Early ablation of newly diagnosed paroxysmal atrial fibrillation (NEWPaAF) versus newly diagnosed persistent atrial fibrillation (NEWPeAF): Comparison of patient populations and ablation outcomes.

INTRODUCTION: Little is known about very early atrial fibrillation (AF) ablation after first AF detection. METHODS: We evaluated patients with AF ablation <4 months from newly diagnosed paroxysmal AF (NEWPaAF) and newly diagnosed persistent AF (NEWPeAF). We compared the two patient populations and compared ablation outcomes to those undergoing later ablation. RESULTS: Ablation was done <4 months from AF diagnosis in 353 patients (135 = paroxysmal, 218 = persistent). Early ablation outcome was best for NEWPaAF versus NEWPeAF for initial (p = 0.030) but not final (p = 0.102) ablation. Despite recent AF diagnosis in both groups, they were clinically quite different. NEWPaAF patients were younger (64.3 ± 13.0 vs. 67.3 ± 10.9, p = 0.0020), failed fewer drugs (0.39 vs. 0.60, p = 0.007), had smaller LA size (4.12 ± 0.58 vs. 4.48 ± 0.59 cm, p < 0.0001), lower BMI (28.8 ± 5.0 vs. 30.3 ± 6.0, p = 0.016), and less CAD (3.7% vs. 11.5%, p = 0.007), cardiomyopathies (2.2% vs. 22.9%, p = 0.0001), hypertension (46.7% vs. 67.4%, p < 0.0001), diabetes (8.1% vs. 17.4%, p = 0.011) and sleep apnea (20.0% vs. 30.3%, p = 0.031). For NEWPaAF, early ablation AF-free outcome was no better than later ablation (p = 0.314). For NEWPeAF, AF-free outcomes were better for early ablation than later ablation (p < 0.0001). Delaying ablation allowed more strokes/TIAs in both AF types (paroxysmal p = 0.014, persistent p < 0.0001). CONCLUSIONS: Patients presenting for early ablation after newly diagnosed persistent AF have more pre-existing comorbidities and worse initial ablation outcomes than patients with NEWPaAF. For NEWPaAF, there was no advantage to early ablation, as long as the AF remained paroxysmal. For NEWPeAF, early ablation gave better outcomes than later ablation and they should undergo early ablation. For both AF types, waiting was associated with more neurologic events, suggesting all patients should consider earlier ablation.

Long-Term Outcome of Patients With Idiopathic Ventricular Fibrillation: A Meta-Analysis.

BACKGROUND: The long-term outcome of the patients with idiopathic ventricular fibrillation (IVF) is not well known. METHODS AND RESULTS: Relevant studies published through May 21, 2014 were searched and identified in the MEDLINE, PsycINFO, Cochrane Library, CINAHL, and EMBASE databases and a hand search of article references was also performed. Random-effect models were used for pooling proportions of mortality and recurrent events. Twenty-three studies were included with a total of 639 patients (449 males) with a mean age ranging from 33 to 51 years. Eighty percent of patients had received ICD implantation. Over an average of 5.3 years follow-up, 167 patients (31%) experienced a recurrence of ventricular arrhythmic events (proportion, 0.29 [95% CI 0.21-0.38]). Moreover, 17 patients (3.1%) died among all studies (proportion, 0.01 [95% CI 0.00-0.04]). No association was found between the induction of sustained ventricular tachycardia or ventricular fibrillation at baseline electrophysiological study and risk of recurrent ventricular arrhythmias (risk difference: 0.12 [95% CI, 0.08-0.32]). CONCLUSIONS: In patients with IVF, this meta-analysis revealed an estimated recurrent event rate of 31% and a pooled mortality rate of 3.1% during an average of 5 years follow-up. The results of baseline electrophysiological studies are not predictive of future ventricular arrhythmias.

Association between atrial fibrillation and silent cerebral infarctions: a systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is a common cause of stroke. Silent cerebral infarctions (SCIs) are known to occur in the presence and absence of AF, but the association between these disorders has not been well-defined. PURPOSE: To estimate the association between AF and SCIs and the prevalence of SCIs in stroke-free patients with AF. DATA SOURCES: Searches of MEDLINE, PsycINFO, Cochrane Library, CINAHL, and EMBASE from inception to 8 May 2014 without language restrictions and manual screening of article references. STUDY SELECTION: Observational studies involving adults with AF and no clinical history of stroke or prosthetic valves who reported SCIs. DATA EXTRACTION: Study characteristics and study quality were assessed in duplicate. DATA SYNTHESIS: Eleven studies including 5317 patients with mean ages from 50.0 to 83.6 years reported on the association between AF and SCIs. Autopsy studies were heterogeneous and low-quality; therefore, they were excluded from the meta-analysis of the risk estimates. When computed tomography (CT) and magnetic resonance imaging (MRI) studies were combined, AF was associated with SCIs in patients with no history of symptomatic stroke (odds ratio, 2.62 [95% CI, 1.81 to 3.80]; I(2) = 32.12%; P for heterogeneity = 0.118). This association was independent of AF type (paroxysmal vs. persistent). The results were not altered significantly when the analysis was restricted to studies that met at least 70% of the maximum possible quality score (odds ratio, 3.06 [CI, 2.24 to 4.19]). Seventeen studies reported the prevalence of SCIs. The overall prevalence of SCI lesions on MRI and CT among patients with AF was 40% and 22%, respectively. LIMITATION: Most studies were cross-sectional, and autopsy studies were heterogeneous and not sufficiently sensitive to detect small lesions. CONCLUSION: Atrial fibrillation is associated with more than a 2-fold increase in the odds for SCI. PRIMARY FUNDING SOURCE: Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, Massachusetts General Hospital.

Dietary macronutrients, genetic variation, and progression of coronary atherosclerosis among women.

BACKGROUND: Previous studies observed the surprising finding that saturated fat was inversely associated with atherosclerosis progression in postmenopausal women, whereas polyunsaturated fat (PUFA) and carbohydrates were positively associated. Whether certain genes modify the association of diet with atherosclerotic progression is unknown. METHODS: Using Haplotype-tagging single nucleotide polymorphisms, we evaluated gene-diet interactions with 3 preselected genes involved in fatty acid and carbohydrate metabolism: sterol regulatory element binding protein-1 (SREBP1), insulin-induced gene-1 (INSIG1), and SREBP cleavage-activating protein (SCAP). Diet was assessed at baseline. Quantitative coronary angiography was performed at baseline and after a mean of follow-up of 3.09 years in 2,227 coronary segments in 234 postmenopausal women. RESULTS: Global effects of each gene and gene-diet interactions for different fats, total fat, and carbohydrate were evaluated. Global tests revealed no main effects between SCAP, INSIG1, and SREBP1 haplotypes and progression of atherosclerosis (P = .87, P = .58, and P = .44). After correction for 5 nutrients evaluated (Bonferroni-corrected 2-tailed α = .01), no significant gene-nutrient interactions were seen, except for a borderline global interaction between SREBP1 and PUFA intake (P interaction = .013). This interaction was specific to the G-C haplotype (frequency 35%) and was driven by n-6 rather than n-3 PUFA (P for interaction < .0001). The interaction was robust to estimated isocaloric replacement of PUFA with any other nutrient. Per each 5% energy from n-6 PUFA, a 0.21-mm greater decline in mean minimal coronary artery diameter was seen among women per each copy of the second most frequent haplotype of SREBP1. CONCLUSIONS: We observed an interaction between SREBP1 and PUFA consumption that might explain the positive association of PUFA with atherosclerosis progression in this cohort.

Cognitive impairment associated with atrial fibrillation: a meta-analysis.

BACKGROUND: Atrial fibrillation (AF) has been linked with an increased risk for cognitive impairment and dementia. PURPOSE: To complete a meta-analysis of studies examining the association between AF and cognitive impairment. DATA SOURCES: Search of MEDLINE, PsycINFO, Cochrane Library, CINAHL, and EMBASE databases and hand search of article references. STUDY SELECTION: Prospective and nonprospective studies reporting adjusted risk estimates for the association between AF and cognitive impairment. DATA EXTRACTION: Two abstracters independently extracted data on study characteristics, risk estimates, methods of AF and outcome ascertainment, and methodological quality. DATA SYNTHESIS: Twenty-one studies were included in the meta-analysis. Atrial fibrillation was significantly associated with a higher risk for cognitive impairment in patients with first-ever or recurrent stroke (relative risk [RR], 2.70 [95% CI, 1.82 to 4.00]) and in a broader population including patients with or without a history of stroke (RR, 1.40 [CI, 1.19 to 1.64]). The association in the latter group remained significant independent proof of clinical stroke history (RR, 1.34 [CI, 1.13 to 1.58]). However, there was significant heterogeneity among studies of the broader population (I2 = 69.4%). Limiting the analysis to prospective studies yielded similar results (RR, 1.36 [CI, 1.12 to 1.65]). Restricting the analysis to studies of dementia eliminated the significant heterogeneity (P = 0.137) but did not alter the pooled estimate substantially (RR, 1.38 [CI, 1.22 to 1.56]). LIMITATIONS: There is an inherent bias because of confounding variables in observational studies. There was significant heterogeneity among included studies. CONCLUSION: Evidence suggests that AF is associated with a higher risk for cognitive impairment and dementia, with or without a history of clinical stroke. Further studies are required to elucidate the association between AF and subtypes of dementia as well as the cause of cognitive impairment.

Extraluminal atherosclerosis: an under-recognised finding in human aortocoronary venous bypass grafts.

BACKGROUND: Coronary artery bypass grafting (CABG) is commonly compromised by graft atherosclerosis. Histopathologic studies confirm various forms of atherosclerosis, including positively remodelled lesions in native coronary arteries but there are no histopathologic reports of extraluminal atherosclerosis in vein grafts. METHODS: We prospectively investigated the histopathologic presence and pattern of extraluminal atherosclerosis in human old vein grafts in a two-year interval among patients undergoing redo-CABG at three university hospitals in Tehran. We separately documented clinical and angiographic findings. RESULTS: We evaluated 100 segments from 20 human old vein grafts obtained during the redo CABG. All but four segments demonstrated some degrees of luminal narrowing. Luminal atherosclerotic plaques were detectable in 61 segments. We detected extraluminal atheroscleoris in seven segments. Mean vessel wall thickness was greater in segments containing extraluminal plaques (1.41±0.26 mm versus 0.91±0.04 mm, P=0.008). Angiographic findings had a modest correlation with presence or absence of luminal atheromatous lesions (Spearman's rho: 0.331, P=0.007). Angiographic degree of stenosis could not predict the presence of positively remodelled atherosclerotic plaques (Spearman's rho: -2.21, P=0.073). CONCLUSION: Previous studies suggested positive remodelling in vein grafts. Out study provides histopathologic evidence on extraluminal atherosclerosis in human aortocoronary vein grafts.

Log-Spectral Matching GAN: PPG-based Atrial Fibrillation Detection can be Enhanced by GAN-based Data Augmentation with Integration of Spectral Loss.

Photoplethysmography (PPG) is a ubiquitous physiological measurement that detects beat-to-beat pulsatile blood volume changes and hence has a potential for monitoring cardiovascular conditions, particularly in ambulatory settings. A PPG dataset that is created for a particular use case is often imbalanced, due to a low prevalence of the pathological condition it targets to predict and the paroxysmal nature of the condition as well. To tackle this problem, we propose log-spectral matching GAN (LSM-GAN), a generative model that can be used as a data augmentation technique to alleviate the class imbalance in a PPG dataset to train a classifier. LSM-GAN utilizes a novel generator that generates a synthetic signal without a up-sampling process of input white noises, as well as adds the mismatch between real and synthetic signals in frequency domain to the conventional adversarial loss. In this study, experiments are designed focusing on examining how the influence of LSM-GAN as a data augmentation technique on one specific classification task - atrial fibrillation (AF) detection using PPG. We show that by taking spectral information into consideration, LSM-GAN as a data augmentation solution can generate more realistic PPG signals.

Very long term outcomes of atrial fibrillation ablation.

BACKGROUND: Little is known about the very long term durability of atrial fibrillation (AF) ablation. OBJECTIVE: The purpose of this study was to evaluate very long term AF ablation outcomes. METHODS: We followed 5200 patients undergoing 7145 ablation procedures. We evaluated outcomes after single and multiple ablation procedures for paroxysmal (PAF; 33.6%), persistent (PeAF; 56.4%), and long-standing (LsAF; 9.9%) AF. We compared 3 ablation eras by initial ablation catheter: early (101 patients) using solid big tip (SBT) catheters (October 2003 to December 2005), intermediate (2143 patients) using open irrigated tip (OIT) catheters (December 2005 to August 2016), and contemporary (2956 patients) using contact force (CF) catheters (March 2014 to December 2021). RESULTS: AF freedom at 5, 10, and 15 years was as follows: initial ablation: PAF 67.8%, 56.3%, 47.6%; PeAF 46.6%, 35.6%, 26.5%; and LsAF 30.4%, 18.0%, 3.4%; final ablation: PAF 80.3%, 72.6%, 62.5%; PeAF 60.1%, 50.2%, 42.5%; and LsAF 43.4%, 32.0%, 20.6%. For PAF and PeAF, CF ablation procedures were better than OIT ablation procedures (P < .0001) and both were better than SBT ablation procedures (P < .001). LsAF had no outcome improvement over the eras. The 8-year success rate after final ablation for CF, OIT, and SBT catheter eras was as follows: PAF 79.1%, 71.8%, 60.0%; PeAF 55.9%, 50.7%, 38.0%; and LsAF 42.7%, 36.2%, 31.8%. Highest AF recurrence was in the first 2 years, with a 2- to 15-year recurrence of 2%/yr. Success predictors after initial and final ablation procedures were younger age, smaller left atrium, shorter AF duration, male sex, less persistent AF, lower CHA2DS2-VASc score, fewer drugs failed, and more recent catheter era. CONCLUSION: After year 2, there is 2%/yr recurrence rate for all AF types. Ablation success is best in the CF catheter era, intermediate in the OIT era, and worst in the SBT era. Over the ablation eras, outcomes improved for PAF and PeAF but not for LsAF. We should follow patients indefinitely after ablation. We need an understanding of how to better ablate more persistent AF.

Identification of supraventricular tachycardia mechanisms with surface electrocardiograms using a convolutional neural network.

Background: It remains difficult to definitively distinguish supraventricular tachycardia (SVT) mechanisms using a 12-lead electrocardiogram (ECG) alone. Machine learning may identify visually imperceptible changes on 12-lead ECGs and may improve ability to determine SVT mechanisms. Objective: We sought to develop a convolutional neural network (CNN) that identifies the SVT mechanism according to the gold standard of SVT ablation and to compare CNN performance against experienced electrophysiologists among patients with atrioventricular nodal re-entrant tachycardia (AVNRT), atrioventricular reciprocating tachycardia (AVRT), and atrial tachycardia (AT). Methods: All patients with 12-lead surface ECG during sinus rhythm and SVT and had successful SVT ablation from 2013 to 2020 were included. A CNN was trained using data from 1505 surface ECGs that were split into 1287 training and 218 test ECG datasets. We compared the CNN performance against independent adjudication by 2 experienced cardiac electrophysiologists on the test dataset. Results: Our dataset comprised 1505 ECGs (368 AVNRT, 304 AVRT, 95 AT, and 738 sinus rhythm) from 725 patients. The CNN areas under the receiver-operating characteristic curve for AVNRT, AVRT, and AT were 0.909, 0.867, and 0.817, respectively. When fixing the specificity of the CNN to the electrophysiologist adjudicators' specificity, the CNN identified all SVT classes with higher sensitivity: (1) AVNRT (91.7% vs 65.9%), (2) AVRT (78.4% vs 63.6%), and (3) AT (61.5% vs 50.0%). Conclusion: A CNN can be trained to differentiate SVT mechanisms from surface 12-lead ECGs with high overall performance, achieving similar performance to experienced electrophysiologists at fixed specificities.

Histopathologic insight into saphenous vein bypass graft disease.

OBJECTIVES: Vein graft disease is a major drawback of coronary artery bypass grafting. However, histopathologic studies of old human aortocoronary grafts are scarce. METHODS: We screened patients undergoing redo coronary artery bypass grafting at three university hospitals and selected those with at least one excisable old vein graft. Native non-grafted saphenous veins were also obtained as controls. Clinical and angiographic data were separately documented. RESULTS: We evaluated 117 segments from 29 veins. All but 4 old graft segments showed degrees of luminal narrowing and fibrointimal proliferation. Moreover, 61 segments demonstrated atherosclerotic plaques. Such plaques were typically concentric and, compared with other segments, more frequently represented necrosis, calcification and giant cells (p < 0.001 for all comparisons) and had a higher inflammatory cell count, predominantly of lymphocytic origin. Native saphenous veins frequently showed fibrosis, but no calcification or active inflammation. Angiographic findings showed moderate correlation with the histological degree of luminal stenosis (Spearman's ρ = 0.564, p < 0.001). CONCLUSIONS: Human vein graft atherosclerosis and arterial atherosclerosis share many features; however, we found lymphocytes to be the dominant inflammatory cells within plaques. Conventional angiography underestimated the atherosclerosis burden in vein grafts. Improved understanding of disease pathophysiology could lead to the development of novel interventions that reduce costly and suboptimal repeat revascularizations.

Effect of preload reducing therapy on right ventricular size and function in patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden cardiac death in young people and athletes. To date, no treatment has proven to slow the progression of the disease. Preload reducing agents such as nitrates and diuretics have shown promising results in preventing training-induced development of ARVC in a murine model. OBJECTIVE: The purpose of this study was to describe our experience with preload reducing therapy in patients with ARVC and symptomatic right ventricular (RV) dysfunction. METHODS: We performed retrospective chart review of prospectively collected registry data and included 20 patients with definite ARVC who had serial echocardiographic measurements and an implantable cardioverter-defibrillator. Six of the 20 patients with RV end-diastolic area (RVEDA) above median (>25 cm2) and New York Heart Association functional class II-IV symptoms were successfully treated with long-term isosorbide dinitrate 5-40 mg tid (at maximum tolerated dose) and hydrochlorothiazide-spironolactone 25-25 mg daily. The main outcomes of interest were RVEDA, RV fractional area change (FAC), and RV outflow tract measurements. Generalized estimating equations with repeated measures were used to identify the association between preload reducing agents and echocardiographic structural progression. RESULTS: Patients who received preload reducing agents (n = 6) were older and had larger RVs with lower FAC at baseline. However, treatment with preload reducing agents was associated with less RVEDA enlargement during mean 3.3 (range 1-6.7) years of treatment in multivariate analysis (% change in RVEDA associated with treatment -7.71; 95% confidence interval -13.29 to -2.13; P = .007). CONCLUSION: Preload reducing agents show promising results in slowing RV enlargement in patients with ARVC and show possible disease-modifying potential.

Long-Term Electrocardiographic and Echocardiographic Progression of Arrhythmogenic Right Ventricular Cardiomyopathy and Their Correlation With Ventricular Tachyarrhythmias.

BACKGROUND: Prior studies of structural and electrocardiographic changes in arrhythmogenic right ventricular (RV) cardiomyopathy and their role in predicting ventricular arrhythmias (ventricular tachycardia) have shown conflicting results. METHODS: We reviewed 405 ECGs, 315 transthoracic echocardiographies, and 441 implantable cardioverter defibrillator interrogations in 64 arrhythmogenic RV cardiomyopathy patients (56% men, mean age [SD], 44.2 [14.6] years) over a mean follow-up of 10 (range, 2.3-19) years. Generalized estimating equations were used to identify the association between ECG abnormalities, clinical variables, and transthoracic echocardiographic measurements (>mild degree of tricuspid regurgitation, RV outflow tract diameter in parasternal long axis and short axis, RV end-diastolic area, fractional area change). RESULTS: There was a 4.65 (95% CI, 0.51%-8.8%) increase in RV end-diastolic area, a 3.75 (95% CI, 1.17%-6.34%) decrease in fractional area change, and 1.9 (95% CI, 1.3-2.8) higher odds (odds ratio) of RV wall motion abnormality with every 5-year increase in age after patients' first transthoracic echocardiography. >Mild tricuspid regurgitation was an independent predictor of RV enlargement and dysfunction (hazard ratio of >10% drop in fractional area change from baseline [95% CI], 3.51 [1.77-6.95] and hazard ratio of >10% increase in RV end-diastolic area from baseline [95% CI], 4.90 [2.52-9.52]). Patients with implantable cardioverter defibrillator were more likely to develop >mild tricuspid regurgitation and larger structural and functional disease progression. More pronounced increase in RV end-diastolic area was translated into higher rates of any ventricular tachycardia. Inferior T-wave inversions and sum of R waves (mm) in V1 to V3 were predictors of RV enlargement and dysfunction with the former also predicting risk of any ventricular tachycardia. CONCLUSIONS: Arrhythmogenic RV cardiomyopathy is a progressive disease. Tricuspid regurgitation is an independent predictor of structural disease progression, which may be exacerbated by use of a transvenous implantable cardioverter defibrillator lead.

Atrial Fibrillation and Cognitive Decline: Phenomenon or Epiphenomenon?

Atrial fibrillation is associated with cognitive impairment ranging from mild to overt dementia, and this association is independent of clinical stroke and multiple shared risk factors. Whether the use of the novel anticoagulants will offer greater protection than warfarin remains to be determined. Rate control strategies may improve brain perfusion and memory but this has not been studied in a randomized controlled trial. Overall, this is a novel field that requires multiple observational studies with long-term follow-up and large-scale randomized controlled trials with accurate neurocognitive testing and brain imaging to ultimately define effective preventive strategies and treatment options.

Contribution of Major Lifestyle Risk Factors for Incident Heart Failure in Older Adults: The Cardiovascular Health Study.

OBJECTIVES: The goal of this study was to determine the relative contribution of major lifestyle factors on the development of heart failure (HF) in older adults. BACKGROUND: HF incurs high morbidity, mortality, and health care costs among adults ≥65 years of age, which is the most rapidly growing segment of the U.S. METHODS: We prospectively investigated separate and combined associations of lifestyle risk factors with incident HF (1,380 cases) over 21.5 years among 4,490 men and women in the Cardiovascular Health Study, which is a community-based cohort of older adults. Lifestyle factors included 4 dietary patterns (Alternative Healthy Eating Index, Dietary Approaches to Stop Hypertension, an American Heart Association 2020 dietary goals score, and a Biologic pattern, which was constructed using previous knowledge of cardiovascular disease dietary risk factors), 4 physical activity metrics (exercise intensity, walking pace, energy expended in leisure activity, and walking distance), alcohol intake, smoking, and obesity. RESULTS: No dietary pattern was associated with developing HF (p > 0.05). Walking pace and leisure activity were associated with a 26% and 22% lower risk of HF, respectively (pace >3 mph vs. <2 mph; hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.63 to 0.86; leisure activity ≥845 kcal/week vs. <845 kcal/week; HR: 0.78; 95% CI: 0.69 to 0.87). Modest alcohol intake, maintaining a body mass index <30 kg/m(2), and not smoking were also independently associated with a lower risk of HF. Participants with ≥4 healthy lifestyle factors had a 45% (HR: 0.55; 95% CI: 0.42 to 0.74) lower risk of HF. Heterogeneity by age, sex, cardiovascular disease, hypertension medication use, and diabetes was not observed. CONCLUSIONS: Among older U.S. adults, physical activity, modest alcohol intake, avoiding obesity, and not smoking, but not dietary patterns, were associated with a lower risk of HF.

Pathophysiology of aortocoronary saphenous vein bypass graft disease.

Aortocoronary saphenous vein bypass grafting relieves anginal pain in patients with coronary artery disease. However, its effectiveness is limited due to graft failure; the 10-year patency rate is 50%-60%. Early, 1-year and late graft failure may be due to thrombosis, fibrointimal hyperplasia and atherosclerosis, respectively. There is general agreement that vein graft atherosclerosis differs from arterial lesions in terms of temporal and histological changes. Vein graft atherosclerosis is more rapid, with diffuse concentric changes and a less noticeable fibrous cap, making venous plaques more vulnerable to rupture and subsequent thrombus formation. Despite progress in understanding the pathophysiology, some aspects of vein graft atherosclerosis need to be clarified. This review focuses on the pathophysiologic aspects of this widespread, costly and disabling disease, with emphasis on late graft occlusion and distinctions between arterial and venous atherosclerosis in terms of histology, pathophysiology and risk factors.