The Renin‐Angiotensin System: A Therapeutic Target in Atrial Fibrillation

Patlolla, Vishnu; Alsheikh‐Ali, Alawi A.; Al‐Ahmad, Amin

doi:10.1111/j.1540-8159.2006.00477.x

Cited by 37 publications

(24 citation statements)

References 52 publications

(101 reference statements)

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“…Only a few previous reviews have discussed the link between RAAS and arrhythmias, especially AF. [28][29][30] In this manuscript, our focus is on novel mechanisms of atrial and ventricular arrhythmia in the setting of RAAS activation.…”

Section: Introductionmentioning

confidence: 99%

The renin-angiotensin-aldosterone system (RAAS) and cardiac arrhythmias

2008

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The role of the renin-angiotensin-aldosterone system (RAAS) in many cardiovascular disorders, including hypertension, cardiac hypertrophy, and atherosclerosis is well established, whereas its relationship with cardiac arrhythmias is a new area of investigation. Atrial fibrillation and malignant ventricular tachyarrhythmias, especially in the setting of cardiac hypertrophy or failure, appear to be examples of RAAS-related arrhythmias, since treatment with RAAS modulators, including angiotensin converting enzyme inhibitors, angiotensin receptor blockers and mineralocorticoid receptor blockers, reduces the incidence of these arrhythmias. RAAS has a multitude of electrophysiological effects and can potentially cause arrhythmia through a variety of mechanisms. We review new experimental results that suggest RAAS has pro-arrhythmic effects on membrane and sarcoplasmic reticulum ion channels and that increased oxidative stress is likely contributing to the increased arrhythmic incidence. A summary of ongoing clinical trials that will address the clinical usefulness of RAAS modulators for prevention or treatment of arrhythmias is presented.

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Section: Introductionmentioning

confidence: 99%

The renin-angiotensin-aldosterone system (RAAS) and cardiac arrhythmias

2008

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“…5 In several countries, angiotensin II receptor blockers (ARBs) have attracted attention as a therapeutic drug for hypertensive individuals with AF. [6][7][8][9] However, the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE I) 10 comparing the effect of irbesartan on patients with AF (mainly persistent and permanent types) with that of placebo showed no differences between irbesartan and placebo for the recurrence of AF, indicating that ARBs did not suppress the recurrence of AF. Valsartan also did not reduce the recurrent AF rate in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation (GISSI-AF) trial.…”

mentioning

confidence: 99%

Dose Timing of an Angiotensin II Receptor Blocker/Calcium Channel Blocker Combination in Hypertensive Patients With Paroxysmal Atrial Fibrillation

Kario

Uchiyama²,

Yoshida³

et al. 2016

J of Clinical Hypertension

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It has long been thought that there is a close association between hypertension and atrial fibrillation (AF). However, the efficacy of an angiotensin II receptor blocker for the prevention of organ damage in hypertensive individuals with AF is still controversial. The present study was a multicentered, prospective, randomized, open-label clinical trial investigating the differences in the effect of treatment with telmisartan/amlodipine combination tablets on blood pressure (BP) levels and BP variability between morning and bedtime administration in hypertensive patients with paroxysmal AF, using ambulatory BP monitoring (ABPM) and home BP. With this treatment, the patients' 24-hour BP, nighttime BP, preawake BP, and morning BP shown by ABPM were significantly reduced, and the antihypertensive effects were similar regardless of the timing of the drug administration. The standard deviation of day-by-day home systolic BP and the maximum home systolic BP were also significantly reduced, and these effects were similar regardless of the treatment timing. The N-terminal pro-brain natriuretic peptide level was significantly decreased only in the bedtime administration group. A larger study will demonstrate whether the bedtime administration of telmisartan/amlodipine combination tablets maximizes the risklowering effect against AF recurrence in paroxysmal AF hypertensive patients. J Clin Hypertens (Greenwich). 2016;18:1036-1044. ª 2016 Wiley Periodicals, Inc.A close association between hypertension and atrial fibrillation (AF) has long been suspected. The Framingham Heart Study 1 showed that hypertension was an independent risk factor for incident AF in a general population, and uncontrolled elevated blood pressure (BP) was associated with an increased risk of incident AF in patients treated for hypertension.2 Based on overseas clinical trials, the main etiology of AF is hypertension in approximately 60% of AF patients.3 In addition, the Suita Study, 4 a cohort study in Japan, showed that hypertension was associated with an increased risk of incident AF.It is also suspected that hypertension not only facilitates the onset and persistence of AF, but also raises the risk of a thromboembolism. Antihypertensive treatment is therefore considered essential for hypertensive individuals with AF to prevent recurrent AF, cerebral infarction, or heart failure. 5 In several countries, angiotensin II receptor blockers (ARBs) have attracted attention as a therapeutic drug for hypertensive individuals with AF.6-9 However, the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE I) 10 comparing the effect of irbesartan on patients with AF (mainly persistent and permanent types) with that of placebo showed no differences between irbesartan and placebo for the recurrence of AF, indicating that ARBs did not suppress the recurrence of AF. Valsartan also did not reduce the recurrent AF rate in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation (GISSI-AF...

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“…Such a model is not sufficient to explain the reversal of proarrhythmic properties upon treatment with ACEIs or ARBs, suggesting other electrophysiological effects of RAAS activation. Various possible pathways have been suggested as the link underlying the relationship between RAAS and arrhythmia, especially AF [33,34].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of SERCA2a following short-term ACE inhibition (by enalaprilat) alters contractile performance and arrhythmogenicity of healthy myocardium in rat

et al. 2015

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Chronic angiotensin-converting enzyme inhibitor (ACEIs) treatment can suppress arrhythmogenesis. To examine whether the effect is more immediate and independent of suppression of pathological remodelling, we tested the antiarrhythmic effect of short-term ACE inhibition in healthy normotensive rats. Wistar rats were administered with enalaprilat (ENA, i.p., 5 mg/kg every 12 h) or vehicle (CON) for 2 weeks. Intraarterial blood pressure in situ was measured in A. carotis. Cellular shortening was measured in isolated, electrically paced cardiomyocytes. Standard 12-lead electrocardiography was performed, and hearts of anaesthetized open-chest rats were subjected to 6-min ischemia followed by 10-min reperfusion to examine susceptibility to ventricular arrhythmias. Expressions of calcium-regulating proteins (SERCA2a, cardiac sarco/endoplasmic reticulum Ca(2+)-ATPase; CSQ, calsequestrin; TRD, triadin; PLB, phospholamban; Thr(17)-PLB-phosphorylated PLB at threonine-17, FKBP12.6, FK506-binding protein, Cav1.2-voltage-dependent L-type calcium channel alpha 1C subunit) were measured by Western blot; mRNA levels of L-type calcium channel (Cacna1c), ryanodine receptor (Ryr2) and potassium channels Kcnh2 and Kcnq1 were measured by qRT-PCR. ENA decreased intraarterial systolic as well as diastolic blood pressure (by 20%, and by 31%, respectively, for both P < 0.05) but enhanced shortening of cardiomyocytes at basal conditions (by 34%, P < 0.05) and under beta-adrenergic stimulation (by 73%, P < 0.05). Enalaprilat shortened QTc interval duration (CON 78 ± 1 ms vs. ENA 72 ± 2 ms; P < 0.05) and significantly decreased the total duration of ventricular fibrillations (VF) and the number of VF episodes (P < 0.05). Reduction in arrhythmogenesis was associated with a pronounced upregulation of SERCA2a (CON 100 ± 20 vs. ENA 304 ± 13; P < 0.05) and complete absence of basal Ca(2+)/calmodulin-dependent phosphorylation of PLB at Thr(17). Short-term ACEI treatment can provide protection against I/R injury-induced ventricular arrhythmias in healthy myocardium, and this effect is associated with increased SERCA2a expression.

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The Renin‐Angiotensin System: A Therapeutic Target in Atrial Fibrillation

Cited by 37 publications

References 52 publications

The renin-angiotensin-aldosterone system (RAAS) and cardiac arrhythmias

The renin-angiotensin-aldosterone system (RAAS) and cardiac arrhythmias

Dose Timing of an Angiotensin II Receptor Blocker/Calcium Channel Blocker Combination in Hypertensive Patients With Paroxysmal Atrial Fibrillation

Upregulation of SERCA2a following short-term ACE inhibition (by enalaprilat) alters contractile performance and arrhythmogenicity of healthy myocardium in rat

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