Hypertension and atrial fibrillation: evidence of progressive atrial remodeling with electrostructural correlate in a conscious chronically instrumented ovine model.
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.
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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; · 4.17 Impact Factor
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ABSTRACT: In the last few years, n-3 polyunsaturated acids (PUFAs) have been extensively studied for the prevention of AF, mostly in patients without heart failure (HF) or LV dysfunction. This post-hoc analysis of the GISSI-HF trial assessed the effect of n-3 PUFAs on AF in patients with chronic HF without AF at study entry over a median follow-up of 3.9 years. In the GISSI-HF trial, 6975 patients with chronic HF were randomized to 1 g daily of n-3 PUFAs or placebo on top of recommended therapy for HF. Of these, 1140 (16.3%) had AF at baseline ECG and were excluded from the present analysis. AF during the trial was defined as the presence of AF on the ECGs done at each visit during the trial or AF as a cause of worsening HF or hospital admission or as an event during hospitalization. Dietary fish consumption and the circulating levels of n-3 PUFAs (the latter in a subset of 1203 patients) were also available. Among the 5835 patients without AF at study entry, 444 randomized to n-3 PUFAs (15.2%) and 408 to placebo (14.0%) developed AF (unadjusted hazard 1.10, P = 0.19). Lower circulating n-3 PUFA levels were independently associated with higher AF prevalence at study entry, but not with its new occurrence. Despite an inverse relationship between plasma n-3 PUFA levels and prevalent AF, this study found no evidence that 1 g daily n-3 PUFA supplementation in patients with chronic HF reduces incident AF.European Journal of Heart Failure 07/2013; 15(11). · 5.25 Impact Factor
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ABSTRACT: Atrial fibrillation (AF) is the most common arrhythmia (estimated lifetime risk, 22%-26%). The aim of this article is to review the clinical epidemiological features of AF and to relate them to underlying mechanisms. Long-established risk factors for AF include aging, male sex, hypertension, valve disease, left ventricular dysfunction, obesity, and alcohol consumption. Emerging risk factors include prehypertension, increased pulse pressure, obstructive sleep apnea, high-level physical training, diastolic dysfunction, predisposing gene variants, hypertrophic cardiomyopathy, and congenital heart disease. Potential risk factors are coronary artery disease, kidney disease, systemic inflammation, pericardial fat, and tobacco use. AF has substantial population health consequences, including impaired quality of life, increased hospitalization rates, stroke occurrence, and increased medical costs. The pathophysiology of AF centers around 4 general types of disturbances that promote ectopic firing and reentrant mechanisms, and include the following: (1) ion channel dysfunction, (2) Ca(2+)-handling abnormalities, (3) structural remodeling, and (4) autonomic neural dysregulation. Aging, hypertension, valve disease, heart failure, myocardial infarction, obesity, smoking, diabetes mellitus, thyroid dysfunction, and endurance exercise training all cause structural remodeling. Heart failure and prior atrial infarction also cause Ca(2+)-handling abnormalities that lead to focal ectopic firing via delayed afterdepolarizations/triggered activity. Neural dysregulation is central to atrial arrhythmogenesis associated with endurance exercise training and occlusive coronary artery disease. Monogenic causes of AF typically promote the arrhythmia via ion channel dysfunction, but the mechanisms of the more common polygenic risk factors are still poorly understood and under intense investigation. Better recognition of the clinical epidemiology of AF, as well as an improved appreciation of the underlying mechanisms, is needed to develop improved methods for AF prevention and management.Circulation Research 04/2014; 114(9):1453-68. · 11.09 Impact Factor