Ambulatory respiratory rate trends identify patients at higher risk of worsening heart failure in implantable cardioverter defibrillator and biventricular device recipients: a novel ambulatory parameter to optimize heart failure management.

PURPOSE: Respiratory distress is the primary driver for heart failure (HF) hospitalization. Implantable pacemakers and defibrillators are capable of monitoring respiratory rate (RR) in ambulatory HF patients. We investigated changes in RR prior to HF hospitalizations and its near-term risk stratification power. METHODS: NOTICE-HF was an international multi-center study. Patients were implanted with an implantable cardioverter defibrillator or cardiac resynchronization therapy defibrillator, capable of trending daily maximum, median, and minimum RR (maxRR, medRR, minRR). RR from 120 patients with 9 months of follow-up was analyzed. One-tailed Student's t test was used to compare RR values prior to HF events to baseline defined as 4 weeks prior to the events. A Cox regression model was used to calculate the hazard ratios (HR) for the 30-day HF hospitalization risk based on RR values in the preceding month. RESULTS: Daily maxRR, medRR, and minRR were significantly elevated prior to HF events compared to baseline (ΔmaxRR 1.8 ± 3.0; p = 0.02; ΔmedRR, 2.1 ± 2.8; p = 0.007; ΔminRR, 1.5 ± 2.1, p = 0.008). Risk of experiencing HF events within 30-days was increased if the standard deviation of medRR over the preceding month was above 1.0 br/min (HR = 12.3, 95 % confidence interval (CI) 2.57-59, p = 0.002). The risk remained high after adjusting for clinical variables that differed at enrollment. CONCLUSION: Ambulatory daily respiratory rate trends may be a valuable addition to standard management for HF patients.

The effect of different meal types on the pharmacokinetics of darunavir (TMC114)/ritonavir in HIV-negative healthy volunteers.

This open-label, randomized, crossover study investigated the bioavailability, short-term safety, and tolerability of darunavir (TMC114) coadministered with low-dose ritonavir under fasted conditions and after different meal types in HIV-negative healthy volunteers. All volunteers received ritonavir 100 mg twice daily on days 1 to 5, with a single darunavir 400-mg tablet given on day 3 (darunavir/rtv). Pharmacokinetic parameters for darunavir and ritonavir were determined under fasted conditions and following a standard breakfast, a high-fat breakfast, a nutritional protein-rich drink, or a croissant with coffee. Administration of darunavir/rtv in a fasting state resulted in a decrease in darunavir C(max) and AUC(last) of approximately 30% compared with administration after a standard meal. No significant differences in darunavir plasma concentrations were observed between different fed states. Darunavir/rtv should therefore be administered with food, but exposure to darunavir is not affected by the type of meal.