Short-term effects of sacubitril/valsartan therapy on myocardial oxygen consumption and energetic efficiency of cardiac work in heart failure with reduced ejection fraction: A randomized controlled study.

AIMS: We sought to evaluate the mechanism of angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan therapy and compare it with a valsartan-only control group in patients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: The study was a phase IV, prospective, randomized, double-blind, parallel-group study in patients with New York Heart Association class II-III heart failure and left ventricular ejection fraction (LVEF) ≤35%. During a 6-week run-in period, all patients received valsartan therapy, which was up-titrated to the highest tolerated dose level (80 mg bid or 160 mg bid) and then randomized to either valsartan or sacubitril/valsartan. Myocardial oxygen consumption, energetic efficiency of cardiac work, cardiac and systemic haemodynamics were quantified using echocardiography and 11 C-acetate positron emission tomography before and after 6 weeks of therapy (on stable dose) in 55 patients (ARNI group: n = 27, mean age 63 ± 10 years, LVEF 29.2 ± 10.4%; and valsartan-only control group: n = 28, mean age 64 ± 8 years, LVEF 29.0 ± 7.3%; all p = NS). The energetic efficiency of cardiac work remained unchanged in both treatment arms. However, both diastolic (-4.5 mmHg; p = 0.026) and systolic blood pressure (-9.8 mmHg; p = 0.0007), myocardial perfusion (-0.054 ml/g/min; p = 0.045), and left ventricular mechanical work (-296; p = 0.038) decreased significantly in the ARNI group compared to the control group. Although myocardial oxygen consumption decreased in the ARNI group (-5.4%) compared with the run-in period and remained unchanged in the control group (+0.5%), the between-treatment group difference was not significant (p = 0.088). CONCLUSIONS: We found no differences in the energetic efficiency of cardiac work between ARNI and valsartan-only groups in HFrEF patients. However, ARNI appears to have haemodynamic and cardiac mechanical effects over valsartan in heart failure patients.

Multipronged intervention strategy to control an outbreak of Clostridium difficile infection (CDI) and its impact on the rates of CDI from 2002 to 2007.

OBJECTIVE: At the end of 2002, a new, more virulent strain of Clostridium difficile, designated BI/NAP1, was the cause of a massive outbreak of infection in the province of Quebec. This particular strain was associated with a dramatic increase in morbidity and mortality among affected patients in 2003-2004. We tested and implemented a multipronged infection control approach to curtail the rate of C. difficile infection (CDI). DESIGN: Five-year observational study. SETTING: A 554-bed, acute care tertiary hospital, the largest single medical center in Quebec, Canada. METHODS: To curtail the magnitude of the outbreak, we implemented a global strategy consisting of rapid C. difficile testing for all hospitalized patients who had at least 1 occurrence of liquid stool, the rapid isolation of patients infected with C. difficile in a dedicated ward with a specially trained housekeeping team, a global hand hygiene program, and the hiring of infection control practitioners. Antibiotic consumption at the institutional level was also monitored during the 5-year surveillance period. Cases of hospital-acquired CDI per 1,000 admissions were continuously monitored on a monthly basis during the entire surveillance period. RESULTS: The highest recorded CDI rate was 42 cases per 1,000 admissions in January 2004. Once additional infection control resources were put in place, the rate decreased significantly during the period from April 2005 to March 2007. During the 2003-2004 period, there were 762 cases of CDI (mean annual rate, 37.28 cases per 1,000 admissions) recorded in our study, compared with 292 cases of CDI (14.48 cases per 1,000 admissions) during the 2006-2007 period (OR, 0.379 [95% CI, 0.331-0.435]; p< .001), a 61% reduction. In March 2007, the equivalent of 4 full-time equivalent infection control practitioners were in place, which gave a ratio of 0.96 infection control practitioners per 133 beds in use, compared with the ratio of 0.24 infection control practitioners per 133 beds in use in 2003, and the total number of hours dedicated to cleaning and housekeeping increased by 26.2%. The total amount of antibiotics used in the hospital did not vary significantly from 2002 to 2007, although there were changes in the classes antibiotic used. CONCLUSION: The implementation of a multipronged intervention strategy to control the outbreak of CDI significantly improved the overall situation at the hospital and underlined the importance of investing in stringent infection control practices.