Rationale and Design of the DECONGEST (Diuretic Treatment in Acute Heart Failure with Volume Overload Guided by Serial Spot Urine Sodium Assessment) Study.

AIMS: To evaluate whether early combination diuretic therapy guided by serial post-diuretic urine sodium concentration (UNa+) assessments in acute heart failure (AHF) facilitates safe and effective decongestion. METHODS: The Diuretic Treatment in Acute Heart Failure with Volume Overload Guided by Serial Spot Urine Sodium Assessment (DECONGEST) study is a pragmatic, 2-centre, randomized, parallel-arm, open-label study, aiming to enrol 104 patients with AHF and clinically evident fluid overload, requiring treatment with intravenous loop diuretics. Patients are randomized to receive standard of care or a bundled approach comprising: (1) systematic post-diuretic UNa+ assessments until successful decongestion, defined as no remaining clinical signs of fluid overload with a post-diuretic UNa+ ≤80 mmol/L; (2) thrice-daily intravenous loop diuretic bolus therapy, with dosing according to estimated glomerular filtration rate; (3) upfront use of intravenous acetazolamide (500 mg OD); and (4) full nephron blockade with high-dose oral chlorthalidone (100 mg OD) and intravenous canreonate (200 mg OD) for diuretic resistance, defined as persisting signs of fluid overload with a post-diuretic UNa+ ≤80 mmol/L. The primary endpoint of the DECONGEST study is a hierarchical composite of (1) survival at 30 days; (2) days alive and out of hospital or care facility up to 30 days; and (3) greater relative decrease in natriuretic peptide levels from baseline to day 30. CONCLUSION: The DECONGEST study aims to determine whether an intensive diuretic regimen focused on early combination therapy, guided by serial post-diuretic UNa+ assessments, safely enhances decongestion, warranting further evaluation in a larger trial powered for clinical events.

Clinical Significance of Exercise Pulmonary Hypertension With a Negative Diastolic Stress Test for Suspected Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Half of patients with heart failure with preserved ejection fraction (HFpEF) remain undiagnosed by resting evaluation alone. Therefore, exercise testing is proposed. The diastolic stress test (DST), however, has limited sensitivity. We aimed to determine the clinical significance of adding the mean pulmonary artery pressure over cardiac output (mPAP/CO) slope to the DST in suspected HFpEF. METHODS AND RESULTS: In this prospective cohort study, consecutive patients (n=1936) with suspected HFpEF underwent exercise echocardiography with simultaneous respiratory gas analysis. These patients were stratified by exercise E over e' (exE/e') and mPAP/CO slope, and peak oxygen uptake, natriuretic peptides (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and score-based HFpEF likelihood were compared. Twenty-two percent of patients (n=428) had exE/e'<15 despite a mPAP/CO slope>3 mm Hg/L per min, 24% (n=464) had a positive DST (exE/e'≥15), and 54% (n=1044) had a normal DST and slope. Percentage of predicted oxygen uptake was similar in the group with exE/e'<15 but high mPAP/CO slope and the positive DST group (-2% [-5% to +1%]), yet worse than in those with normal DST and slope (-12% [-14% to -9%]). Patients with exE/e'<15 but a high slope had NT-proBNP levels and H2FPEF (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder; filling pressure) scores intermediate to the positive DST group and the group with both a normal DST and slope. CONCLUSIONS: Twenty-two percent of patients with suspected HFpEF presented with a mPAP/CO slope>3 mm Hg/L per min despite a negative DST. These patients had HFpEF characteristics and a peak oxygen uptake as low as patients with a positive DST. Therefore, an elevated mPAP/CO slope might indicate HFpEF irrespective of the DST result.

Post-diuretic spot urine sodium assessment in acute heart failure: a retrospective analysis.

AIMS: To provide real-world data on post-diuretic spot urine sodium concentration (UNa) assessment in acute heart failure (AHF) and its implications for treatment. METHODS AND RESULTS: Automated query of the electronic medical record identified patients admitted to the cardiac intensive care unit of a single tertiary care hospital between November 2018 and December 2021, who received intravenous loop diuretics. Detailed manual chart review confirmed the AHF diagnosis. Stratification was performed based on whether post-diuretic UNa was assessed within 24 h of admission. AHF was confirmed in 340/380 identified patients. Post-diuretic UNa was assessed in 117 (34%), more frequently when ejection fraction was reduced and heart failure more advanced. Patients with versus without post-diuretic UNa assessment received higher doses of intravenous loop diuretics and more frequently acetazolamide and thiazide-like diuretics (p < 0.001 for all), resulting in similar urine output despite more advanced heart failure [2,488 mL (1,740-4,033 mL) vs. 2,400 mL (1,553-3,250 mL), respectively; p = 0.170]. Diuretic therapy remained more intense at discharge in the post-diuretic UNa group, with also a higher prescription rate of angiotensin-neprilysin inhibitors (p = 0.021). Serum creatinine increases/decreases were similarly frequent irrespectively from UNa assessment, with more dynamic changes observed in patients with UNa ≤ 80 mmol/L versus ≥ 81 mmol/L. After adjustments for baseline characteristics, the risk for death or heart failure readmission was similar in patients with versus without UNa assessment [HR (95%CI) = 1.43 (0.88-2.32); p = 0.150]. CONCLUSION: Post-diuretic UNa assessment in AHF was associated with more intense diuretic regimens, preserving urine output despite its use in a sicker population.