Characterized by periodic crescendo-decrescendo pattern of breathing alternating with central apneas, Central sleep apnea (CSA) with Cheyne-Stokes Breathing represents a highly prevalent, yet underdiagnosed comorbidity in chronic heart failure (CHF). A diverse body of evidence demonstrates increased morbidity and mortality in the presence of CSB. CSB has been described in both CHF patients with preserved and reduced ejection fraction, regardless of drug treatment. Risk factors for CSB are older age, male gender, high BMI, atrial fibrillation and hypocapnia.The pathophysiology of CSB has been explained by the loop gain theory, where a controller (the respiratory center) and a plant (the lungs) are operating in a reciprocal relationship (negative feedback) to regulate a key parameter (partial pressure of carbon dioxide (pCO)). The temporal interaction between these elements is dependent on the circulatory delay. Increased chemosensitivity/chemoresponsiveness of the respiratory center and/or augmented ascending non- CO stimuli from the C-fibers in the lungs (interstitial pulmonary edema), overly efficient ventilation when breathing at low volumes and prolonged circulation time are involved. An alternative hypothesis of CSB being an adaptive response of the failing heart has its merits as well. The clinical manifestation of CSB is usually poor, lacking striking symptoms and complaints. Witnessed apneas and snoring are infrequently reported by the sleep partner. Sometimes patients may report poor sleep quality with frequent awakenings, paroxysmal nocturnal dyspnea and frequent urination at night. Standard instrumental and laboratory studies, performed in CHF patients, may present clues to the presence of CSB. Concentric remodeling of the left ventricle and dilated left atrium (echocardiography), high BNP and C-reactive protein levels, increased ventilation-carbon dioxide output (VEVCO) and lower end-tidal CO (cardiopulmonary exercise testing), reduced diffusion capacity (pulmonary function testing) and hypocapnia (blood-gas analysis) may indicate the presence of CSB.CSB and cardiovascular disease are probably linked through bidirectional causality. Cyclic variations in heart rate, blood pressure, respiratory volume, partial pressure of arterial oxygen (pO) and pCO lead to sympathetic-adrenal activation. The latter worsens ventricular energetism and survival of cardiomyocytes and exerts antiarhythmogenic effects. It causes cardiac remodeling, potentiating the progression and the lethal outcome in CHF patients. Several treatment modalities have been proposed in CSB. The most commonly used are continuous positive airway pressure (CPAP), adaptive servoventilation (ASV) and nocturnal home oxygen therapy (HOT). Novel therapies like nocturnal supplemental CO and phrenic nerve stimulation are being tested recently. The current treatment recommendations (by the American Academy of Sleep Medicine) are for CPAP and HOT as standard therapies, while ASV is an option only in patients with EF > 45%. BPAP (bilevel device) remains an ...

Continuous positive airway pressure (CPAP) improves autonomic activity in patients with chronic heart failure (CHF) and central sleep apnoea (CSA), but its effect on heart rate variability (HRV) during therapy has not been reported. We hypothesized that CPAP may decrease HRV, despite its beneficial effects on sympathetic overactivation, due to the expected stabilization of breathing. Sixty-seven CHF patients underwent polysomnography (PSG). Ten of them presented with CSA (age 66.1±8.5 years, apnoea-hypopnea index [AHI]=57.6±23.3, central AHI [cAHI]=41.6±24.6 [mean±SD]) and were subjected to a second PSG with manual CPAP titration. Beat-to-beat heart intervals for a 6-hour period of sleep were extracted from each recording and HRV was analysed. CPAP significantly reduced AHI (AHI=23.1±18.3 P=.004). Standard deviation of normal-normal interbeat interval (SDNN) (61.5±29.0 vs 49.5±19.3 ms, P=.021), root mean square of successive differences (RMSSD) (21.8±9.2 vs 16.4±7.1 ms, P=.042), total power (lnTP=7.8±1.1 vs 7.4±0.8 ms , P=.037), low frequency power (lnLF=5.5±1.5 vs 5.0±1.4 ms , P=.003) and high frequency power (lnHF=4.6±1.0 vs 4.0±1.0 ms , P=.024) were decreased. There was a strong correlation between the decrease in AHI and the decrease in lnHF (Spearman's ρ=.782). CPAP leads to a decrease in spectral and time domain parameters of HRV during therapy in CHF patients with CSA. These changes are best explained by the effect which CPAP-influenced breathing pattern and lowered AHI exert on HRV.

Background: Pharmacological treatment of depression is currently led by the trial and error principle mainly because of lack of reliable biomarkers. Earlier fi ndings suggest that baseline alpha power and asymmetry could diff erentiate between responders and non-responders to specifi c antidepressants. Aim: The current study investigated quantitative electroencephalographic (QEEG) measures before and early in treatment as potential response predictors to various antidepressants in a naturalistic sample of depressed patients. We were aiming at developing markers for early prediction of treatment response based on diff erent QEEG measures. Materials and methods: EEG data from 25 depressed subjects were acquired at baseline and after one week of treatment. Mean and total alpha powers were calculated at eight electrode sites F3, F4, C3, C4, P3, P4, O1, O2. Response to treatment was defi ned as 50% decrease in MADRS score at week 4. Results: Mean P3 alpha predicted response with sensitivity and specifi city of 80%, positive and negative predictive values of 92.31% and 71.43%, respectively. The combined model of response prediction using mean baseline P3 alpha and mean week 1 C4 alpha values correctly identifi ed 80% of the cases with sensitivity of 84.62%, and specifi city of 71.43%. Conclusions: Simple QEEG measures (alpha power) acquired before initiation of antidepressant treatment could be useful in outcome prediction with an overall accuracy of about 80%. These fi ndings add to the growing body of evidence that alpha power might be developed as a reliable biomarker for the prediction of antidepressant response.

Chronic heart failure (CHF) is a major health problem associated with increased mortality, despite modern treatment options. Central sleep apnea (CSA)/Cheyne-Stokes breathing (CSB) is a common and yet largely under-diagnosed co-morbidity, adding significantly to the poor prognosis in CHF because of a number of acute and chronic effects, including intermittent hypoxia, sympathetic overactivation, disturbed sleep architecture and impaired physical tolerance. It is characterized by repetitive periods of crescendo-decrescendo ventilatory pattern, alternating with central apneas and hypopneas. The pathogenesis of CSA/CSB is based on the concept of loop gain, comprising three major components: controller gain, plant gain and feedback gain. Laboratory polysomnography, being the golden standard for diagnosing sleep-disordered breathing (SDB) at present, is a costly and highly specialized procedure unable to meet the vast diagnostic demand. Unlike obstructive sleep apnea, CSA/CSB has a low clinical profile. Therefore, a reliable predictive system is needed for identifying CHF patients who are most likely to suffer from CSA/CSB, optimizing polysomnography use. The candidate predictors should be standardized, easily accessible and low-priced in order to be applied in daily medical routine. The present review focuses on a pathophysiological approach to the selection of some predictors based on parameters reflecting the etiology, the pathogenesis and the consequences of CSA/CSB in CHF.

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