The aim of this study was to evaluate the effects of Sacubitril/Valsartan (S/V) on clinical, laboratory and echocardiographic parameters and outcomes in a real-world population with heart failure with reduced ejection fraction (HFrEF). This was a prospective observational study enrolling patients with HFrEF undergoing treatment with S/V. The primary outcome was the composite of cardiac death and HF rehospitalization at 12 months follow-up; secondary outcomes were all-cause death, cardiac death and the occurrence of rehospitalization for worsening HF. The clinical outcome was compared with a retrospective cohort of 90 HFrEF patients treated with standard medical therapy. The study included 90 patients (66.1 ± 11.7 years) treated with S/V. The adjusted regression analysis showed a significantly lower risk for the primary outcome (HR:0.31; 95%CI, 0.11-0.83; p = 0.019) and for HF rehospitalization (HR:0.27; 95%CI, 0.08-0.94; p = 0.039) in S/V patients as compared to the control group. A significant improvement in NYHA class, left ventricular ejection fraction, left ventricular end systolic volume and systolic pulmonary arterial pressure was observed up to 6 months. S/V did not affect negatively renal function and was associated with a significantly lower dose of furosemide dose prescribed at 6-and 12-month follow-up. In this study, S/V reduced the risk of HF rehospitalization and cardiac death at 1 year in patients with HFrEF. S/V improved NYHA class, echocardiographic parameters and need of furosemide, and preserved renal function.Despite the improvements in clinical management and medical therapy of heart failure (HF), the outcome of patients with HF and reduced ejection fraction (HFrEF) remains poor 1 . If compared to the other HF entities, this category shows distinct demographic characteristics, comorbidities, response to therapy, and a substantially higher risk of mortality secondary to sudden cardiac death (SCD) and rehospitalization for worsening HF 2 . Many HFrEF patients are still undertreated and several drugs, such as beta-blockers and ACE inhibitors (ACEi), are under-dosed. This issue is also related to the incorrect risk evaluation by clinicians, who are likely to consider the absence or paucity of symptoms as an indicator of HF stability 3 . In fact, HFrEF is a progressive disorder that, despite the improvement of patient's clinical status achieved with conventional medications, may be associated with a high risk of adverse events at short and long-term follow-up 4 .Current European guidelines 5 recommend the use Sacubitril/Valsartan (S/V), an angiotensin receptorneprilysin inhibitor (ARNI), in replacement of the renin-angiotensin-aldosterone system (RAAS) inhibition in ambulatory HFrEF patients still symptomatic despite optimal medical therapy (OMT). This recommendation comes from a single randomized study named PARADIGM-HF trial 6 , which showed the superiority of S/V compared to Enalapril in reducing the incidence of cardiovascular death or hospitalizations for HF. Few studies have so far investigat...
Heart Failure (HF) is a syndrome, which implies the existence of different phenotypes. The new categorization includes patients with preserved ejection fraction (HFpEF), mid-range EF (HFmrEF), and reduced EF (HFrEF) but the molecular mechanisms involved in these HF phenotypes have not yet been exhaustively investigated. Sirt1 plays a crucial role in biological processes strongly related to HF. This study aimed to evaluate whether Sirt1 activity was correlated with EF and other parameters in HFpEF, HFmrEF, and HFrEF. Seventy patients, HFpEF (n = 23), HFmrEF (n = 23) and HFrEF (n = 24), were enrolled at the Cardiology Unit of the University Hospital of Salerno. Sirt1 activity was measured in peripheral blood mononuclear cells (PBMCs). Angiotensin-Converting Enzyme 2 (ACE2) activity, Tumor Necrosis Factor-alpha (TNF-α) and Brain Natriuretic Peptide (BNP) levels were quantified in plasma. HFpEF showed lower Sirt1 and ACE2 activities than both HFmrEF and HFrEF (p < 0.0001), without difference compared to No HF controls. In HFmrEF and HFrEF a very strong correlation was found between Sirt1 activity and EF (r2 = 0.899 and r2 = 0.909, respectively), and between ACE2 activity and Sirt1 (r2 = 0.801 and r2 = 0.802, respectively). HFrEF showed the highest TNF-α levels without reaching statistical significance. Significant differences in BNP were found among the groups, with the highest levels in the HFrEF. Determining Sirt1 activity in PBMCs is useful to distinguish the HF patients’ phenotypes from each other, especially HFmrEF/HFrEF from HFpEF.
Funding Acknowledgements
Type of funding sources: None.
Aims
Patients with atrial fibrillation (AF) frequently experience sleep disorder breathing, and both conditions are highly prevalent in presence of heart failure (HF). We explored the association between sleep apnea (SA) and the HF status and the incidence of AF in patients with implantable defibrillators (ICD).
Methods
Data were prospectively collected from 411 consecutive HF patients with ICD. The HF status was measured by the multisensor HeartLogic Index, and the ICD-measured Respiratory Disturbance Index (RDI) was computed to identify severe SA. The endpoints were: daily AF burden of ≥5minutes, ≥6hours and ≥23hours.
Results
During a median follow-up of 26 months, the time IN-alert HF state was 13% of the total observation period, according to the HeartLogic algorithm (Index >16). The RDI value was ≥30 episodes/h (severe SA) during 58% of the observation period. An AF burden of ≥5 minutes/day was documented in 139 (34%) patients, ≥6 hours/day in 89 (22%) patients, and ≥23 hours/day in 68 (17%) patients. The IN-alert HF state was independently associated with AF regardless of the daily burden threshold: hazard ratios from 2.17 for ≥5 min/day to 3.43 for ≥23 h/day (p<0.01). The occurrence of severe SA was associated only with AF burden ≥5 min/day (hazard ratio 1.55 [95%CI:1.11-2.16], p=0.001). The combination of HF alert and severe SA accounted for only 6% of the follow-up period and was associated with high rates of AF occurrence (from 28 events/100 patient-years for AF burden≥5 min/day to 22 events/100 patient-years for AF burden≥23 h/day).
Conclusions
In patients with heart failure (HF) and implantable defibrillators (ICD), the occurrence of atrial fibrillation (AF) was independently associated with the worsened HF status measured by a multisensor ICD algorithm and with ICD-diagnosed severe sleep apnea (SA). The HF status was independently associated with AF regardless of the daily burden, while severe SA was mainly associated with shorter AF episodes. The coexistence of these two conditions occurs rarely but is associated with a very high rate of AF occurrence.
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