Effects of Short-Term Continuous Positive Airway Pressure on Myocardial Sympathetic Nerve Function and Energetics in Patients With Heart Failure and Obstructive Sleep Apnea

Abstract

O bstructive sleep apnea (OSA), present in approximately a third of all patients with heart failure (HF) with reduced ejection fraction (HFrEF), [1][2][3] is an independent predictor of mortality. 4 Common to both HFrEF and OSA are sympathetic nervous system (SNS) activation and impaired myocardial energetic efficiency. Clinical Perspective on p 901Myocardial efficiency estimates the capacity of the heart to convert oxygen into effective forward stroke work.5-9 The noninvasively derived cardiac work metabolic index (WMI) estimates efficiency by quantifying forward minute-work of the Background-Heart failure with reduced ejection fraction and obstructive sleep apnea (OSA), 2 states of increased metabolic demand and sympathetic nervous system activation, often coexist. Continuous positive airway pressure (CPAP), which alleviates OSA, can improve ventricular function. It is unknown whether this is due to altered oxidative metabolism or presynaptic sympathetic nerve function. We hypothesized that short-term (6-8 weeks) CPAP in patients with OSA and heart failure with reduced ejection fraction would improve myocardial sympathetic nerve function and energetics. Methods and Results-Forty-five patients with OSA and heart failure with reduced ejection fraction (left ventricular ejection fraction 35.8±9.7% [mean±SD]) were evaluated with the use of echocardiography and 11 C-acetate and 11 C-hydroxyephedrine positron emission tomography before and ≈6 to 8 weeks after randomization to receive short-term CPAP (n=22) or no CPAP (n=23). Work metabolic index, an estimate of myocardial efficiency, was calculated as follows: (stroke volume index×heart rate×systolic blood pressure÷K mono ), where K mono is the monoexponential function fit to the myocardial ; P=0.003). There was no significant change in work metabolic index between groups. However, in those with more severe OSA (apnea-hypopnea index >20 events per hour), CPAP significantly increased both work metabolic index and systolic blood pressure (P<0.05). Conclusions-In patients with heart failure with reduced ejection fraction and OSA, short-term CPAP increased hydroxyephedrine retention, indicating improved myocardial sympathetic nerve function, but overall did not affect energetics. In those with more severe OSA, CPAP may improve cardiac efficiency. Further outcome-based investigation of the consequences of CPAP is warranted. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00756366.(Circulation. 2014;130:892-901.)

Tight software, methodological/physiological variation, less so

“…The ability to measure MBFrst and MVO2 with a single tracer injection makes the PET 11 C-acetate a very attractive one. 1,[3][4][5][6] List mode data acquisition also makes possible measurement of LV end diastolic and systolic volumes as well as LV mass and hence MEE. 7 Thus, parenthetically, any variation in test-retest repeatability related to non-simultaneous acquisition of PET and echo data alluded to by the authors potentially could have been mitigated had list mode acquisition of the PET data been obtained.…”

“…The patients were all studied at the authors' institution (Ottawa Heart Institute; OHI) as part of a larger study of patients with HFrEF and obstructive sleep apnea (OSA) though patients in the current study did not have OSA and their data were not included in the earlier report. 1 Instead, the data were retrospectively analyzed to determine intra-and interobserver repeatability and reproducibility of PET 11 Cacetate measurements of MBFrst and MVO2 and derived indices, MEE and WMI. Repeatability of all the measurements was assessed on average * 1.5 months post baseline, without overt change in patients' clinical condition.…”

Sleep-Disordered Breathing in Heart Failure ― A Therapeutic Dilemma ―

“…55, 56 In a more recent trial evaluating myocardial sympathetic nerve function and cardiac energetics, 6-8 weeks of CPAP treatment increased cardiac retention of 11 C-hydroxyephredrine, a norepinephrine (NE) analog and marker of myocardial sympathetic nerve function; in those with the most severe OSA, CPAP also improved cardiac efficiency. 57 Concurrently, investigations and trials involving nonsleepy subjects with OSA (and in one trial with coexisting coronary artery disease) but without HF detected no overall treatment effect on daytime alertness, QOL, neurocognitive function, BP, cardiovascular morbidity, or life expectancy. 58-61 These observations, plus the demonstration that HFrEF patients with SDB are for the most part not hyper-somnolent, 1,2 alleviated the sleep medicine community's concerns and enabled large randomized trials evaluating the effect of treating OSA on mortality and cardiovascular events.…”

Atrial arrhythmogenesis in obstructive sleep apnea: Therapeutic implications

“…In patients with heart failure and OSA, short-term CPAP improved myocardial sympathetic nerve function, but overall did not affect energetics suggesting improved cardiac efficiency [67]. Different studies provided evidence that continuous positive airway pressure (CPAP) therapy in OSA reduces 24 h urinary catecholamine excretion as well as plasma norepinephrine levels, consistent with a reduction in sympathetic nerve activity [68,69].…”