Determinants of maximal dose titration of sacubitril/valsartan in clinical practice.

BACKGROUND: Little information is available about the tolerability of uptitration to the maximal dose of sacubitril/valsartan and the predictors and clinical correlates of achieving such a dose. METHODS: All consecutive heart failure patients with reduced ejection fraction (HFrEF) who received sacubitril/valsartan for a class-IB indication in a tertiary heart failure clinic were retrospectively analysed. Predictors of maximal uptitration including associated changes in clinical parameters were assessed in patients with at least 1 follow-up. RESULTS: A total of 401 HFrEF-patients received sacubitril/valsartan. Uptitration was possible in 41% and up to 32% of patients tolerated the maximal dose of sacubitril/valsartan. Younger age (HR = 0.862; CI = 0.751-0.989), higher systolic-blood-pressure (HR = 1.077; CI = 1.014-1.137), lower serum creatinine (HR = 0.064; CI = 0.005-0.822), and higher previous dose of renin-angiotensin-system-inhibitors (RASi [HR = 1.065; CI = 1.016-1.115]) independently predicted a higher odds of tolerating a maximal dose of sacubitril/valsartan. Patients who were seen more frequently in a structured heart failure clinic were also more likely to receive a maximal dose (p = .038). Patient assigned to the maximal dose, were more often able to reduce their loop diuretic dose (p = .001) and more often had an increase in serum creatinine (p = .011), without a higher risk for hyperkalemia (p = .524). An improvement in New York Heart Association class and the rate of heart failure hospitalisations was observed in all patients, independent of the sacubitril/valsartan dose. CONCLUSION: Uptitration to the maximal dose of sacubitril/valsartan is possible in up to 32% of real-world HFrEF-patients in our cohort, which relates to both patient characteristics' as well as heart failure care-related factors.

The Effect of Decongestion on Intrarenal Venous Flow Patterns in Patients With Acute Heart Failure.

BACKGROUND: Discontinuous intrarenal venous flow patterns, as assessed by renal Doppler ultrasound examination, are associated with changes in hemodynamics such as volume expansion and poorer diuretic response in patients with heart failure (HF). We aimed to study intrarenal venous and arterial flow patterns after decongestive treatment in patients with acute HF. METHODS AND RESULTS: Fifteen patients with acute HF were enrolled. Intrarenal venous and arterial flow patterns were assessed at baseline, 1 hour after administration of loop diuretics, at day 2 and day 3. Among patients hospitalized for acute HF, 13 (87%) had a discontinuous venous flow pattern at admission. After decongestive treatment, a significant improvement of the venous impedance index (P = .021) and venous discontinuity index (P = .004) was observed at day 3 compared with baseline. There was no effect on the intrarenal arterial flow patterns. CONCLUSIONS: In patients who exhibit discontinuous renal venous flow patterns hospitalized for decongestive treatment owing to acute HF led to a normalization of intrarenal venous flow to a continuous pattern.

Rationale and design of the IRON-CRT trial: effect of intravenous ferric carboxymaltose on reverse remodelling following cardiac resynchronization therapy.

AIMS: Iron deficiency is common in heart failure with reduced ejection fraction (HFrEF). In patients with cardiac resynchronization therapy (CRT), it is associated with a diminished reverse remodelling response and poor functional improvement. The latter is partially related to a loss in contractile force at higher heart rates (negative force-frequency relationship). METHODS AND RESULTS: The effect of intravenous ferric carboxymaltose on reverse remodelling following cardiac resynchronization therapy (IRON-CRT) trial is a multicentre, prospective, randomized, double-blind controlled trial in HFrEF patients who experienced incomplete reverse remodelling (defined as a left ventricular ejection fraction below <45%) at least 6 months after CRT. Additionally, patients need to have iron deficiency defined as a ferritin below 100 µg/L irrespective of transferrin saturation or a ferritin between 100 and 300 µg/L with a transferrin saturation <20%. Patients will be randomized to either intravenous ferric carboxymaltose (dose based according to Summary of Product Characteristics) or intravenous placebo. The primary objective is to evaluate the effect of ferric carboxymaltose on metrics of cardiac reverse remodelling and contractility, measured by the primary endpoint, change in left ventricular ejection fraction assessed by three-dimensional (3D) echo from baseline to 3 month follow-up and the secondary endpoints change in left ventricular end-systolic and end-diastolic volume. The secondary objective is to determine if ferric carboxymaltose is capable of improving cardiac contractility in vivo, by assessing the force-frequency relationship through incremental biventricular pacing. A total of 100 patients will be randomized in a 1:1 fashion. CONCLUSIONS: The IRON-CRT trial will determine the effect of ferric carboxymaltose on cardiac reverse remodelling and rate-dependent cardiac contractility in HFrEF patients.