Matthew T. Naughton

Influence of Pulmonary Capillary Wedge Pressure on Central Apnea in Heart Failure

BACKGROUND Recent studies suggest that acute pulmonary congestion induces hyperventilation and that hyperventilation-related hypocapnia leads to ventilatory control instability and central sleep apnea. Whether chronic pulmonary congestion due to congestive heart failure (CHF) is associated with central apnea is unknown. We hypothesized that CHF patients with central apnea would have greater pulmonary capillary wedge pressure (PCWP) than patients without central apnea and that PCWP would correlate with central apnea severity. METHODS AND RESULTS Seventy-five stable CHF patients underwent right heart catheterization and, on the basis of overnight sleep studies, were divided into central apnea (n=33), obstructive apnea (n=20), or nonapnea groups (apnea-hypopnea index [AHI] <5 events per hour). Mean PCWP was significantly greater in the central than in the obstructive and nonapnea groups (mean+/-SEM [range]: 22. 8+/-1.2 [11 to 38] versus 12.3+/-1.2 [4 to 21] versus 11.5+/-1.5 [3 to 28] mm Hg, respectively; P<0.001). Within the central apnea group, PCWP correlated with the frequency and severity of central apnea (AHI: r=0.47, P=0.006) and degree of hypocapnia (PaCO2: r=-0.42, P=0. 017). Intensive medical therapy in 7 patients with initially high PCWP and central apneas reduced both PCWP (29.0+/-2.6 [20 to 38] to 22.0+/-1.8 [17 to 27] mm Hg; P<0.001) and central apnea frequency (AHI) (38.5+/-7.7 [7 to 62] to 18.5+/-5.3 [1 to 31] events per hour; P=0.005). CONCLUSIONS PCWP is elevated in CHF patients with central apneas compared with those with obstructive apnea or without apnea. Moreover, a highly significant relationship exists between PCWP, hypocapnia, and central apnea frequency and severity.

Updating the minimal important difference for six-minute walk distance in patients with chronic obstructive pulmonary disease.

OBJECTIVE To establish the minimal important difference (MID) for the six-minute walk distance (6MWD) in persons with chronic obstructive pulmonary disease (COPD). DESIGN Analysis of data from an observational study using distribution- and anchor-based methods to determine the MID in 6MWD. SETTING Outpatient pulmonary rehabilitation program at 2 teaching hospitals. PARTICIPANTS Seventy-five patients with COPD (44 men) in a stable clinical state with mean age 70 years (SD 9 y), forced expiratory volume in one second 52% (SD 21%) predicted and baseline walking distance 359 meters (SD 104 m). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Participants completed the six-minute walk test before and after a 7-week pulmonary rehabilitation program. Participants and clinicians completed a global rating of change score while blinded to the change in 6MWD. RESULTS The mean change in 6MWD in participants who reported themselves to be unchanged was 17.7 meters, compared with 60.2 meters in those who reported small change and 78.4 meters in those who reported substantial change (P=.004). Anchor-based methods identified an MID of 25 meters (95% confidence interval 20-61 m). There was excellent agreement with distribution-based methods (25.5-26.5m, kappa=.95). A change in 6MWD of 14% compared with baseline also represented a clinically important effect; this threshold was less sensitive than for absolute change (sensitivity .70 vs .85). CONCLUSIONS The MID for 6MWD in COPD is 25 meters. Absolute change in 6MWD is a more sensitive indicator than percentage change from baseline. These data support the use of 6MWD as a patient-important outcome in research and clinical practice.

The six-minute walk test: a useful metric for the cardiopulmonary patient

Measurement of exercise capacity is an integral element in assessment of patients with cardiopulmonary disease. The 6‐min walk test (6MWT) provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions. A distance less than 350 m is associated with increased mortality in chronic obstructive pulmonary disease, chronic heart failure and pulmonary arterial hypertension. Desaturation during a 6MWT is an important prognostic indicator for patients with interstitial lung disease. The 6MWT is sensitive to commonly used therapies in chronic obstructive pulmonary disease such as pulmonary rehabilitation, oxygen, long‐term use of inhaled corticosteroids and lung volume reduction surgery. However, it appears less reliable to detect changes in clinical status associated with medical therapies for heart failure. A change in walking distance of more than 50 m is clinically significant in most disease states. When interpreting the results of a 6MWT, consideration should be given to choice of predictive values and the methods by which the test was carried out.

Sleep apnea in congestive heart failure.

Sleep-related breathing disorders, including obstructive sleep apnea (OSA) and Cheyne-Stokes respiration with central sleep apnea (CSR-CSA), commonly occur in patients with congestive heart failure (CHF). In this setting they can have adverse pathophysiologic effects on the cardiovascular system. OSA may lead to development or progression of left ventricular (LV) dysfunction by increasing LV afterload through the combined effects of elevations in systemic blood pressure and a generation of exaggerated negative intrathoracic pressure, and by activating the sympathetic nervous system through the influence of hypoxia and arousals from sleep. Abolition of OSA by continuous positive airway pressure (CPAP) can improve cardiac function in patients with CHF. In contrast to OSA, CSR-CSA is likely a consequence rather than a cause of CHF. Here, pulmonary congestion causes hyperventilation by stimulating pulmonary irritant receptors. This leads to reductions in PaCO2 below the apneic threshold during sleep, precipitating posthyperventilatory central apneas. CSR-CSA is associated with increased mortality in CHF, probably because of sympathetic nervous system activation caused by recurrent apnea-induced hypoxia and arousals from sleep. Treatment of CSR-CSA by supplemental O2, theophylline, and CPAP can alleviate central apneas. Of these treatments, however, only CPAP has been shown to improve cardiac function and symptoms of heart failure. We conclude that effective treatments of OSA and CSR-CSA may prove to be useful adjuncts to the standard pharmacologic therapy of patients with CHF.

Increased long-term mortality in heart failure due to sleep apnoea is not yet proven

Previous small-scale studies of the effect of sleep-disordered breathing (SDB) on prognosis in congestive heart failure (CHF) are either lacking or conflicting. The aim of this study was to assess the impact of the presence and type of SDB on mortality in a patient group with severe CHF referred to a specialised heart failure centre. Out of 78 patients ((mean±sd) 53±9 yrs, left ventricular ejection fraction 19.9±7.2% and pulmonary capillary wedge pressure 16.5±8.3 mmHg) followed-up over a median period of 52 months, 29% had no apnoea (CHF‐N), 28% had obstructive sleep apnoea (CHF‐OSA) and 42% had central sleep apnoea (CHF‐CSA). At 52 months, their overall mortality was 40%, and combined mortality and transplantation was 72%. Mortality rates were similar between the three apnoea groups. Survivors had a similar prevalence of SDB (71%) as the nonsurvivors (70%). Although a significant increase in mortality was evident at 500 days in those patients with either CHF‐SDB or CHF‐CSA as compared with CHF‐N, this was not significant at final follow-up (52 months) using Kaplan Meier analysis. Multivariate analysis identified transplantation but not SDB type or severity as a significant predictor of survival. In conclusion, sleep-disordered breathing impacts upon early (500 day), but not long-term (52 month), mortality in a specialised heart failure centre.

A Randomized Controlled Trial of Nurse-led Care for Symptomatic Moderate–Severe Obstructive Sleep Apnea

RATIONALE Obstructive sleep apnea (OSA) is a prevalent disease. Often limited clinical resources result in long patient waiting lists. Simpler validated methods of care are needed. OBJECTIVES To demonstrate that a nurse-led model of care can produce health outcomes in symptomatic moderate-severe OSA not inferior to physician-led care. METHODS A randomized controlled multicenter noninferiority clinical trial was performed. Of 1,427 potentially eligible patients at 3 centers, 882 consented to the trial. Of these, 263 were excluded on the basis of clinical criteria. Of the remaining 619, 195 met home oximetry criteria for high-probability moderate-severe OSA and were randomized to 2 models of care: model A, the simplified model, using home autoadjusting positive airway pressure to set therapeutic continuous positive airway pressure (CPAP), with all care supervised by an experienced nurse; and model B, involving two laboratory polysomnograms to diagnose and treat OSA, with clinical care supervised by a sleep physician. The primary end point was change in Epworth Sleepiness Scale (ESS) score after 3 months of CPAP. Other outcome measures were collected. MEASUREMENTS AND MAIN RESULTS For the primary outcome change in ESS score, nurse-led management was no worse than physician-led management (4.02 vs. 4.15; difference, -0.13; 95% confidence interval: -1.52, 1.25) given a prespecified noninferiority margin of -2 for the lower 95% confidence interval. There were also no differences between both groups in CPAP adherence at 3 months or other outcome measures. Within-trial costs were significantly less in model A. CONCLUSIONS A simplified nurse-led model of care has demonstrated noninferior results to physician-directed care in the management of symptomatic moderate-severe OSA, while being less costly. Clinical trial registered with http://www.anzctr.org.au (ACTRN012605000064606).

Effect of Continuous Positive Airway Pressure on Mitral Regurgitant Fraction and Atrial Natriuretic Peptide in Patients With Heart Failure

OBJECTIVES We sought to determine the effects of continuous positive airway pressure (CPAP) on mitral regurgitant fraction (MRF) and plasma atrial natriuretic peptide (ANP) concentration in patients with congestive heart failure (CHF). BACKGROUND In patients with CHF, elevated plasma ANP concentration is associated with elevated cardiac filling pressures. Secondary mitral regurgitation may contribute to elevation in plasma ANP concentration in patients with CHF. Because CPAP reduces transmural cardiac pressures and left ventricular (LV) volume, we hypothesized that long-term CPAP application would decrease the MRF and plasma ANP concentration in patients with CHF and Cheyne-Stokes respiration with central sleep apnea (CSR-CSA). METHODS Seventeen patients with CHF and CSR-CSA underwent baseline assessments of plasma ANP concentration and left ventricular ejection fraction (LVEF) and MRF by radionuclide angiography. They were then randomized to receive nocturnal CPAP plus optimal medical therapy (n = 9) or optimal medical therapy alone (n = 8) for 3 months and were then reassessed. RESULTS In the CPAP-treated group, LVEF increased from (mean +/-SEM) 20.2 +/- 4.2% to 28.2 +/- 5.3% (p < 0.02); MRF decreased from 32.8 +/- 7.7% to 19.4 +/- 5.5% (p < 0.02); and plasma ANP concentration decreased from 140.9 +/- 20.8 to 103.9 +/- 17.0 pg/ml (p < 0.05). The control group experienced no significant changes in LVEF, MRF or plasma ANP concentration. Among all patients, the change in plasma ANP concentration from baseline to 3 months correlated significantly with the change in MRF (r = 0.789, p < 0.0002). CONCLUSIONS In patients with CHF, CPAP-induced reductions in MRF and plasma ANP concentration in association with improvements in LVEF indicate improved cardiac mechanics. Our findings also suggest that reductions in plasma ANP concentration were at least partly due to reductions in MRF.

Raised Sympathetic Nerve Activity in Heart Failure and Central Sleep Apnea Is Due to Heart Failure Severity

Background—Congestive heart failure (CHF) patients with central sleep apnea (CHF-CSA) have elevated plasma norepinephrine (NE) compared with CHF patients without apnea (CHF-N). Patients with CHF-CSA also demonstrate higher mean pulmonary artery pressure (PAP), which is suggestive of worse cardiac function. Whether CSA contributes to chronic elevation of sympathetic nerve activity or is associated with more severe CHF remains unknown. We measured awake total body and cardiac NE spillover and related these to measurements of cardiac hemodynamics and apnea severity in CHF patients with CSA, with normal breathing, and with obstructive sleep apnea (CHF-OSA). Methods and Results—A total of 55 CHF patients underwent right heart catheterization and measurements of total body and cardiac NE spillover using NE radioisotope dilution methodology. After polysomnography, patients were grouped by apnea type: 19 were CHF-N, 15 were CHF-OSA, and 21 were CHF-CSA. Compared with the CHF-N and CHF-OSA groups, the CHF-CSA group had significantly higher total body NE spillover (4.62±0.56 versus 4.47±0.54 versus 6.95±0.89 nmol/min, respectively;P =0.03), cardiac NE spillover (0.25±0.05 versus 0.21±0.05 versus 0.42±0.06 nmol/min, respectively;P =0.02) and mean PAP (23.5±2.4 versus 21.2±0.8 versus 30.4±0.2 mm Hg, respectively;P <0.02). However, controlling for severity of CHF resulted in no significant differences in NE kinetics among the 3 groups. In a stepwise regression, only mean PAP independently correlated with total body (r =0.33, P =0.03) and cardiac NE spillover (r =0.44, P =0.002). Sleep apnea severity bore no relationship to markers of sympathetic nerve activity. Conclusion—Total body and cardiac sympathetic nerve activity are elevated in CHF-CSA compared with CHF-OSA and CHF-N patients and are related to heart failure not apnea severity.

Effect of moderate alcohol upon obstructive sleep apnoea

Moderate-to-large quantities of alcohol are known to aggravate severe obstructive sleep apnoea (OSA), however, the reported effects of moderate alcohol consumption upon mild-to-moderate OSA are inconsistent. Given the reported benefits of moderate alcohol consumption on cardiovascular mortality, recommendations regarding the management of patients with OSA are difficult to formulate. The aim of this study was to evaluate the effects of moderate alcohol on sleep and breathing in subjects with mild-to-moderate OSA. Twenty-one male volunteers, who snored habitually, underwent polysomnography with and without 0.5 g alcohol x kg body weight (BW)(-1) consumed 90 min prior to sleep time, in random order. The mean blood alcohol concentration (BAC) following alcohol at the time of lights out was 0.07 g x dL(-1). The distribution amongst the various sleep stages was not significantly altered by alcohol. The mean apnoea/hypopnoea index rose from 7.1+/-1.9 to 9.7+/-2.1 events x h(-1) (mean+/-SEM, p=0.017); however, there was no significant change in the minimum arterial oxygen saturation measured by pulse oximetry Sp,O2, apnoea length or snoring intensity. Mean sleep cardiac frequency rose significantly from 53.9+/-1.4 to 59.9+/-1.9 beats x min(-1) (P<0.001) and overnight urinary noradrenalin increased from 14.9+/-2.3 to 18.8+/-2.3 nmol x mmol creatinine(-1) (p=0.061) on the alcohol night compared to the nonalcohol night. To conclude, modest alcohol consumption, giving a mean blood alcohol concentration of 0.07 g x dL(-1), significantly increases both obstructive sleep apnoea frequency and mean sleep cardiac frequency.

Acute Effects of Continuous Positive Airway Pressure on Cardiac Sympathetic Tone in Congestive Heart Failure

Background—Depressed ventricular performance and neurohormonal activation are key pathophysiological features of congestive heart failure (CHF). Although angiotensin-converting enzyme inhibitors and &bgr;-adrenoceptor blockers exert beneficial effects in CHF, mortality remains unacceptably high, and the development of further therapeutic approaches is warranted. Recent data suggest that continuous positive airway pressure (CPAP) may be of benefit in the treatment of CHF, although the mechanism for this action is incompletely understood. Methods and Results—In the present study, we examined the effect of short-term CPAP (10 cm H2O for 10 minutes) on hemodynamics (Swan Ganz catheter) and total systemic and cardiac sympathetic activity (norepinephrine spillover method) in 14 CHF patients in New York Heart Association class III. The application of CPAP was associated with a fall in cardiac output (4.8±0.3 to 4.4±0.2 L/min;P <0.05) and a significant reduction in cardiac norepinephrine spillover (370±58 to 299±55 pmol/min;P <0.05), although total systemic norepinephrine spillover was unchanged. Conclusion—The short-term application of CPAP results in an inhibition of cardiac sympathetic nervous activity. Further investigation into the potential value of long-term CPAP in CHF patients is warranted.