Effects of Sacubitril/Valsartan in Patients with High Arrhythmic Risk and an ICD: A Longitudinal Study

Casale, Matteo; Correale, Michele; Laterra, Giulia; Vaccaro, Vittoria; Morabito, Claudia; Crea, Pasquale; Signorelli, Salvatore Santo; Katsiki, Niki; Luzza, Francesco; Gregorio, Cesare de; Dattilo, Giuseppe

doi:10.1007/s40261-020-00995-3

Cited by 19 publications

(19 citation statements)

References 34 publications

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“…Despite the proportion of high-dose ARNI recipients in large pivotal trials, the adherence to multidrug therapy remains a challenging item in clinical practice, even if adults with cardiovascular diseases are prone to polypharmacy due to comorbidities and complexity of medication regimens [ 15 , 16 ]. Though we have already observed drug-related benefit in patients at a high risk of arrhythmic disorders, high-dose ARNI therapy has some practical limitations, especially in patients with low BP symptoms [ 17 , 18 ]. In fact, despite suitable clinical characteristics, Martens et al demonstrated that high doses were administered only to 32% of HFrEF patients [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Low- vs high-dose ARNI effects on clinical status, exercise performance and cardiac function in real-life HFrEF patients

Corrado

Dattilo

Coppola

et al. 2021

Eur J Clin Pharmacol

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Purpose Only a few studies are available on dose-related effects of sacubitril/valsartan (angiotensin receptor neprilysin inhibition (ARNI)) in real-life patients with heart failure and reduced ejection fraction (HFrEF). We sought to investigate clinical and functional effects in real-life HFrEF patients receiving ARNI at a different cumulative dose. Methods This was an observational study in consecutive outpatients admitted for HFrEF from October 2017 to June 2019. The PARADIGM criteria were needed for enrolment. ARNI was uptitrated according to blood pressure, drug tolerability, renal function and kaliemia. At least 10-month follow-up was required in each patient. Clinical assessment, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-min walk test and strain echocardiography were performed in each patient on a regular basis during the observational period. At the end of the study, patients were divided into two groups based on the median yearly dose of the ARNI medication. Results A total of 90 patients, 64 ± 11 years, 82% males, were enrolled. The cut-off dose was established in 75 mg BID, and the study population was divided into group A (≤ 75 mg), 52 patients (58%), and group B (> 75 mg), 38 patients (42%). The follow-up duration was 12 months (range 11–13). NYHA class, KCCQ score and 6MWT performance ameliorated in both groups, with a quicker time to benefit in group B. The proportion of patients walking > 350 m increased from 21 to 58% in group A ( p < 0.001), and from 29 to 82% in group B ( p < 0.001). A positive effect was also disclosed in the left ventricular remodelling, strain deformation and diastolic function. Conclusion One-year ARNI treatment was effective in our real-life HFrEF patient population, leading to clinical and functional improvement in both study groups, slightly greater and with a shorter time to benefit in group B. Supplementary information The online version contains supplementary material available at 10.1007/s00228-021-03210-0.

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Section: Discussionmentioning

confidence: 99%

Low- vs high-dose ARNI effects on clinical status, exercise performance and cardiac function in real-life HFrEF patients

Corrado

Dattilo

Coppola

et al. 2021

Eur J Clin Pharmacol

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“…Management of HF is in constant evolution, 21 even by the interplay with novel pharmacologic approaches. 22 We think that in this scenario, optimal results could be reached by the use of an active fixation lead in CS.…”

Section: Discussionmentioning

confidence: 89%

“…The use of LV active fixation lead remained a significant variable both for HF rehospitalization and in death due to HF. Management of HF is in constant evolution, 21 even by the interplay with novel pharmacologic approaches 22 . We think that in this scenario, optimal results could be reached by the use of an active fixation lead in CS.…”

Section: Discussionmentioning

confidence: 99%

Novel active fixation lead guided by electrical delay can improve response to cardiac resynchronization therapy in heart failure

Casale¹,

Mezzetti²,

Fazio

et al. 2021

ESC Heart Failure

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Aims Cardiac resynchronization therapy (CRT) for heart failure (HF) recently has shown optimal results by targeting electrically delayed sites in coronary sinus (CS) branches. However this purpose often cannot be reached because of unstable left ventricular (LV) lead position. In current study were assessed the long‐term effects of the novel active fixation LV lead in CS, guided by electrical delay (QLV), in patients with HF due to coronary artery disease. Methods One hundred eighty‐five consecutive patients underwent CRT with intraoperative evaluation of QLV in the target position of the LV lead. When the novel active fixation LV lead was available, 98 consecutive patients received it, composing the Fix group. They were compared with 87 patients with a conventional passive fixation lead (No Fix group). The final LV lead position was assessed by fluoroscopy. Clinical response to CRT was assessed within a period of about 3 years: patients experiencing HF rehospitalization and death due to HF were defined as non‐responders. Results There were no significant differences between groups in the final position of LV lead in left anterior oblique view (Pearson χ2 = 0.12; P = 0.73). In right anterior oblique view, a basal position was reached more in the Fix group (38%) than in the No Fix group (6.5%) (Pearson χ2 = 23.095; P < 0.001). QLV was significantly greater in the Fix group (122.6 ± 33.2 ms; SE = 3.6) than in the No Fix group (97.5 ± 37.8 ms; SE = 4.9) (t = 4.17; P < 0.001). Rehospitalizations for HF were 37 in the No Fix group and 14 in the Fix group. Deaths due to HF were 49 in the No Fix group and 18 in the Fix group. Survival analysis, assessed by Cox regression, showed that the Fix group had a better outcome both for HF rehospitalizations [hazard ratio (HR) = 0.48; 95% confidence interval (CI) = 0.25–0.9; P = 0.023] and death due to HF (HR = 0.55; 95% CI = 0.31–0.97; P = 0.04) in comparison with the No Fix group. Adjustment for baseline characteristics by multivariate analysis showed that an active fixation lead in CS, as a covariate, was still significant both for HF rehospitalizations (HR 0.46; 95% CI = 0.24–0.88; P = 0.019) and for death due to HF (HR 0.5; 95% CI = 0.28–0.9; P = 0.021). Conclusions The novel active fixation LV lead allowed to target sites with greater QLV. Often maximum QLV was documented in basal segments, were stability of conventional passive fixation leads is not enough. Patients receiving it experienced less HF rehospitalizations and less death due to HF. Active fixation lead in CS guided by QLV can improve long‐term prognosis in patients with HF due to coronary artery disease undergoing to CRT.

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“…Interestingly, mild angioedema was documented in some patients receiving sacubitril/valsartan, although the number was not statistically different from the incidence in enalapril group [16]. These beneficial effects were observed across LV ejection fraction (LVEF) spectrums [17], occurred within 6 months of therapy initiation [18] and persisted even after 18 months [19]. By contrast, initial improvements in daytime physical activity and 6-min walking test with sacubitril/valsartan in HFrEF patients were no longer significant after 12 weeks in the OUTSTEP-HF study [20].…”

Section: Heart Failurementioning

confidence: 98%

Angiotensin Receptor-Neprilysin Inhibitor (ARNI) and Cardiac Arrhythmias

Sutanto

Dobrev

Heijman

2021

IJMS

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The renin-angiotensin-aldosterone system (RAAS) plays a major role in cardiovascular health and disease. Short-term RAAS activation controls water and salt retention and causes vasoconstriction, which are beneficial for maintaining cardiac output in low blood pressure and early stage heart failure. However, prolonged RAAS activation is detrimental, leading to structural remodeling and cardiac dysfunction. Natriuretic peptides (NPs) are activated to counterbalance the effect of RAAS and sympathetic nervous system by facilitating water and salt excretion and causing vasodilation. Neprilysin is a major NP-degrading enzyme that degrades multiple vaso-modulatory substances. Although the inhibition of neprilysin alone is not sufficient to counterbalance RAAS activation in cardiovascular diseases (e.g., hypertension and heart failure), a combination of angiotensin receptor blocker and neprilysin inhibitor (ARNI) was highly effective in several clinical trials and may modulate the risk of atrial and ventricular arrhythmias. This review summarizes the possible link between ARNI and cardiac arrhythmias and discusses potential underlying mechanisms, providing novel insights about the therapeutic role and safety profile of ARNI in the cardiovascular system.

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Effects of Sacubitril/Valsartan in Patients with High Arrhythmic Risk and an ICD: A Longitudinal Study

Cited by 19 publications

References 34 publications

Low- vs high-dose ARNI effects on clinical status, exercise performance and cardiac function in real-life HFrEF patients

Low- vs high-dose ARNI effects on clinical status, exercise performance and cardiac function in real-life HFrEF patients

Novel active fixation lead guided by electrical delay can improve response to cardiac resynchronization therapy in heart failure

Angiotensin Receptor-Neprilysin Inhibitor (ARNI) and Cardiac Arrhythmias

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