Hypertension and atrial fibrillation: Evidence of progressive atrial remodeling with electrostructural correlate in a conscious chronically instrumented ovine model
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.
Available from: Scott Willoughby
- "Furthermore, pre-clinical work has shown a relationship between short-term hypertension and increased atrial inflammation leading to a substrate for AF . The atrial remodeling process in the same hypertensive model was progressive, highlighting the potential benefits of early treatment to prevent formation of an arrhythmogenic substrate . Taken together, aortic stiffness may identify a subset of at-risk patients in the pre-hypertensive spectrum. "
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ABSTRACT: Recent community-based research has linked aortic stiffness to the development of atrial fibrillation. We posit that aortic stiffness contributes to adverse atrial remodeling leading to the persistence of atrial fibrillation following catheter ablation in lone atrial fibrillation patients, despite the absence of apparent structural heart disease. Here, we aim to evaluate aortic stiffness in lone atrial fibrillation patients and determine its association with arrhythmia recurrence following radio-frequency catheter ablation.
We studied 68 consecutive lone atrial fibrillation patients who underwent catheter ablation procedure for atrial fibrillation and 50 healthy age- and sex-matched community controls. We performed radial artery applanation tonometry to obtain central measures of aortic stiffness: pulse pressure, augmentation pressure and augmentation index. Following ablation, arrhythmia recurrence was monitored at months 3, 6, 9, 12 and 6 monthly thereafter.
Compared to healthy controls, lone atrial fibrillation patients had significantly elevated peripheral pulse pressure, central pulse pressure, augmentation pressure and larger left atrial dimensions (all P<0.05). During a mean follow-up of 2.9±1.4 years, 38 of the 68 lone atrial fibrillation patients had atrial fibrillation recurrence after initial catheter ablation procedure. Neither blood pressure nor aortic stiffness indices differed between patients with and without atrial fibrillation recurrence. However, patients with highest levels (≥75(th) percentile) of peripheral pulse pressure, central pulse pressure and augmentation pressure had higher atrial fibrillation recurrence rates (all P<0.05). Only central aortic stiffness indices were associated with lower survival free from atrial fibrillation using Kaplan-Meier analysis.
Aortic stiffness is an important risk factor in patients with lone atrial fibrillation and contributes to higher atrial fibrillation recurrence following catheter ablation procedure.
Available from: Wiek H van Gilst
- "This study was designed to investigate atrial remodeling occurring in diseases preceding AF. In large animal models of hypertension, atrial remodeling including atrial dilatation, cellular hypertrophy, fibrosis and inflammation and increased AF inducibility have been described , . However, small animal models are more useful to investigate the effect of specific genes on the AF substrate . "
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ABSTRACT: Atrial fibrillation (AF) is often preceded by underlying cardiac diseases causing ventricular pressure overload.
It was our aim to investigate the progression of atrial remodeling in a small animal model of ventricular pressure overload and its association with induction of AF.
Male mice were subjected to transverse aortic constriction (TAC) or sham operation. After four or eight weeks, echocardiographic measurements and hemodynamic measurements were made and AF induction was tested. The hearts were either fixed in formalin or ventricles and atria were separated, weighed and snap-frozen for RNA analysis.
Four weeks of pressure overload induced ventricular hypertrophy and minor changes in the atria. After eight weeks a significant reduction in left ventricular function occurred, associated with significant atrial remodeling including increased atrial weight, a trend towards an increased left atrial cell diameter, atrial dilatation and increased expression of markers of hypertrophy and inflammation. Histologically, no fibrosis was found in the left atrium. But atrial gene expression related to fibrosis was increased. Minor changes related to electrical remodeling were observed. AF inducibility was not different between the groups. Left ventricular end diastolic pressures were increased and correlated with the severity of atrial remodeling but not with AF induction.
Permanent ventricular pressure overload by TAC induced atrial remodeling, including hypertrophy, dilatation and inflammation. The extent of atrial remodeling was directly related to LVEDP and not duration of TAC per se.
Available from: link.springer.com
- "Angiotensin II is a well characterized profibrotic molecule, giving rise to atrial fibrosis and conduction heterogeneity . Lau and colleagues  have confirmed that hypertension is associated with early and progressive changes in atrial remodeling. Atrial remodeling occurs at different time domains in chronic hypertension with significant electro-structural correlation of the remodeling cascade. "
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Recently, catheter-based renal sympathetic denervation (RSD) has been verified to be safely used to substantially reduce the levels of blood pressure, left ventricular hypertrophy, sleep apnea severity and norepinephrine spillover, and improve glucose tolerance. All these pathological changes are recognized as independent risk factors for the development and recurrence of atrial fibrillation (AF). A randomized, single-blind, parallel-control, multicenter clinical trial is being conducted to compare RSD with antiarrhythmic drugs (AAD) in patients with drug-resistant hypertension and symptomatic AF (RSDforAF trial).
Patients with drug-resistant hypertension and symptomatic AF will be randomized to RSD and the drug treatment groups. Patients will be followed for 12 months until study closure. Up to 200 patients may be enrolled in six medical centers in China. The primary objective is to study the effects of RSD on AF burden and blood pressure in patients with hypertension and symptomatic AF.
RSDforAF trial will test the hypothesis that RSD is superior to AAD in reducing AF burden and blood pressure in patients with drug-resistant hypertension and symptomatic AF.
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