Acute improvement of pulmonary hemodynamics does not alleviate Cheyne-Stokes respiration in chronic heart failure-a randomized, controlled, double-blind, crossover trial.

OBJECTIVES: This randomized, controlled trial aimed to investigate whether acute improvement of pulmonary congestion would reduce the severity of Cheyne-Stokes respiration (CSR) in patients with chronic heart failure (CHF). METHODS: Twenty-one consecutive patients with CHF and CSR (apnea-hypopnea index [AHI] ≥15/h) underwent right heart catheterization with titration of intravenous (IV) glyceryltrinitrate (GTN) to a maximum tolerable dosage and inhalation of iloprost 10 µg/mL after a washout phase. Maximum tolerable dosages of GTN and iloprost were randomly applied during full cardiorespiratory polysomnography within two split-night procedures and compared with IV or inhaled sodium chloride (NaCl) 0.9 %, respectively. RESULTS: GTN (6.2 ± 1.5 mg/h) and iloprost significantly lowered \mean pulmonary artery pressure (20.1 ± 9.0 to 11.6 ± 4.2 mmHg, p < 0.001 and 16.9 ± 7.9 to 14.2 ± 6.4 mmHg, p < 0.01, respectively). Pulmonary capillary wedge pressure was only reduced by GTN (14.0 ± 5.6 to 7.2 ± 3.9 mmHg, p < 0.001), and there was no significant change in the cardiac index. Sleep studies revealed no significant improvement in markers of CSR severity, including AHI, central apnea index, and CSR cycle length following GTN or iloprost treatment. Significant decreases in blood pressure, mean oxygen saturation, and S3 sleep were documented during GTN infusion. CONCLUSIONS: Acute improvement of pulmonary congestion by GTN had no immediate impact on CSR severity. Future investigations must therefore include longer treatment periods and treatment regimens that have positive, rather than negative, additional effects on peripheral and central chemoreceptors and sleep structure. TRIAL REGISTRATION: German Clinical Trial Registry-ID:DRKS00000467 ( www.germanctr.de ).

C-reactive protein is elevated in heart failure patients with central sleep apnea and Cheyne-Stokes respiration.

BACKGROUND: Manifestation of central sleep apnea (CSA) with Cheyne-Stokes respiration is of major prognostic impact in chronic heart failure (CHF). Inflammatory processes have been linked to a progression of cardiovascular diseases, including heart failure. While an association of C-reactive protein (CRP) levels to obstructive sleep apnea has been documented before, there is a lack of information regarding variation of CRP levels in patients with CSA. OBJECTIVES: The objective of this study was to investigate a potential association of CRP levels to CSA severity in CHF patients. METHODS: High sensitivity CRP levels were analyzed in 966 patients with CHF (BMI 26.3 ± 4.6, New York Heart Association class 2.6 ± 0.5, left ventricular ejection fraction 29.4 ± 7.9%, N-terminal pro-brain natriuretic peptide, NT-proBNP, level 2,209 ± 3,315 pg/ml) without sleep-disordered breathing (SDB; Apnea-Hypopnea Index, AHI, <5/h) or various degrees of CSA, documented by in-hospital cardiorespiratory polygraphy or polysomnography. RESULTS: The CRP concentration in CHF patients was 0.550 ± 0.794 mg/dl in patients without SDB (AHI 0-4/h, n = 403) versus 0.488 ± 0.708 mg/dl in patients with mild CSA (AHI 5-14/h, n = 123, p = n.s.) and 0.660 ± 0.963 mg/dl in patients with moderate CSA (AHI 15-29/h, n = 160, p = n.s.). In patients with severe CSA (AHI ≥ 30/h, n = 280), significantly higher CRP concentrations were documented (0.893 ± 1.384 mg/dl, p < 0.05). Stepwise regression analysis revealed AHI, NT-proBNP and heart rate to be independently associated with elevated CRP levels. CONCLUSION: Severe CSA in CHF patients is associated with elevated levels of CRP, a systemic marker of inflammation and cardiovascular risk. This might explain in part the negative prognostic impact of CSA in these patients.

Hypotensive effects of positive airway pressure ventilation in heart failure patients with sleep-disordered breathing.

INTRODUCTION: Obstructive sleep apnoea (OSA) as well as central sleep apnoea (CSA) are highly prevalent in heart failure (HF) patients. Positive airway pressure (PAP) therapy is usually intended to treat OSA and CSA. The aim of the present study was to investigate immediate hemodynamic effects of PAP therapy in these patients. MATERIALS AND METHODS: In 61 consecutive HF patients (NYHA ≥ II, EF ≤ 45%) with moderate to severe OSA or CSA (AHI ≥ 15/h) blood pressure (BP) and heart rate (HR) response to PAP therapy initiation was investigated during mask fitting with patients being awake and in supine position. While applying an endexspiratory pressure of 5.8 ± 0.9 cm H(2)O, there was a significant decrease in systolic (-8.9 ± 12.1 mmHg, p < 0.001) and diastolic BP (-5.1 ± 9.2 mmHg, p < 0.001) without a change in HR (p = n.s.). RESULTS: At least a transient drop in mean arterial pressure ≤70 mmHg was seen in 10% of these patients. Logistic regression analysis revealed a significant impact of baseline BP on potential BP drops: lower baseline BP was associated with BP drops. CONCLUSION: PAP therapy may cause unexpected hypotension especially in patients with low baseline BP as seen in HF patients treated according to current guidelines. Whether these hypotensive effects sustain, cause any harm to the patients and/or is responsible for non-acceptance or non-adherence of PAP therapy needs to be determined.

Pulse transit time: validation of blood pressure measurement under positive airway pressure ventilation.

PURPOSE: The objective of the present study was to validate noninvasive, continuous blood pressure (BP) measurement using pulse transit time (PTT) to represent absolute values and detect BP changes under continuous positive airway pressure (CPAP) treatment. METHODS: We applied CPAP to 78 patients of a cardiological sleep lab using 0 (baseline), 4, 8, and 12 cmH(2)O for 10 min at every level and measured BP simultaneous via PTT-based method and standard oscillometric method (OM). RESULTS: Quality of signal perception was acceptable to convert PTT into BP values in 64 patients (82%). When comparing both methods, we found a strong linear correlation of systolic and diastolic BP (baseline, r = 0.94 for systolic BP; r = 0.95 for diastolic BP, p < 0.001) while no significant differences between absolute values obtained with OM and PTT measurement. Mean bias at baseline was 4.1 ± 3.2 mmHg for systolic BP and 2.3 ± 2.2 mmHg for diastolic BP. With increasing CPAP levels, PTT and OM measurements differed continuously up to a systolic difference of 6.6 ± 4.9 mmHg and a diastolic difference of 4.4 ± 3.5 mmHg. There was no definite trend of PTT method to either over- or underestimate BP. CONCLUSIONS: We found that PTT- and OM-based BP results are closely correlated while applying CPAP over a period of 40 min. With higher CPAP level, bias between both methods increased.