups. RESULTS: Of 114 total MILs, conduction block was achieved across 73 (93.6%) SMILs compared with 29 (80.6%) LMILs (p = 0.05). Although the length of the SMIL was longer (48.9 ± 12.8 cm vs. 38.7 ± 12.8 cm; p = 0.001), time required to achieve block was shorter (25.2 ± 15.9 min vs. 36.6 ± 21.3 min; p = 0.03). Coronary sinus ablation was required in 58.3% of LMILs due to inability to achieve conduction block with left atrial ablation alone. In multivariate analysis, only failure to achieve acute MIL block remained significantly associated with subsequent OAT recurrence (hazard ratio: 6.39; 95% confidence interval: 1.37 to 29.9; p = 0.02). CONCLUSIONS: The SMIL requires less time to complete and more frequently results in acute MIL block than the LMIL. Additionally, ablation is rarely required outside the left atrium. Failure to achieve acute MIL block is strongly associated with subsequent OAT recurrence.