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INTRODUCTION Management of persistent atrial fibrillation (PersAF) remains challenging, and many patients are left on medical therapy after a failed first ablation. In patients with recurrent symptomatic arrhythmias after PersAF ablation, we aimed to compare outcomes of repeat ablation and medical therapy versus medical therapy alone. METHODS AND RESULTS All 682 consecutive patients with recurrent symptomatic arrhythmia after a first ablation for PersAF at our institution (2005-2012) were included. Repeat ablation with continuation of medical therapy was performed in 364 patients (Group 1) and 318 were only medically managed (Group 2). The outcome of interest was freedom from arrhythmia recurrence beyond a 3-month blanking period. Separate analyses were performed to assess this endpoint totally off antiarrhythmics (primary endpoint) or alternatively with/without use of antiarrhythmics (secondary endpoint). Over a median follow-up of 26 months, 41.5% of Group 1 patients met the primary endpoint and remained free from arrhythmia recurrence off antiarrhythmics (vs. 14.5% in Group 2, P

Objectives The aim of this study was to evaluate the prognostic value of quantitative assessment of pericardial delayed hyperenhancement (DHE) among patients with recurrent pericarditis (RP). Background Pericardial DHE on cardiac magnetic resonance may persist beyond the acute phase of pericarditis, suggesting continued pericardial inflammation. Methods This is a retrospective cohort study of 159 patients with RP who underwent DHE imaging and had a follow-up period of more than 6 months. Pericardial inflammation was quantified on short-axis DHE sequences by contouring the pericardium, selecting normal septal myocardium as a reference region, and then quantifying the pericardial signal that was >6 SD above the reference. Our primary outcome was clinical remission; secondary outcomes were time to recurrence and recurrence rate. Results The mean age of our patients was 46 ± 14 years, and 52% were women. During a median follow-up period of 23 months (interquartile range: 15 to 34 months), 32 (20%) patients achieved clinical remission. In the multivariable Cox proportional hazards model, lower quantitative pericardial DHE (hazard ratio: 0.77; 95% confidence interval: 0.64 to 0.93; p = 0.008) was independently associated with clinical remission. When added to background clinical and laboratory variables, quantitative pericardial DHE had incremental prognostic value over baseline clinical and laboratory variables (integrated discrimination improvement: 8%; net reclassification improvement: 36%). Furthermore, patients with a higher quantitative DHE had shorter time to subsequent recurrence (p = 0.012) and had a higher recurrence rate at 6 months (p = 0.026). Conclusions Quantitative assessment of pericardial DHE was associated with clinical outcomes among patients with RP and provided incremental information regarding the clinical course of patients with RP.

Body size is a tightly regulated phenotype in metazoans that is dependent on both intrinsic and extrinsic factors. While signaling pathways such as insulin, Hippo, and myostatin are known to control organ and body size, the downstream effectors that mediate their effects are still poorly understood. In the nematodeC. elegans, a Bone Morphogenetic Protein (BMP)-related signaling pathway is the major regulator of growth and body size. DBL-1, the BMP-related ligand, is secreted by neurons and body wall muscle, and acts as a dose-dependent regulator of body size. We investigated the transcriptional network through which the DBL-1/BMP pathway regulates body size and identified cuticle collagen genes as major effectors of growth control. Here we demonstrate that cuticle collagen genes can act as positive regulators (col-41), dose-sensitive regulators (rol-6), and negative regulators (col-141, col-142) of body size. Moreover, we show requirement of DBL-1/BMP signaling for stage-specific expression of cuticle collagen genes. We used chromatin immunoprecipitation followed by high throughput sequencing (ChIP-Seq) and electrophoretic mobility shift assays to show that the Smad signal transducers directly associate with conserved Smad binding elements in regulatory regions ofcol-141andcol-142, but not ofcol-41.Hence, cuticle collagen genes are directly and indirectly regulated via the DBL-1/BMP pathway. These results provide the first direct regulatory link between this conserved signaling pathway and the collagen genes that act as its downstream effectors in body size regulation. Since collagen mutations and misregulation are implicated in numerous human genetic disorders and injury sequelae, understanding how collagen gene expression is regulated has broad implications.Author SummaryBody size in humans and other animals is determined by the combined influence of genetic and environmental factors. Failure to regulate growth and body size appropriately can lead to a variety of functional impairments and reduced fitness. Progress has been made in identifying genetic determinants of body size, but these have not often been connected into functional pathways. In the nematode modelCaenorhabditis elegans,single gene mutations in the BMP signaling pathway have profound effects on body size. Here we have elucidated the BMP transcriptional network and identified cuticle collagen genes as downstream effectors of body size regulation through the BMP pathway. Collagens play diverse roles in biology; mutations are often associated with rare heritable diseases such as osteogenesis imperfecta and Ehlers-Danlos syndrome. Our work thus connects a conserved signaling pathway with its critical downstream effectors, advancing insight into how body size is specified.

ObjectivesRecurrences of pericarditis (RP) are often difficult to diagnose due to lack of clinical signs and symptoms during subsequent episodes. We aimed to investigate the value of quantitative assessment of pericardial delayed hyperenhancement (DHE) in diagnosing ongoing recurrences of pericarditis.MethodsQuantitative DHE was measured in 200 patients with established diagnosis of RP using cardiac MRI. Conventional clinical criteria for diagnosis of pericarditis were ≥2 of the following: chest pain, pericardial rub, ECG changes and new or worsening pericardial effusion.ResultsA total of 67 (34%) patients were identified as having ongoing episode of recurrence at the time of DHE measurements. In multivariable analysis, chest pain (OR: 10.9, pConclusionAmong patients with RP, quantitative DHE provided incremental information to diagnose ongoing recurrences over conventional clinical criteria of pericarditis. Quantitative DHE demonstrated acceptable test characteristics to diagnose ongoing recurrence even in RP patients presenting with chest pain.

Cognitive impairment (CI) is an inclusive term to describe trouble with memory, learning, concentration, or decision-making. CI is highly prevalent in patients with heart failure (HF) and is known to be associated with a variety of poor outcomes. While published HF guidelines recommend screening for CI, they do not indicate how, due to a lack of consensus in the literature about which instrument to use. Our recommendation is to use the Mini-Cog for this purpose because of its brevity and utility in identifying patients with HF at high risk for hospitalization or mortality. At this time, there is minimal published clinical trial evidence about how to manage CI in patients with HF. Reasonable approaches to management may include following guideline-directed medical therapy for HF, treatment of hypertension and atrial fibrillation, management of depression, proactive diagnosis and treatment of sleep apnea, and encouragement of aerobic exercise and weight loss. Left ventricular assist device (LVAD) therapy in patients with Stage D HF may improve CI in the short term after implantation, though there is a risk of worsening CI in the intermediate and long term. Clinicians who care for patients with HF should routinely screen for CI and when identified should encourage interventions to support self-care, increase family involvement, and arrange for more frequent follow-up.

Background: In patients with a left ventricular ejection fraction (LVEF) ≤ 35%, randomized clinical trials have demonstrated the benefit of implantable cardioverter defibrillators (ICDs) in the primary prevention of sudden cardiac death. However, the modality for LVEF assessment was not mandated

Organismal growth and body size are influenced by both genetic and environmental factors. We have utilized the strong molecular genetic techniques available in the nematode Caenorhabditis elegans to identify genetic determinants of body size. In C. elegans, DBL-1, a member of the conserved family of secreted growth factors known as the Transforming Growth Factor β superfamily, is known to play a major role in growth control. The mechanisms by which other determinants of body size function, however, is less well understood. To identify additional genes involved in body size regulation, a genetic screen for small mutants was previously performed. One of the genes identified in that screen was sma-21. We now demonstrate that sma-21 encodes ADT-2, a member of the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family of secreted metalloproteases. ADAMTS proteins are believed to remodel the extracellular matrix and may modulate the activity of extracellular signals. Genetic interactions suggest that ADT-2 acts in parallel with or in multiple size regulatory pathways. We demonstrate that ADT-2 is required for normal levels of expression of a DBL-1-responsive transcriptional reporter. We further demonstrate that adt-2 regulatory sequences drive expression in glial-like and vulval cells, and that ADT-2 activity is required for normal cuticle collagen fibril organization. We therefore propose that ADT-2 regulates body size both by modulating TGFβ signaling activity and by maintaining normal cuticle structure.