Aldosterone blockade attenuates development of an electrophysiological substrate associated with ventricular tachyarrhythmias in heart failure

Stambler, Bruce S.; Laurita, Kenneth R.; Shroff, Sunil C.; Hoeker, Gregory S.; Martovitz, Nichole L.

doi:10.1016/j.hrthm.2009.02.005

Cited by 25 publications

(25 citation statements)

References 25 publications

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“…In vivo studies have shown that aldosterone blockers attenuate ventricular electrical remodeling and tachyarrhythmia vulnerability in different models of cardiac injury [19,55,70]. Our results suggest that aldosterone blockade reduced mortality by decreasing cardiac arrhythmia and sudden death.…”

Section: Discussionsupporting

confidence: 51%

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Aldosterone Blockade Reduces Mortality without Changing Cardiac Remodeling in Spontaneously Hypertensive Rats

Cezar

Damatto

Martinez

et al. 2013

Cell Physiol Biochem

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Background: The role of aldosterone blockers during transition from long-term compensated hypertrophy to dilated failure is not completely understood. In this study we evaluated the effects of early administration of spironolactone on cardiac remodeling, myocardial function, and mortality in spontaneously hypertensive rats (SHR). Methods: Sixteen-month-old SHR received no treatment (SHR-C, n=72) or spironolactone (SHR-SPR, 20 mg/kg/day, n=34) for six months. Echocardiogram was performed before and after treatment. Myocardial function was analyzed in left ventricular (LV) papillary muscle preparations. Myocardial collagen and hydroxyproline concentration were evaluated by morphometry and spectrophotometry, respectively. LV gene expression was assessed by real time RT-PCR. Statistics: Student's t test; Log rank test (Kaplan Meyer). Results: SHR-C and SHR-SPR presented mortality rates of 71 and 38%, respectively (p=0.004). Systolic arterial pressure did not differ between groups (SHR-C 199±43; SHR-SPR 200±35 mmHg). Initial and final echocardiograms did not show significant differences in cardiac structures or LV function between groups. Myocardial function was similar between groups at basal and after inotropic stimulation. Collagen fractional area, hydroxyproline concentration, gene expression for α- and β-myosin heavy chain, atrial natriuretic peptide, and Serca2a were not different between groups. Conclusion: Early spironolactone administration reduces mortality without changing cardiac remodeling in spontaneous hypertensive rats.

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Section: Discussionsupporting

confidence: 51%

“…In infarcted rodents, they have improved cardiac remodeling [14,15,19,53,54], whereas in dogs with rapid ventricular pacing-induced heart failure, eplerenone failed to prevent LV changes [55]. In SHR, the aldosterone blockade was evaluated during the cardiac remodeling process but not during heart failure development.…”

Section: Discussionmentioning

confidence: 99%

Aldosterone Blockade Reduces Mortality without Changing Cardiac Remodeling in Spontaneously Hypertensive Rats

Cezar

Damatto

Martinez

et al. 2013

Cell Physiol Biochem

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“…4,5 Animal studies have shown that chronic aldosterone-overload induces structural and electrical remodelling of the myocardium increasing the risk for malignant ventricular arrhythmia 24 and the use of AA attenuated electrical remodelling and suppressed the inducibility of ventricular arrhythmia. 9,25,26 The use of AA causes a delay or reversal of myocardial fibrosis as noted by a decreased turnover of extracellular markers in the treatment arm of RALES trial. 27 Spironolactone has also been shown to reduce plasma levels of metalloproteinases in ischaemic HF indicating its role in reversing collagen dysregulation that plays a role in cardiac remodelling.…”

Section: Discussionmentioning

confidence: 99%

Effect of spironolactone on ventricular arrhythmias in patients with left ventricular systolic dysfunction and implantable cardioverter defibrillators

Wase

Garikipati

Mufti

et al. 2012

Indian Heart Journal

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A B S T R A C TAims/objectives: Patients with implantable cardioverter defibrillators (ICD) often receive an adjunctive anti-arrhythmic therapy. We propose that an addition of spironolactone will reduce the number of clinically significant ventricular arrhythmias and ICD-related therapies. Methods and results:In a multicentre retrospective study, 64 patients with ischaemic and nonischaemic dilated cardiomyopathy whose left ventricular ejection fraction (LVEF) was <35% and with ICD were selected. Amongst these patients, 28 patients were on spironolactone and 36 were not taking spironolactone. The ICD interrogation data were analysed for a maximum of 12 months. Wilcoxon Rank Sum test was used to compare the study and control groups. The outcomes were: (1) the number of shocks/anti-tachycardia pacing (ATP) episodes and (2) the number of episodes of ventricular tachycardia (VT) requiring ATP, non-sustained VT (NSVT), and ventricular fibrillation (VF) over the study period. The spironolactone group had fewer monthly, VTs (P = 0.027) (requiring ATP). The two groups did not differ in the number of NSVT or VF per month.Conclusion: Addition of spironolactone as an adjunct to ICD therapy in patients with congestive heart failure (CHF) reduces VT requiring ATP, but does not affect NSVT or VF per month.

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“…Basic experimental data support these findings. Aldosterone antagonists, for example, have been shown to produce favorable effects on ventricular electrical remodeling by modifying potassium, sodium, and calcium currents and ventricular refractoriness [12][13][14] and improving the myocardial reuptake of norepinephrine. 15 They also seem to have favorable effects on ventricular structural remodeling primarily by attenuating myocardial fibrosis.…”

Section: Clinical Perspective On P 747mentioning

confidence: 99%

The Effect of Spironolactone on Ventricular Tachyarrhythmias in Patients With Implantable Cardioverter-Defibrillators

Zarraga

Dougherty

MacMurdy³

et al. 2012

Circ: Arrhythmia and Electrophysiology

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Background-Previous studies have suggested that aldosterone blockade can reduce the incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients with heart failure. The SPIronolactone to Reduce ICD Therapy (SPIRIT) trial was designed to test the hypothesis that spironolactone reduces the incidence of VT/VF in patients with implantable cardioverter-defibrillators (ICDs) who are at moderately high risk for recurrent VT/VF. Methods and Results-Ninety patients who had ICDs who were at moderately high risk for recurrent VT/VF and who were not candidates for spironolactone by current heart failure guidelines were randomized to receive spironolactone 25 mg daily or placebo in a double-blind fashion. All patients had previously received ICD therapy (shock or antitachycardia pacing) for VT/VF within 2 years of randomization or an ICD for secondary prevention of VT/VF within 6 months of randomization. The primary end point was time to first recurrence of VT/VF requiring ICD therapy. After a median follow-up of 35 months, the Kaplan-Meier probability estimates for VT/VF requiring ICD therapy were 68.7% in the placebo group and 84.7% in the spironolactone group. Compared with placebo, spironolactone was associated with a similar risk of VT/VF (hazard ratio, 1.01; 95% CI, 0.64-1.83; P=0.71). There was no significant difference between the median times to first VT/VF recurrence requiring ICD therapy in the 2 groups. Conclusions-In patients with ICDs who were at moderately high risk for recurrent VT/VF on account of a recent VT/VF event that was either sustained or treated by the ICD and who were not candidates for spironolactone by current heart failure guidelines, spironolactone did not delay the first recurrence of VT/VF or reduce the risk of recurrent VT/VF. (Circ Arrhythm Electrophysiol. 2012;5:739-747.)

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Aldosterone blockade attenuates development of an electrophysiological substrate associated with ventricular tachyarrhythmias in heart failure

Cited by 25 publications

References 25 publications

Aldosterone Blockade Reduces Mortality without Changing Cardiac Remodeling in Spontaneously Hypertensive Rats

Aldosterone Blockade Reduces Mortality without Changing Cardiac Remodeling in Spontaneously Hypertensive Rats

Effect of spironolactone on ventricular arrhythmias in patients with left ventricular systolic dysfunction and implantable cardioverter defibrillators

The Effect of Spironolactone on Ventricular Tachyarrhythmias in Patients With Implantable Cardioverter-Defibrillators

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