Clinical screening tools for obstructive sleep apnea in a population with atrial fibrillation: a diagnostic accuracy trial.

STUDY OBJECTIVES: Although obstructive sleep apnea (OSA) is a known risk factor for atrial fibrillation (AF), there is a paucity of data around its diagnosis and management in patients with AF. The objectives of this study were to compare the diagnostic accuracy of commonly used OSA screening tools in an AF population, including a level 3 portable sleep study device, and to examine the epidemiology of OSA in a hospital cohort with AF. METHODS: One hundred seven patients with AF recruited from 2 tertiary centers underwent a panel of OSA screening tools and in-laboratory polysomnography in randomized order. RESULTS: Oxygen desaturation index derived from a level 3 portable sleep study device performed best for moderate to severe and severe OSA, with excellent diagnostic accuracy (area under the curve, 0.899; 95% confidence interval, 0.838-0.960 and area under the curve, 0.925; 95% confidence interval, 0.859-0.991, respectively). Sixty-seven patients (62.6%) were newly diagnosed with OSA (31.8% mild, 18.7% moderate, 12.1% severe). CONCLUSIONS: Undiagnosed OSA is highly prevalent in a hospital AF cohort. However, it is characterized by a relative paucity of symptoms, markedly limiting the usefulness of history or screening questionnaires. This is the first study to find that a level 3 home sleep study device shows excellent diagnostic accuracy in patients with AF. This finding may inform AF management guidelines. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Name: The validity and reliability of a portable device for the diagnosis of Obstructive Sleep Apnoea in patients with Atrial Fibrillation; URL:https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371024; Identifier: ACTRN12616001016426.

Targeting Cardiac Myocyte Na+-K+ Pump Function With ß3 Adrenergic Agonist in Rabbit Model of Severe Congestive Heart Failure.

BACKGROUND: Abnormally high cytosolic Na+ concentrations in advanced heart failure impair myocardial contractility. Stimulation of the membrane Na+-K+ pump should lower Na+ concentrations, and the ß3 adrenoceptor (ß3 AR) mediates pump stimulation in myocytes. We examined if ß3 AR-selective agonists given in vivo increase myocyte Na+-K+ pump activity and reverse organ congestion in severe heart failure (HF). METHODS: Indices for HF were lung-, heart-, and liver: body weight ratios and ascites after circumflex coronary artery ligation in rabbits. Na+-K+ pump current, Ip, was measured in voltage-clamped myocytes from noninfarct myocardium. Rabbits were treated with the ß3 AR agonists CL316,243 or ASP9531, starting 2 weeks after coronary ligation. RESULTS: Coronary ligation caused ascites in most rabbits, significantly increased lung-, heart-, and liver: body weight ratios, and decreased Ip relative to that for 10 sham-operated rabbits. Treatment with CL316,243 for 3 days significantly reduced lung-, heart-, and liver: body weight ratios and prevalence of ascites in 8 rabbits with HF relative to indices for 13 untreated rabbits with HF. It also increased Ip significantly to levels of myocytes from sham-operated rabbits. Treatment with ASP9531 for 14 days significantly reduced indices of organ congestion in 6 rabbits with HF relative to indices of 6 untreated rabbits, and it eliminated ascites. ß3 AR agonists did not significantly change heart rates or blood pressures. CONCLUSIONS: Parallel ß3 AR agonists-induced reversal of Na+-K+ pump inhibition and indices of congestion suggest pump inhibition is a useful target for treatment with ß3 AR agonists in congestive HF.

Chronic amiodarone-induced inhibition of the Na+-K+ pump in rabbit cardiac myocytes is thyroid-dependent: comparison with dronedarone.

OBJECTIVE: To examine the thyroid-dependence of the effect of amiodarone on the sarcolemmal Na(+)-K(+) pump, and the effect on the pump of dronedarone, a deiodinated amiodarone congener without influence on thyroid status. METHODS: New Zealand white rabbits underwent total thyroidectomy, sham thyroidectomy or thyroidectomy and concomitant oral amiodarone therapy. After 5 weeks, Na(+)-K(+) pump current was measured using the whole-cell patch-clamp technique in isolated ventricular myocytes. Pump current was also measured in myocytes isolated from a separate group of rabbits not subjected to thyroidectomy but treated with dronedarone, or placebo for 3 weeks. RESULTS: Treatment of thyroidectomised rabbits with amiodarone caused a significant prolongation of the corrected QT interval (QT(c)) and sinus cycle length. Na(+)-K(+) pump current measured in myocytes isolated from thyroidectomised rabbits was significantly lower than pump current in myocytes from sham-operated controls. However, treatment of thyroidectomised rabbits with amiodarone did not cause any additional decrease in pump current. Treatment with dronedarone caused prolongation of QT(c). However, it had no effect on Na(+)-K(+) pump current. CONCLUSIONS: The inhibitory effect of amiodarone on Na(+)-K(+) pump current is thyroid-dependent, whereas the effects on heart rate and QT(c) are at least partially mediated by thyroid-independent mechanisms. In contrast to its parent compound, dronedarone has no significant effects on the activity of the Na(+)-K(+) pump.