Mechanisms of Diuretic Resistance in Heart Failure, Aim 1

Summary

This study will employ a randomized order, double-blind, repeated measures dose ranging design. This design was chosen in order to generate multiple within-subject serial loop diuretic dose response exposures. The overall study schema will include 75 heart failure (HF) patients.

Eligibility

Inclusion Criteria:

* Clinical diagnosis of HF
* No plan for titration/change of heart failure medical or device therapies during the study period.
* Absence of non-elective hospitalizations in the previous 3 months.
* At optimal volume status by symptoms, exam, and dry weight
* Age \> 18 years

Exclusion Criteria:

* GFR \<20 ml/min/1.73m2 using the Chronic Kidney Disease- Epidemiology (CKD-EPI)equation or use of renal replacement therapies
* Use of any non-loop type diuretic in the last 14 days with the exclusion of low dose aldosterone antagonist (e.g., spironolactone or eplerenone ≤50 mg). Examples of non-loop diuretics include but may not be limited to acetazolamide (oral or IV, not ophthalmic), metolazone, Hydrochlorothiazide (HCTZ), chlorthalidone, chlorothiazide, indapamide, triamterene, amiloride, finerenone, spironolactone dose \> 50mg day, eplerenone \> 50mg/day,
* History of flash pulmonary edema requiring hospitalization and treatment with biphasic positive airway pressure or mechanical ventilation or a "brittle" volume sensitive HF phenotype such as an infiltrative or restrictive cardiomyopathy (i.e. amyloid cardiomyopathy, etc).
* Hemoglobin \< 8 g/dL
* Pregnant or breastfeeding
* Inability to give written informed consent or comply with study protocol or follow-up visits
* Chronic Urinary retention limiting ability to perform timed urine collection procedures

Conditions2

Interventions1

Locations1 site

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