Predicting Successful Sleep Apnea Treatment With Acetazolamide in Heart Failure Patients

Not Applicable

Completed

Conditions: Heart Failures

Interventions: Drug: Placebo
Drug: Acetazolamide

Registration Number: NCT01377987

Lead Sponsor: David Andrew Wellman

Brief Summary: The ultimate goal is to improve our understanding of the pathophysiology and resistance to effective treatment of sleep disordered breathing in patients with heart failure, with a focus on selecting patients that will benefit specifically from acetazolamide treatment.

The study addresses three primary hypotheses: 1) Acetazolamide treatment will reduce the apnea-hypopnea index and improve markers of heart-failure severity in heart-failure patients with sleep apnea. 2) Acetazolamide will provide the greatest improvement in patients with the most severe ventilatory control instability (strongest chemoreflex response to carbon dioxide; highest loop gain). 3) Acetazolamide will act primarily via stabilizing ventilatory control (reducing loop gain), rather than via improvement to upper airway anatomy, pulmonary congestion, and cardiac function.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 29

Inclusion Criteria

Not provided

Exclusion Criteria

severe obstructive respiratory disease
unstable heart failure status
recent use of positive airway pressure therapy
current use of opioids, benzodiazepines
severe kidney disease
severe anemia

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sugar pill	Placebo	-
Acetazolamide	Acetazolamide	-

Primary Outcome Measures

Name	Time	Method
The Severity of Sleep Disordered Breathing (Apnea-hypopnea Index, AHI)	1 week	The frequency of apneas and hypopneas (apnea-hypopnea index) was assessed. The primary measure was the value for non-REM supine sleep. A higher value indicates more severe sleep apnea. A value above 15 indicates the presence of moderate-to-severe sleep apnea.

Secondary Outcome Measures

Name	Time	Method
Ventilatory Chemoreflex Sensitivity, "Loop Gain" Using Carbon Dioxide Pulses	1 week	Chemoreflex "loop gain" was assessed according to Sands SA et al AJRCCM 2017 Jan 15;195(2):237-246. Loop gain is a unitless ratio measure that describes the magnitude of the increase in ventilation that occurs in response to a prior reduction in ventilation ("disturbance") and has units of L/min per L/min. A larger value indicates a more sensitive and unstable control system predisposing to oscillatory breathing. Loop gain was measured on the time scale of 1 min (i.e. response to a 1 cycle/min sinusoidal disturbance, referred to as "LG1"). The procedure involved brief administration of 7% carbon dioxide in air for 0.5 min ("pulses"); tests were repeated every 3 min for 30 min while measuring ventilation and carbon dioxide levels at the nose with patients awake and supine. measured using 0.5 min pulses of carbon dioxide.
Sympathetic Activity (Urinary Norepinephrine)	1 week	Urinary norepinephrine levels overnight
Left-atrial Volume	1 week	Left-atrial volume index, echocardiography, bi-plane method. Lower values were considered a favorable outcome. We considered values ≤28 mL/m\^2 to indicate normal left atrial volume. Values indicating graded left atrial enlargement were described as follows: mild (29-33 mL/m\^2), moderate (34-39 mL/m\^2), severe (≥40 mL/m\^2).
Brain Natriuretic Peptide (NT-proBNP)	1 week	Brain natriuretic peptide (NT-proBNP) in morning
Pittsburgh Sleep Quality Index	1 week	Pittsburgh Sleep Quality Index is a measure of self-reported sleep quality containing 19 questions that make up 7 component scores that are added to provide a total score. Total scores range from 0-21 (units on a scale) with higher scores representing reduced sleep quality. A score of 5 or more is interpreted as reduced sleep quality. The total score is reported.