This study sought to assess, for the first time, the relationship between serum concentrations of the soluble interleukin-1 receptor family member ST2 (sST2) and serial change in left ventricular ...(LV) function after acute myocardial infarction (AMI).
Serum sST2 levels are elevated early after AMI and are associated with lower pre-discharge LV ejection fraction and adverse cardiovascular outcomes.
The sST2 levels were measured in 100 patients (mean age 58.9 +/- 12.0 years; 77% male), admitted with AMI with resultant LV systolic dysfunction, at baseline and at 12 and 24 weeks. Patients underwent cardiac magnetic resonance imaging and measurement of N-terminal pro-brain natriuretic peptide, norepinephrine, and aldosterone at each time point.
Median sST2 decreased from 263.3 pg/ml at baseline to 140.0 pg/ml at 24 weeks (p < 0.001). Serum sST2 correlated significantly with LV ejection fraction at baseline (r = -0.30, p = 0.002) and 24 weeks (r = -0.23, p = 0.026); change in sST2 correlated with change in LV end-diastolic volume index (r = -0.24, p = 0.023). Level of sST2 was positively associated with infarct volume index at baseline (r = 0.26, p = 0.005) and 24 weeks (r = 0.22, p = 0.037), and with change in infarct volume index (r = -0.28, p = 0.001). Level of sST2 was significantly higher in patients with greater infarct transmurality and endocardial extent, and in the presence of microvascular obstruction. Level of sST2 correlated significantly with norepinephrine and aldosterone, but not with N-terminal pro-brain natriuretic peptide.
Measurement of sST2 early after AMI assists in the prediction of medium-term LV functional recovery. Novel relationships were observed between sST2, infarct magnitude/evolution, and aldosterone. Serum sST2 may be of pathophysiological importance in ventricular and infarct remodeling after AMI. (Effects of Eplerenone on Left Ventricular Remodelling Following Heart Attack; NCT00132093).
Abstract
Background and Aims
To examine the decongestive effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin compared to the thiazide-like diuretic metolazone in patients ...hospitalized for heart failure and resistant to treatment with intravenous furosemide.
Methods and results
A multi-centre, open-label, randomized, and active-comparator trial. Patients were randomized to dapagliflozin 10 mg once daily or metolazone 5–10 mg once daily for a 3-day treatment period, with follow-up for primary and secondary endpoints until day 5 (96 h). The primary endpoint was a diuretic effect, assessed by change in weight (kg). Secondary endpoints included a change in pulmonary congestion (lung ultrasound), loop diuretic efficiency (weight change per 40 mg of furosemide), and a volume assessment score. 61 patients were randomized. The mean (±standard deviation) cumulative dose of furosemide at 96 h was 977 (±492) mg in the dapagliflozin group and 704 (±428) mg in patients assigned to metolazone. The mean (±standard deviation) decrease in weight at 96 h was 3.0 (2.5) kg with dapagliflozin compared to 3.6 (2.0) kg with metolazone mean difference 0.65, 95% confidence interval (CI) −0.12,1.41 kg; P = 0.11. Loop diuretic efficiency was less with dapagliflozin than with metolazone mean 0.15 (0.12) vs. 0.25 (0.19); difference −0.08, 95% CI −0.17,0.01 kg; P = 0.10. Changes in pulmonary congestion and volume assessment score were similar between treatments. Decreases in plasma sodium and potassium and increases in urea and creatinine were smaller with dapagliflozin than with metolazone. Serious adverse events were similar between treatments.
Conclusion
In patients with heart failure and loop diuretic resistance, dapagliflozin was not more effective at relieving congestion than metolazone. Patients assigned to dapagliflozin received a larger cumulative dose of furosemide but experienced less biochemical upset than those assigned to metolazone.
Trial registration
ClinicalTrials.gov Identifier: NCT04860011
Structured Graphical Abstract
Structured Graphical Abstract
ADVOR, Acetazolamide in Decompensated Heart Failure with Volume Overload; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; eGFR, estimated glomerular filtration rate; IV, intravenous.
The uptake of sacubitril/valsartan since the PARADIGM study confirmed its beneficial effects on outcomes over enalapril in chronic systolic heart failure has inevitably led to potential interactions ...with co-prescribed medications in real-world patients. We report two cases that raise the possibility of an interaction between sacubitril/valsartan and the class Ib anti-arrhythmic mexiletine resulting in proarrhythmic effects. We discuss the pharmacokinetics of both agents and posit potential mechanistic interactions that suggest caution should be used and careful monitoring for (ventricular) arrhythmias applied in patients receiving sacubitril/valsartan and mexiletine.
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