Article

Hypertension and atrial fibrillation: evidence of progressive atrial remodeling with electrostructural correlate in a conscious chronically instrumented ovine model.

Cardiovascular Research Centre, Department of Cardiology, Royal Adelaide Hospital and Discipline of Medicine, University of Adelaide, Adelaide, Australia.
Heart rhythm: the official journal of the Heart Rhythm Society (Impact Factor: 4.56). 05/2010; 7(9):1282-90. DOI: 10.1016/j.hrthm.2010.05.010
Source: PubMed

ABSTRACT Hypertension accounts for more atrial fibrillation (AF) than any other predisposing factor.
The purpose of this study was to characterize the time course, extent, and electrostructural correlation of atrial remodeling in chronic hypertension.
Thirty-two sheep were studied: 21 with induced "one-kidney, one-clip" hypertension and 11 controls. Sequential closed-chest electrophysiologic studies were performed in 12 conscious animals (6 hypertensive, 6 controls) to evaluate progressive remodeling over 15 weeks. Additional atrial structural/functional analyses were performed in 5 controls and at 5, 10, and 15 weeks of hypertension (five per time point) via histology/cardiac magnetic resonance imaging to correlate with open-chest electrophysiologic parameters.
The hypertensive group developed a progressive increase in mean arterial pressure (P <.001). Mean effective refractory periods were uniformly higher at all time points (P <.001). Progressive biatrial hypertrophy (P = .003), left atrial dysfunction (P <.05) and greater AF inducibility were seen early with increased inflammation from 5 weeks of hypertension. In contrast, significant conduction slowing (P <.001) with increased heterogeneity (P <.001) along with increased interstitial fibrosis resulted in longer and more fractionated AF episodes only from 10 weeks of hypertension. Significant electrostructural correlation was seen in conduction abnormalities and AF inducibility with both atrial inflammation and fibrosis.
Hypertension is associated with early and progressive changes in atrial remodeling. Atrial remodeling occurs at different time domains in chronic hypertension with significant electrostructural correlation of the remodeling cascade. Early institution of antihypertensive treatment may prevent formation of substrate capable of maintaining AF.

0 Bookmarks
 · 
89 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia in clinical practice. AF is often associated with profound functional and structural alterations of the atrial myocardium that compose its substrate. Recently, a relationship between the thickness of epicardial adipose tissue (EAT) and the incidence and severity of AF has been reported. Adipose tissue is a biologically active organ regulating the metabolism of neighbouring organs. It is also a major source of cytokines. In the heart, EAT is contiguous with the myocardium without fascia boundaries resulting in paracrine effects through the release of adipokines. Indeed, Activin A, which is produced in abundance by EAT during heart failure or diabetes, shows a marked fibrotic effect on the atrial myocardium. The infiltration of adipocytes into the atrial myocardium could also disorganize the depolarization wave front favouring micro re-entry circuits and local conduction block. Finally, EAT contains progenitor cells in abundance and therefore could be a source of myofibroblasts producing extracellular matrix. The study on the role played by adipose tissue in the pathogenesis of AF is just starting and is highly likely to uncover new biomarkers and therapeutic targets for AF.
    Cardiovascular research 03/2014; · 5.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The potential role of renal denervation (RD) in patients with AF and less severe hypertension is unknown. Objectives The aim of this study was to assess the potential role of RD as an adjunct to pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF) and moderate resistant or severe resistant hypertension. Methods The data for this study were obtained from two different prospective randomized studies, analyzed by meta-analysis. Patients with paroxysmal (P) AF or persistent (Pers) AF and moderate resistant hypertension (office BP ≥140/90 mm Hg and <160/100 mm Hg; first study; n=48) or severe resistant hypertension (≥160/100 mm Hg; second study; n=38) were randomized to PVI or PVI with RD. Results At 12-months, 26 of the 41 (63%) PVI with RD patients were AF-free vs 16 of the 39 (41%) patients in the PVI-only group (p=0.014). In patients with severe hypertension, 11 of the 18 (61%) PVI with RD patients vs 5 of the 18 (28%) PVI-only patients were AF-free (p=0.03). For moderate hypertension, the differences were less dramatic: 11 of 21 (52%) vs 15 of 23 (65%) when RD added (p=0.19). The superior efficacy of adding RD was most apparent in persistent AF and severe hypertension (HR 0.25 [0.09-0.72]; p=0.01). Duration of the procedure and fluoroscopy were non-significantly longer in RD group. Conclusions RD may improve the results of PVI in patients with persistent AF and/or severe resistant hypertension. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01117025 and NCT01897545.
    Heart rhythm: the official journal of the Heart Rhythm Society 01/2014; · 4.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and mortality. Currently, atrial endocardial catheter ablation, mainly targeting focal discharges in the pulmonary veins, is the most widely used interventional treatment of drug-refractory AF. Despite technical improvements, results are not yet optimal. There is ongoing search for alternative and/or complementary interventional targets. Conditions associated with increased sympathetic activation such as hypertension, heart failure and sleep apnea lead to structural, neural and electrophysiological changes in the atrium thereby contributing to the progression from paroxysmal to persistent AF and increasing recurrence rate of AF after PVI. Until now, interventional modulation of autonomic nervous system was limited by highly invasive techniques. Catheter-based renal denervation (RDN) was introduced as a minimally invasive approach to reduce renal and whole body sympathetic activation with accompanying blood pressure control and left-ventricular morphological and functional changes in resistant hypertension. This review focuses on the potential atrial antiarrhythmic and antiremodeling effects of RDN in AF patients with hypertension, heart failure, and sleep apnea and discusses the possible role of RDN in the treatment of AF.
    Clinical Research in Cardiology 03/2014; · 3.67 Impact Factor