Scheduled intermittent inotropes for Ambulatory Advanced Heart Failure. The RELEVANT-HF multicentre collaboration.

BACKGROUND: Ambulatory Advanced Heart Failure (AAHF) is characterized by recurrent HF hospitalizations, escalating diuretic requirements, intolerance to neurohormonal antagonists, end-organ dysfunction, short-term reduced life expectancy despite optimal medical management (OMM). The role of intermittent inotropes in AAHF is unclear. The RELEVANT-HF registry was designed to obtain insight on the effectiveness and safety of compassionate scheduled repetitive 24-hour levosimendan infusions (LEVO) in AAHF patients. METHODS: 185 AAHF NYHA class III-IV patients, with ≥2 HF hospitalizations/emergency visits in the previous 6 months and systolic dysfunction, were treated with LEVO at tailored doses (0.05-0.2 µg/kg/min) without prior bolus every 3-4 weeks. We compared data on HF hospitalizations (percent days spent in hospital, DIH) in the 6 months before and after treatment start. RESULTS: Infusion-related adverse events occurred in 23 (12.4%) patients the commonest being ventricular arrhythmias (16, 8.6%). During follow-up, 37 patients (20%) required for clinical instability treatment adjustments (decreases in infusion dose, rate of infusion or interval). From the 6 months before to the 6 months after treatment start we found lower DIH (9.4 (8.2) % vs 2.8 (6.6) %, p < 0.0001), cumulative number (1.3 (0.6) vs 1.8 (0.8), p = 0.0001) and length of HF admissions (17.4 (15.6) vs 21.6 (13.4) days, p = 0.0001). One-year survival was 86% overall and 78% free from death/LVAD/urgent transplant. CONCLUSIONS: In AAHF patients, who remain symptomatic despite OMM, LEVO is well tolerated and associated with lower overall length of hospital stay during six months. This multicentre clinical experience underscores the need for a randomized controlled trial of LEVO impact on outcomes in AAHF patients.

[Tolerability and efficacy of aldosterone inhibition with canrenone in heart failure: the real-world experience of an outpatient heart failure clinic]. / Tollerabilità ed efficacia dell'inibizione aldosteronica con canrenone nello scompenso cardiaco: l'esperienza nel mondo reale di un ambulatorio dedicato.

BACKGROUND: The aim of this study was to evaluate retrospectively the tolerability, safety and efficacy of antialdosterone therapy in patients with heart failure admitted to our ambulatory from June 1995 to September 2003. METHODS: One hundred and fifty-seven consecutive patients (mean age 64 +/- 11.6 years) were enrolled in the study; they were in NYHA class I-IV, on ACE-inhibitor or angiotensin receptor blocker therapy, and were treated with canrenone if they were in NYHA class I-IV having experienced a previous cardiac event and did not show asymptomatic left ventricular dysfunction or creatinine levels at baseline > or = 2.5 mg/dl, hyperkalemia > or = 5.2 mEq/l, and poor compliance. The mean follow-up was 38.7 +/- 21.2 months. Patients were divided into two groups according to either therapy (group 1: 124 patients, 79%, on antialdosterone therapy; group 2: 33 patients, 21%, on no antialdosterone therapy) or ischemic and non-ischemic etiology (group A: 71 patients, 45.2%, and group B: 86 patients, 54.8%, respectively). Serum creatinine and plasma potassium levels, left ventricular ejection fraction, NYHA class, adverse effects, and mortality were evaluated. RESULTS: The mean dose of canrenone was 37 +/- 19.9 mg/day. Creatinine levels did not change significantly whereas potassium levels slightly increased in group 1 vs group 2 (p < 0.01) and in group A vs group B (p < 0.01). Treatment was discontinued by only 12 patients (8.1%) due to hyperkalemia in 8 cases (6.5%), gynecomastia in 2 cases (1.6%), urticaria in 1 case (0.8%), and nausea in 1 case (0.8%). Left ventricular ejection fraction increased in all groups (p < 0.001) with the exception of the subgroup B/group 2 (p = NS). The NYHA class improved significantly in group 1 (p < 0.01). The total mortality rate was 10.8% (17 cases), of which 10.5% (13 cases) in group 1 and 12.1% (4 cases) in group 2 and due to sudden death in 3 group 1 patients (2.4%) and in 2 group 2 patients (6%). CONCLUSIONS: This study shows a good tolerability, safety, and efficacy, and poor adverse effects of canrenone therapy in combination with ACE-inhibitors, angiotensin receptor blockers and beta-blockers in patients with chronic heart failure. Therapy should be monitored by serial clinical and laboratory controls and gradually titrated up to the maximal tolerated dosage.