A Genomic Link From Heart Failure to Atrial Fibrillation Risk: FOG2 Modulates a TBX5/GATA4-Dependent Atrial Gene Regulatory Network.

BACKGROUND: The relationship between heart failure (HF) and atrial fibrillation (AF) is clear, with up to half of patients with HF progressing to AF. The pathophysiological basis of AF in the context of HF is presumed to result from atrial remodeling. Upregulation of the transcription factor FOG2 (friend of GATA2; encoded by ZFPM2) is observed in human ventricles during HF and causes HF in mice. METHODS: FOG2 expression was assessed in human atria. The effect of adult-specific FOG2 overexpression in the mouse heart was evaluated by whole animal electrophysiology, in vivo organ electrophysiology, cellular electrophysiology, calcium flux, mouse genetic interactions, gene expression, and genomic function, including a novel approach for defining functional transcription factor interactions based on overlapping effects on enhancer noncoding transcription. RESULTS: FOG2 is significantly upregulated in the human atria during HF. Adult cardiomyocyte-specific FOG2 overexpression in mice caused primary spontaneous AF before the development of HF or atrial remodeling. FOG2 overexpression generated arrhythmia substrate and trigger in cardiomyocytes, including calcium cycling defects. We found that FOG2 repressed atrial gene expression promoted by TBX5. FOG2 bound a subset of GATA4 and TBX5 co-bound genomic locations, defining a shared atrial gene regulatory network. FOG2 repressed TBX5-dependent transcription from a subset of co-bound enhancers, including a conserved enhancer at the Atp2a2 locus. Atrial rhythm abnormalities in mice caused by Tbx5 haploinsufficiency were rescued by Zfpm2 haploinsufficiency. CONCLUSIONS: Transcriptional changes in the atria observed in human HF directly antagonize the atrial rhythm gene regulatory network, providing a genomic link between HF and AF risk independent of atrial remodeling.

Convergent epicardial-endocardial ablation for treatment of long-standing persistent atrial fibrillation: A review of literature.

BACKGROUND AND AIM OF STUDY: The convergent procedure (CVP) is a hybrid ablation technique via a subxiphoid incision that has recently emerged as a treatment option for non-paroxysmal atrial fibrillation (npAF). By combining endocardial and epicardial ablation into a simultaneous or staged procedure, the pulmonary vein and posterior left atrium can be isolated with transmural lesion sets while minimizing the risk of proarrhythmic gaps that are a known limitation with endocardial linear lesion sets. We reviewed the 12-month outcomes in patients who underwent CVP compared to those who underwent endocardial catheter ablation (CA) and surgical ablation (SA). METHODS: A literature search was conducted using the PubMed database for publications related to CVP. Selected studies included detailed 12-month follow-up of patients, patient characteristics, periprocedural complications, use of antiarrhythmic drugs (AADs), and monitoring method. RESULTS: Five studies with 340 patients who underwent CVP between January 2009 and March 2017 were selected for this review. A total of 8.5% of patients had paroxysmal AF (pAF), 42.2% had persistent AF (peAF), and 49.1% had long-standing persistent AF (lspAF). At 12 months, 81.9% of patients were in sinus rhythm, while 54.1% of patients were in sinus rhythm while not taking AADs. The overall complication rate was 10%. CONCLUSION: CVP had better 1-year efficacy in eliminating AF when compared to CA. However, SA, specifically the Cox Maze IV, had lower rates of AF recurrence in the npAF patient population. Despite its promising 1-year efficacy rates, the periprocedural complication rate for CVP was significantly higher than both CA and SA.

Challenging Management of a Patient With Severe Bilateral Deep Vein Thrombosis.

Among patients with proximal iliofemoral deep vein thrombosis (DVT) and an elevated Villalta score, anticoagulation therapy alone may not be a sufficient management strategy in select cases. In this article, we report a case of severe bilateral iliofemoral DVT that resisted the standard treatment for DVT, requiring catheter-directed thrombolysis and subsequent mechanical thrombectomy.

Food insecurity, sexual risk taking, and sexual victimization in Ghanaian adolescents and young South African adults.

OBJECTIVES: The objectives of this study were to examine whether food insecurity is associated with sexual risk taking and victimization in young people (aged 16-24); and to investigate whether the relationship of food insecurity with sexual risk taking and victimization is moderated by gender. METHODS: Cross-sectional data were obtained in 2014 from a sample of Ghanaian adolescents (n = 773) and in 2015 from young South African adults (n = 823). We used multilevel logistic regression given the study's binary outcome and clustered data. We tested a moderation effect of gender by including an interaction between gender and food insecurity. RESULTS: Food insecurity was highly prevalent (72% in Ghana and 83% in South Africa). Food insecurity was significantly associated with unwanted sexual contact among Ghanaian adolescents (OR 1.05, 95% CI 1.02, 1.08) and age-disparate sex among young South African adults (OR 1.03, 95% CI 1.00, 1.06). Results indicated no moderating effect of gender. CONCLUSIONS: Our findings underscore the importance of food access on young people's sexual health, regardless of gender. Prevention efforts may be more relevant when integrated with food security interventions that target vulnerable adolescents and young adults, irrespective of gender.