Venoarterial PCO2 difference: a marker of postoperative cardiac output in children with congenital heart disease

OBJECTIVE: To determine the relationship between venoarterial carbon dioxide gradient (DeltapCO2) and central venous oxygen saturation (ScvO2) in children after cardiac surgery. STUDY DESIGN: A cohort study. PLACE AND DURATION OF STUDY: The Paediatric cardiac intensive care unit of the Aga Khan University Hospital, Karachi, from June 2006 to May 2007. METHODOLOGY: All children admitted in the paediatric cardiac intensive care after complete repair of congenital heart defect using cardiopulmonary bypass were included in the study. Simultaneous arterial and central venous blood gas samples were obtained from a catheter placed in the artery (either radial or femoral) and superior vena cava respectively. Linear regression analysis was performed between ScvO2 and DeltapCO2. RESULTS: Fifty seven children aged from 5 days to 14 years were included and 272-paired simultaneous arterial and central venous samples were analyzed. Mean venous pCO2 was 47.82+/-9.03 mmHg and mean arterial pCO2 was 40.50+/-9.06 mmHg. One hundred seventy four samples had ScvO2 \u3e 70% with mean DeltapCO2 of 5.44+/-2.55 mmHg and 98 samples had ScvO2 \u3c 70% with mean DeltapCO2 of 9.07+/-3.90 mmHg. With ScvO2 \u3c 70%, 77 samples had DeltapCO2 of \u3e 6 mmHg while only 21 samples had DeltapCO2 of \u3c 6 mmHg (p \u3c 0.001). On the contrary with ScvO2 \u3e 70%, 71 samples had DeltapCO2 of \u3e 6 mmHg and 103 samples had DeltapCO2 of \u3c 6 mmHg. Coefficient of correlation (R2) between 0.340 was ScvO2 and DeltapCO2. CONCLUSION: Elevated DeltapCO2 is practical and can be utilized as a useful adjunct to low ScvO2 in the assessment of low cardiac output syndrome in children after cardiac surgery

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)