Brian Patt

Endothelial Dysfunction in the Microcirculation of Patients with Obstructive Sleep Apnea

RATIONALE Obstructive sleep apnea (OSA) is a risk factor for cardiovascular disease. We hypothesized that patients with OSA and no cardiovascular disease have oxidant-related microcirculatory endothelial dysfunction. OBJECTIVES To evaluate the microcirculation in OSA. METHODS This study included seven patients with OSA and seven age- and weight-matched control subjects (mean age, 38 yr; mean body mass index, 32.5 kg/m²). All participants were free of cardiovascular risk factors. Participants received measurement of brachial artery flow-mediated dilation and forearm subcutaneous biopsy. Patients underwent repeated tests 12 weeks after treatment. Microcirculatory endothelial cells were isolated, and immunohistochemistry staining for peroxynitrite in the microcirculation was performed. MEASUREMENTS AND MAIN RESULTS Flow-mediated dilation was lower in patients than in control subjects at baseline (mean ± SEM: 5.7 ± 0.5 vs. 9.5 ± 0.6; P = 0.02) and increased after treatment (5.7-7.3; change, 1.7 ± 0.6; P = 0.04). Microcirculatory peroxynitrite deposit was higher in patients compared with control subjects (44.0 ± 1.6 vs. 21.8 ± 1.9 stain density units; P < 0.001) and decreased after treatment from 44.0 to 30.5 stain density units (change, -13.5 ± 2.9; P = 0.009). In patients, transcription of endothelial nitric oxide synthase decreased from 5.2 to -1.3 after treatment (change, 6.5 ± 2.5; P = 0.05), and transcription of superoxide dismutase1 decreased from -4.0 to -12.3 after treatment (change, -8.3 ± 2.1; P = 0.01). These changes persisted after adjustment for weight and underlying severity of OSA. CONCLUSIONS This is the first direct evaluation of the microcirculation in OSA. Patients with OSA with low cardiovascular risk status had increased oxidant production in the microcirculation and endothelial dysfunction, both of which improved with treatment. Endothelial nitric oxide synthase transcription decreased with treatment.

In-hospital Testing for Sleep-disordered Breathing in Hospitalized Patients With Decompensated Heart Failure: Report of Prevalence and Patient Characteristics

BACKGROUND Sleep-disordered breathing (SDB) is present in more than 50% of ambulatory patients with chronic heart failure. The prevalence and type of SDB in hospitalized patients with acutely decompensated heart failure (ADHF) are not known. METHODS AND RESULTS In-hospital sleep studies were performed on consecutive patients with ADHF who were not previously tested for SDB. A total of 395 consecutive patients with ADHF underwent successful sleep study recording during hospitalization. A total of 298 patients (75%, 95% CI [71-80%] had SDB; of these, 226 (57%, 95% CI [52-62]) had predominantly obstructive SDB and 72 (18%, 95% CI [14-22]) had predominantly central SDB. Only 25% (95% CI 20-29%) of patients were free of SDB. Validation polysomnography between 6 and 8 weeks after discharge on a subgroup of unselected patients with obstructive SDB revealed a 100 % positive predictive value (95% CI 94-100%) for obstructive sleep apnea (OSA). CONCLUSIONS Similar to stable chronic heart failure, ADHF is associated with a high prevalence of SDB. The prevalence of predominantly obstructive SDB exceeded that of predominantly central SDB in ADHF patients. The presence of obstructive SDB during hospitalization predicted a diagnosis of OSA on polysomnography.

Obstructive sleep apnea: the new cardiovascular disease. Part I: obstructive sleep apnea and the pathogenesis of vascular disease

Obstructive sleep apnea (OSA) is increasingly recognized as a novel cardiovascular risk factor. OSA is implicated in the pathogenesis of hypertension, left ventricular dysfunction, coronary artery disease and stroke. OSA exerts its negative cardiovascular consequences through its unique pattern of intermittent hypoxia. Endothelial dysfunction, oxidative stress, and inflammation are all consequences of OSA directly linked to intermittent hypoxia and critical pathways in the pathogenesis of cardiovascular disease in patients with OSA. This review will discuss the known mechanisms of vascular dysfunction in patients with OSA and their implications for cardiovascular disease.

In-Hospital Treatment of Obstructive Sleep Apnea During Decompensation of Heart Failure

BACKGROUND Treatment of obstructive sleep apnea (OSA) in outpatients with systolic heart failure improves cardiac function. We evaluated the impact of immediate inpatient diagnosis and treatment of OSA in hospitalized patients with acutely decompensated heart failure (ADHF) on in-hospital cardiac outcomes. METHODS A pilot randomized controlled trial was conducted in an academic heart hospital. Patients with ADHF underwent an attended in-hospital sleep study within 2 days of hospital admission to establish the diagnosis of sleep-disordered breathing. The participants were 46 consecutive patients with ADHF who had OSA (apnea-hypopnea index [AHI], >or= 15 events per hour). Participants were randomly assigned to either the intervention arm (n = 23), with in-hospital treatment of OSA using auto-adjusting positive airway pressure along with standard treatment of ADHF, or to the control arm (n = 23), in which they received only standard treatment for ADHF. The primary outcome was the change in left ventricular ejection fraction (LVEF) 3 nights postrandomization. RESULTS The change in LVEF from baseline to 3 days postrandomization in the intervention arm was significantly superior to that of the control group. The difference in LVEF improvement was 4.6% (p = 0.03). LVEF increased in the intervention group by 4.5% (SE, 1.7%). The LVEF change in the control arm was--0.3% (SE, 1.5%). The difference in LVEF improvement between the two groups persisted after adjustment for baseline LVEF, type of cardiomyopathy, BMI, AHI, and sex. CONCLUSIONS An approach of early identification and in-hospital treatment of OSA in patients with ADHF is feasible and resulted in improvement in systolic function. The impact of this approach on out-of-hospital outcomes requires further investigation. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00701038.

Cardiac Effects of Continuous and Bilevel Positive Airway Pressure for Patients With Heart Failure and Obstructive Sleep Apnea: A Pilot Study

BACKGROUND Obstructive sleep apnea (OSA) is prevalent in patients with heart failure. Treatment with continuous positive airway pressure (CPAP) improves systolic function in patients with heart failure. Bilevel positive airway pressure (PAP) is another treatment modality for OSA. The intermediate-term effect of bilevel PAP on left ventricular ejection fraction (LVEF) in patients with stable heart failure and OSA has not been compared to the effect of CPAP. METHODS In this pilot randomized controlled trial, patients with stable systolic dysfunction and newly diagnosed OSA (n = 24) were randomized to receive either CPAP or bilevel PAP. Titration was done in the sleep laboratory using a CPAP-based algorithm. Primary outcome was the improvement in LVEF after 3 months of treatment. Other measurements included 6-min walk test, Epworth sleepiness scale score, and the Minnesota Living With Heart Failure questionnaire. RESULTS Bilevel PAP increased LVEF 7.9% (LVEF percentage scale) more than CPAP (95% confidence interval [CI], 2.3 to 13.4; p = 0.01). In the bilevel PAP group, LVEF increased 8.5% (95% CI, 3.7 to 13.4; p = 0.002). In the CPAP group, LVEF did not change significantly (0.5%; 95% CI, - 2.7 to 3.7; p = 0.7). The difference in LVEF improvement between the two groups was still significant after adjustment for adherence, level of treatment positive pressure, body mass index, and severity of OSA. CONCLUSION This pilot randomized controlled trial suggests that bilevel PAP is superior to CPAP in improving LVEF in patients with systolic dysfunction and OSA. Larger trials are required to evaluate the mechanism behind this effect.