Ventricular arrhythmias and ARNI: is it time to reappraise their management in the light of new evidence?

Vecchi, Andrea; Abete, Raffaele; Marazzato, Jacopo; Iacovoni, Attilio; Mortara, Andrea; Ponti, Roberto De; Senni, Michele

doi:10.1007/s10741-020-09991-3

Cited by 11 publications

(9 citation statements)

References 62 publications

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“…In recent studies, ARNI proved to reduce the overall cardiovascular mortality and, more specifically, the risk of SCD in HFrEF patients. 15 Rohde et al 16 conducted a PARADIGM 2 sub-analysis (in 8399 patients), showing that sacubitril/valsartan reduced the risk of SCD in patients with an ICD [hazard ratio (HR): 0.49; 95% confidence interval (CI): 0.25–0.99] and in those who were eligible for but did not receive an ICD (HR: 0.81; 95% CI: 0.67–0.98). Moreover, Russo et al 17 studied 167 patients with dilated cardiomyopathy both with ischaemic and non-ischemic aetiology, with dual-chamber ICD on sacubitril/valsartan treatment, finding, at 12 months of follow-up, a reduction in both atrial and ventricular arrhythmias burden and an improvement in ICD electrical atrial parameters.…”

Section: Discussionmentioning

confidence: 99%

“…The precise mechanism by which ARNI may reduce SCD is not clear, however, a variety of direct and indirect hypotheses has been advanced. 15 A favourable LV reverse remodelling seems to be the main responsible mechanism, 18 as Martens et al 19 suggested after studying 151 patients with HFrEF, in whom they observed a lower degree of ventricular tachycardia or fibrillation, resulting in less ICD intervention rate, over a mean follow-up of 365 days. Also, Guerra et al 20 conducted a prospective study in a similar cohort treated with sacubitril/valsartan for 6 months, showing LV reverse remodelling and an improvement of LVEF from 28.3 ± 5.6% to 32.2 ± 6.5% ( P < 0.001), with 5.3% arrhythmias in the first 6 months of treatment with sacubitril/valsartan.…”

Section: Discussionmentioning

confidence: 99%

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Sacubitril/valsartan reduces indications for arrhythmic primary prevention in heart failure with reduced ejection fraction: insights from DISCOVER-ARNI, a multicenter Italian register

Pastore

Mandoli

Giannoni

et al. 2021

European Heart Journal Open

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Background This sub-study deriving from a multicenter Italian register (DISCOVER-ARNI) investigated whether sacubitril/valsartan in adjunction of optimal medical therapy(OMT) could reduce the rate of implantable cardioverter-defibrillator(ICD) indications for primary prevention in heart failure with reduced ejection fraction(HFrEF) according to European guidelines indications, and its potential predictors. Methods In this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centers were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical and echocardiographic data were collected at baseline and after 6 months from sacubitril/valsartan initiation. Results Of 351 patients, 225(64%) were ICD carriers and 126(36%) were not ICD carriers (of whom 13 had not indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV)EF≤35% and New York Heart Asscociation(NYHA) class=II-III, 69(60%) did not show ICD indications; 44(40%) still fulfilled ICD criteria. Age, atrial fibrillation, mitral regurgitation>moderate, left atrial volume index(LAVi), and LV global longitudinal strain(GLS) significantly varied between the groups. With ROC curves, age≥75 years, LAVi≥42ml/m2 and LV GLS≥-8.3% were associated with ICD indications persistence (AUC=0.65,=0.68,=0.68 respectively). With univariate and multivariate analysis, only LV GLS emerged as significant predictor of ICD indications at follow-up in different predictive models. Conclusions Sacubitril/valsartan may provide early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline reduced LV GLS was a strong marker of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/hemorrhagic risks and unnecessary costs deriving from ICDs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sacubitril/valsartan reduces indications for arrhythmic primary prevention in heart failure with reduced ejection fraction: insights from DISCOVER-ARNI, a multicenter Italian register

Pastore

Mandoli

Giannoni

et al. 2021

European Heart Journal Open

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“…However, as previously described, some studies report improvement in LVEF without decreasing the incidence of ventricular arrhythmias; conversely, our study showed that the number of events requiring appropriate shock decreased, despite the non-significant decrease in sustained VT or VT and the nonsignificant improvement in LVEF or LVEDD. This may suggest that the reduction of ventricular arrhythmias is only partially explained by reverse remodeling, and other mechanisms may be considered [18]. Other hypothesized mechanisms may be future investigation targets, such as the sympatholytic effect of neprilysin pathway inhibition.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Sacubitril-Valsartan on Ventricular Arrhythmia Burden in Patients With Heart Failure With Reduced Ejection Fraction

Medeiros¹,

Matta-Coelho²,

Costa-Oliveira³

et al. 2023

Cureus

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Heart failure with reduced ejection fraction (HFrEF) patients are prone to developing ventricular arrhythmias. In the PARADIGM-HF trial, sacubitril-valsartan (SV) showed a reduction in the composite endpoint of death and HF hospitalization in HFrEF patients; subgroup analysis of this trial revealed a reduction in both sudden death and deaths from worsening HF. The mechanism by which SV may affect the incidence of ventricular arrhythmias is currently under debate, and the literature provides conflicting results. The aim of our study was to evaluate the potential antiarrhythmic effect of this drug in patients with HFrEF carrying an implantable cardiac defibrillator (ICD) or a cardiac resynchronization therapy with a defibrillator (CRT-D). MethodsThis was a single-center, observational and retrospective study. Inclusion criteria were implantation of an ICD or CRT-D device between 2009 and 2019, age ≥18 years, left ventricle ejection fraction (LVEF) ≤40%, New York Heart Association (NYHA) functional class ≥II, and treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker for at least 12 months, followed by replacement with SV. Exclusion criteria were NYHA class IV, frequent alterations in chronic medication for HFrEF, and implantation of an ICD or CRT-D after the introduction of SV. The primary outcome was the occurrence of ventricular arrhythmias in the form of appropriate device shocks, ventricular fibrillation, or ventricular tachycardia. The comparisons were performed between two periods of time (12 months before and 12 months after SV) in the same group of patients. ResultsFifty-four patients met the inclusion criteria. The mean age was 69.5 ± 1.65 years, and 74.1% of patients were male. The number of patients experiencing appropriate shocks was significantly lower after SV initiation (2% vs. 18%; p=0.016). The percentage of VT (13 vs. 20%; p=0.549) and VF episodes (4% vs. 13% for VF; p=0.289) were also lower, but these differences were not statistically significant. There were no significant differences in the value of NT-proBNP (1128 vs. 775 pg/mL; p=0.858), LVEF (28.4 vs. 29.6%; p=0.315), and left ventricular end-diastolic diameter (65.0 vs. 66.0 mm; p=0.5492). ConclusionSV seems to reduce the risk of arrhythmic events requiring appropriate shock therapy.

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“…In the PARAMOUNT study, sacubitril/valsartan therapy resulted in greater reduction in NT-proBNP at 12 weeks and greater reduction in left atrial size after 36 weeks compared with valsartan ( 16 ). In the PARADIGM-HF study, the further reduction of cardiovascular mortality, including SCD, observed in HFrEF received sacubitril/valsartan is likely due to a combined protective effect against death from HF and fatal ventricular arrhythmias ( 6 , 23 , 24 ). A retrospective study demonstrated sacubitril/valsartan therapy was associated with improvements in echocardiographic parameters, including LVEF, pulmonary atrial pressure and cardiac valvular insufficiency, in patients with HFrEF ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of sacubitril/valsartan on the occurrence of cardiac arrhythmias and the risk of sudden cardiac death in heart failure: A meta-analysis of randomized controlled trials

et al. 2022

Front. Cardiovasc. Med.

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BackgroundSacubitril/valsartan therapy reduced the risks of death and of hospitalization for heart failure (HF). HF and cardiac arrhythmias have shared physiological mechanisems. Therefore, sacubitril/valsartan may exhibit anti-arrhythmic properties in HF. The purpose of this study was to evaluate the effect of sacubitril/valsartan on the occurrence of cardiac arrhythmias and the risk of sudden cardiac death (SCD) in HF.MethodsThis meta-analysis was performed according to PRISMA guidelines. We searched PubMed and Embase (from inception up to 6 February 2022) to identify randomized control trials (RCTs) on the effect of sacubitril/valsartan on the occurrence of cardiac arrhythmias and the risk of SCD in HF. Primary outcomes were the occurrence of atrial arrhythmias, ventricular arrhythmias, and SCD. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model for meta-analysis.ResultsWe included 9 RCTs (published between 2012 and 2021) with 18,500 patients (9,244 sacubitril/valsartan vs. 9,256 active control). Enalapril and valsartan were used as active control in six and two studies, respectively. Follow-up ranged from 2 to 35 months. The cumulative occurrence of events was 76, 13, and 48 per 1,000 patient-years for atrial arrhythmias, ventricular arrhythmias and SCD, respectively. There was no significant association between sacubitril/valsartan therapy and the occurrence of atrial arrhythmias (RR 1.06; 95% CI: 0.97–1.17; P = 0.19) and ventricular arrhythmias (RR 0.86; 95% CI 0.68–1.10; P = 0.24). However, sacubitril/valsartan therapy significantly reduced the risk of SCD (RR 0.79; 95% CI 0.70–0.90; P = 0.03) compared with control.ConclusionNo association between sacubitril/valsartan therapy and the occurrence of atrial and ventricular arrhythmias was found, but sacubitril/valsartan therapy significantly reduced the risk of SCD.

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Ventricular arrhythmias and ARNI: is it time to reappraise their management in the light of new evidence?

Cited by 11 publications

References 62 publications

Sacubitril/valsartan reduces indications for arrhythmic primary prevention in heart failure with reduced ejection fraction: insights from DISCOVER-ARNI, a multicenter Italian register

Sacubitril/valsartan reduces indications for arrhythmic primary prevention in heart failure with reduced ejection fraction: insights from DISCOVER-ARNI, a multicenter Italian register

The Effect of Sacubitril-Valsartan on Ventricular Arrhythmia Burden in Patients With Heart Failure With Reduced Ejection Fraction

Effect of sacubitril/valsartan on the occurrence of cardiac arrhythmias and the risk of sudden cardiac death in heart failure: A meta-analysis of randomized controlled trials

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