Safety and Effectiveness of Drug up Titration by Nurses Specialized in Heart Failure (HF) Patients

Number of participants with worsening renal function during the titration process (from baseline to 4 month) that could be associated to the titration process (Creatinine increase >50% baseline creatinine or creatinine>3mg/dl, or Estimated Glomerular Filtration<25 ml/min/1.73 m2)

Number of participants with Potassium≥ 5.5 meq/l during the titration process (from baseline to 4 month) that could be associated to this titration process

Description: Number of participants with symptomatic hypotension during the titration process (from baseline to 4 month) that could be associated to this titration process. Symptomatic hypotension defined as symptoms such as dizziness or light headedness, associated to hypotension

Number of participants with Heart Rate (HR) < 50 beats per minute during the titration process (from baseline to 4 month) , which could be associated to the titration process. (with or without symptoms)

Number of patients with AV Block during the titration process, associated to the BB titration

Number of patients with worsening of heart failure signs and symptoms during the titration process ( from baseline to 4 month) which could be associated to the titration process.

Number of patients with admissions due to titration ( not due to other causes)

Number of patients: Mortality due to titration ( not due to other causes)

number of paticipants with drug Stop ( withdrawal) that occur during the titration process that could be due to an adverse event. ( it can be not only due to an adverse event but because there is no need of this drug or its substitution for another kind of drug)

Change in % Left Ventricular Ejection Fraction (difference of change from baseline to 6 months between groups) Ejection fraction is a measurement of the percentage of blood leaving the heart each time it contracts.

Nt-proBNP (N-terminal pro-B type natriuretic peptide) Improvement (Decrease) difference of change from baseline to 6 months between groups, mean (SD)

6 minute walking test improvement ( change) meters.Improvement (difference of change from baseline to 6 months between groups Six minute walking test. Measurement of exercise capacity is an integral element in assessment of patients with cardiopulmonary disease. It provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions. The six-minute walk test (6MWT) measures the distance (meters) an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is allowed to self-pace and rest as needed as they traverse back and forth along a marked walkway.

Number of participants class I-IV New York Heart Association (NYHA) functional classification, based on severity of symptoms and physical activity:

NYHA I (better): No limitation of physical activity; NYHA II: Slight limitation of ordinary physical activity, breathlessness; NYHA III: marked limitation of physical activity. Comfortable at rest, but less than ordinary activity results in undue breathlessness, fatigue or palpitations; NYHA IV ( worse): unable to carry on any physical activity without discomfort.Symptoms at rest can be present. If any physical activity is undertaken discomfort is increased.

Quality of Life, measured by Minnesota Living with Heart Failure Questionnaire. Improvement (change) from baseline to 6 months.

Minnesota Living With Heart Failure Questionnaire (MLWHFQ). The content of this questionnaire was selected to be representative of the ways heart failure and treatments can affect the key physical, emotional, social and mental dimensions of quality of life of patients with heart failure. It consist of 21-items with score 0-5. Final evaluation moves from 0 (none) to 105 (very much); a lower score means better quality of life.

European Quality of Life Scale: EuroQol- 5 Dimension index (Range: 1 full health-0 death). It measures health status self-reported by the patient. It has 5 domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension is divided into three levels: 1 no problem; 2 some or moderate problems; 3 extreme problems. The EuroQol Research Foundation converts this information into a single summary index, by applying a formula that attaches specific country values (called weights) to each of the levels in each dimension. The index is calculated by subtracting the mentioned weights from 1, the value for full health.

We measured the EuroQol-5D index improvement (change) from baseline to 6 months.

More information in: EQ-5D-3L-User-Guide_version-6.0 (1).pdf

Number of patients with hospital admissions due to Heart Failure. From Baseline to 6 months

Number of Patients with deaths due to Cardiovascular and non cardiovascular causes

ACEI mean Relative dose is the mean dose of ACEI achieved 4 months after starting titration, relative to target dose (%) described in European guidelines

ARB, angiotensin II receptor blockers, mean relative dose ( % to target dose). Target dose is described in European guidelines.

Measured at 4 months after starting titration.

MRA % relative dose (mean) is the mean dose achieved 4 months after starting titration with regard to target dose (%) described in european guidelines