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The therapy or prevention of atrial fibrillation (AF) is defined as upstream therapy when conducted with the use of drugs, e.g., angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor antagonists, statins, and omega-3 fatty acids, not included in the classes of antiarrhythmic drugs recognized by the Vaughan Williams classification. In our review, we illustrate the rational bases of upstream AF therapy, which encompasses drugs having the property to reduce hemodynamic congestion and cardiac overload, as in the case of ACEIs or angiotensin receptor blockers, as well as drugs able to prevent atrial fibrosis or reduce oxidative stress, such as statins or omega-3 fatty acids, respectively. In this review, randomized controlled trials (RCTs) conducted with the abovementioned drugs are examined. Really, these RCTs have generated mixed results. In the context of the prevention and therapy of AF, our experience is then presented, relating to a patient with heart failure and reduced left ventricular ejection fraction, with a history of relapsing episodes of paroxysmal AF. In this patient, administration of sacubitril/valsartan at appropriate doses allowed recovery of the sinus rhythm. Therefore this case testifies how the upstream therapy of AF might have good results when conducted with sacubitril/valsartan. Thus, RCTs with adequate statistical power are warranted in order to confirm the preliminary encouraging result of our case report, and validate a useful role of sacubitril/valsartan as an upstream therapy of AF., Competing Interests: The authors Renato De Vecchis, Andrea Paccone and Marco Di Maio have no conflicts of interest that are directly relevant to the content of this study., (Copyright 2020, De Vecchis et al.)

Background: The peak atrial longitudinal strain (PALS) is primarily an index of the reservoir function of atrial chambers. The conceptual basis exists to hypothesize that sacubitril/valsartan improves the expandability of atrial chambers in the reservoir phase of the atrial mechanical cycle, as a consequence of its effect of prolonging the half-life of natriuretic peptides. Therefore in this retrospective study we evaluated the repercussions of the administration of sacubitril/valsartan maintained for at least 12 months on the PALS., Methods: In our retrospective study a cohort of 40 patients treated with sacubitril/valsartan has been compared with a second cohort subjected to the conventional treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker. A general criterion to be satisfied was the presence of at least one episode of atrial fibrillation (AF) in the history of the enrolled patients. The study population was composed of New York Heart Association (NYHA) class II/III chronic heart failure (CHF) patients, due to the fact that the treating physicians of the patients whose clinical records were used as source of data, complied with the international guidelines that have so far validated sacubitril/valsartan exclusively for the CHF therapy. The aims were to verify whether the 1-year administration of sacubitril/valsartan is effective in improving the PALS, and also ascertain whether the drug is associated with a decreased risk of AF relapses over a mean retrospective observation period of 12 months., Results: Sacubitril/valsartan cohort was proven to benefit from a significant increase in average values of PALS (median: 26.5%; interquartile range (IQR): 22% - 30%), opposed to the much less pronounced increase in PALS found in the conventional therapy cohort (median: 22.5%; IQR: 18% - 25.5%). Additionally, the comparison made by means of one-way analysis of variance regarding the mean changes of PALS values, outlined clearly that the sacubitril/valsartan users had an increase in PALS after 1 year of therapy significantly greater (P < 0.001) compared to the patients taking the conventional drugs. Moreover, a risk significantly higher of AF recurrences (P = 0.001) was identified in the conventional therapy group compared to the sacubitril/valsartan group during a 12-month retrospective observation period., Conclusions: In the present retrospective cohort study a higher increase of PALS has been shown in the cohort treated with sacubitril/valsartan. Moreover, a reduced risk of AF recurrences has been shown in the sacubitril/valsartan users compared to the patients with CHF subjected to conventional treatment., Competing Interests: The authors Renato De Vecchis, Andrea Paccone and Marco Di Maio do not have any conflict of interest to declare concerning the present article., (Copyright 2020, De Vecchis et al.)

Background: Clinical efficacy of sacubitril/valsartan administered for the recommended indication of chronic heart failure (CHF) patients with New York Heart Association (NYHA) classes II-III appears to be higher than one would expect based on the drug-induced variations of the left ventricular ejection fraction (LVEF). More thorough investigations with the use of indicators of longitudinal systolic function have been therefore recommended to verify whether a part of the clinical improvement achieved with the use of sacubitril/valsartan could be supported by a reverse remodeling ensuing from changes other than a simple LVEF increase., Methods: In the present retrospective cohort study, which collected the pertinent data from two centers devoted to clinical management of outpatients with CHF and dating back to the years 2017 and 2018, we separated patients treated with sacubitril/valsartan from those treated with conventional medical therapy, including angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). For the rest, the therapies practiced in the two groups, patients under sacubitril/valsartan and controls, were almost identical, including similar doses of beta-blockers and mineralocorticoid receptor antagonists (MRAs) in the two cohorts, plus loop diuretics, with the latter administered at variable doses. The endpoints were the variations of LVEF and global left ventricular longitudinal strain (GLS) over a study period not shorter than 1 year., Results: One hundred thirty-two patients were collected within our retrospective cohort study, of whom 44 were treated with sacubitril/valsartan and 88 were subjected to conventional therapy. All patients were marked by heart failure with reduced (LVEF ≤ 40%) left ventricular ejection fraction (HFREF). The mean duration of the retrospective observation period was 14 ± 3 months. In controls, LVEF was improved after a year of therapy from 38.071 ± 5.445% (mean ± standard deviation) to 41.595 ± 5.282%. On the contrary, no significant improvement in the controls could be identified for the GLS, from -12.059 ± 4.016% to -12.250 ± 4.287%. In analogy with controls, patients assigned to sacubitril/valsartan showed a significant increase in LVEF after 1 year of treatment from 39.714 ± 4.789% to 42.119 ± 5.683% (P < 0.001). However, differently from the controls, sacubitril/valsartan group exhibited a significant improvement in GLS from -10.142 ± 3.080% to -18.238 ± 7.284% (P < 0.001)., Conclusions: The present retrospective cohort study demonstrated that the use of sacubitril/valsartan for HFREF patients, extended for a mean duration of 14 months, yields a significant improvement in the echocardiographic parameters of systolic function along the transverse (LVEF) and longitudinal (GLS) axis. For the GLS in particular, a clear superiority emerges in comparison with conventional therapy including ACE inhibitor or ARBs. From these data, the hypothesis could be derived of a possible useful role of sacubitril/valsartan also for the therapy of HFpEF. In this regard, more exhaustive clarifications ensuing from the ongoing randomized controlled trials (RCTs) are eagerly awaited., Competing Interests: The authors Renato De Vecchis, Andrea Paccone and Marco Di Maio do not have any conflict of interest to declare concerning the present article., (Copyright 2019, De Vecchis et al.)

Competing Interests: The authors Renato De Vecchis, Andrea Paccone and Carmelina Ariano do not have any conflicts of interest to declare concerning the present article.

Background: Secondary prevention of atrial fibrillation (AF) could be carried out by means of antiarrhythmic drugs; however this strategy has not received any endorsement because these drugs are burdened by a high risk of proarrhythmic events (flecainide, sotalol) or extracardiac effects (amiodarone)., Methods: In our retrospective cohort study we have compared amiodarone 200 mg per day with the strategy implying the renunciation of any specific drug as well as with the approach using oral anticoagulant (rivaroxaban) or a combined approach including amiodarone plus rivaroxaban., Results: A total of 255 patients with a history of AF (paroxysmal, persistent or long-lasting persistent) successfully treated with achievement of sinus rhythm have been gathered. Amiodarone has been the most effective option for AF secondary prevention, with regard to the recurrences of AF as well as rehospitalizations: P (Kruskal-Wallis test) < 0.05 for both, over a median follow-up of 24 months., Conclusions: Patients kept free from any specific drug therapy have been shown to experience more numerous AF relapses and related rehospitalizations. On the contrary, the amiodarone use has been associated with a decreased risk of AF recurrences and hospital admissions. Thus, amiodarone might be an efficacious tool for realizing a successful long-term AF secondary prevention., Competing Interests: The authors Renato De Vecchis, Andrea Paccone and Marco Di Maio do not have any conflicts of interest to declare concerning the present article.

Competing Interests: All authors do not have any conflict of interest to declare concerning the present article.