Bhavneesh Sharma

Adaptive Servoventilation for Treatment of Sleep-Disordered Breathing in Heart Failure: A Systematic Review and Meta-analysis

BACKGROUND Adaptive servoventilation (ASV) has demonstrated efficacy in treating sleep-disordered breathing (SDB) in patients with heart failure (HF), but large randomized trials are lacking. We, therefore, sought to perform a systematic review and meta-analysis of existing data. METHODS A systematic search of the PubMed database was undertaken in March 2012. Publications were independently assessed by two investigators to identify studies of ≥ 1-week duration that compared ASV to a control condition (ie, subtherapeutic ASV, continuous or bilevel pressure ventilation, oxygen therapy, or no treatment) in adult patients with SDB and HF. Mean, variability,and sample size data were extracted independently for the following outcomes: apneahypopnea index (AHI), left ventricular ejection fraction (LVEF), quality of life (SF-36 Health Survey; Medical Outcomes Trust), 6-min walk distance, peak oxygen consumption ( VO 2 ) % predicted, and ventilatory equivalent ratio for CO 2 ( VE / Vco 2 ) slope measured during exercise. Random effects meta-analysis models were applied. RESULTS Fourteen studies were identified (N = 538). Comparing ASV to control conditions, the weighted mean difference in AHI ( -14.64 events/h; 95% CI, -21.03 to - 8.25) and LVEF (0.40;95% CI, 0.08-0.71) both significantly favored ASV. ASV also improved the 6-min walk distance,but not peak O 2 % predicted, VE / VCO 2 slope, or quality of life, compared with control conditions. CONCLUSIONS In patients with HF and SDB, ASV was more effective than control conditions in reducing the AHI and improving cardiac function and exercise capacity. These data provide a compelling rationale for large-scale randomized controlled trials to assess the clinical impact of ASV on hard outcomes in these patients.

Sleep in Congestive Heart Failure

Breathing disorders during sleep are common in congestive heart failure (CHF). Sleep-disordered breathing (SDB) in CHF can be broadly classified as 2 types: central sleep apnea with Cheyne-Stokes breathing, and obstructive sleep apnea. Prevalence of SDB ranges from 47% to 76% in systolic CHF. Treatment of SDB in CHF may include optimization of CHF treatment, positive airway pressure therapy, and other measures such as theophylline, acetazolamide, and cardiac resynchronization therapy. Periodic limb movements are also common in CHF.

Evaluation of Right Ventricular Remodeling Using Cardiac Magnetic Resonance Imaging in Co-Existent Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea

Abstract Untreated chronic obstructive pulmonary disease (COPD) co-existing with obstructive sleep apnea (OSA), also known as overlap syndrome, has higher cardiovascular mortality than COPD alone but its underlying mechanism remains unclear. We hypothesize that the presence of overlap syndrome is associated with more extensive right ventricular (RV) remodeling compared to patients with COPD alone. Adult COPD patients (GOLD stage 2 or higher) with at least 10 pack-years of smoking history were included. Overnight laboratory-based polysomnography was performed to test for OSA. Subjects with an apnea-hypopnea index (AHI) >10/h were classified as having overlap syndrome (n = 7), else classified as having COPD-only (n = 11). A cardiac MRI was performed to assess right and left cardiac chambers sizes, ventricular masses, and cine function. RV mass index (RVMI) was markedly higher in the overlap group than the COPD-only group (19 ± 6 versus 11 ± 6; p = 0.02). Overlap syndrome subjects had a reduced RV remodeling index (defined as the ratio between RVMI and RV end-diastolic volume index) compared to the COPD-only group (0.27 ± 0.06 versus 0.18 ± 0.08; p = 0.02). In the overlap syndrome subjects, the extent of RV remodeling was associated with severity of oxygen desaturation (R2 = 0.65, p = 0.03). Our pilot results suggest that untreated overlap syndrome may cause more extensive RV remodeling than COPD alone.

Sleep Disordered Breathing in Patients with Heart Failure: Pathophysiology and Management

Opinion statementSleep disordered breathing (SDB) is common in heart failure patients across the range of ejection fractions and is associated with adverse prognosis. Although effective pharmacologic and device-based treatment of heart failure may reduce the frequency or severity of SDB, heart failure treatment alone may not be adequate to restore normal breathing during sleep. Continuous positive airway pressure (CPAP) is the major treatment for SDB in heart failure, especially if obstructive rather than central sleep apnea (CSA) predominates. Adequate suppression of CSA by PAP is associated with a heart transplant-free survival benefit, although randomized trials are ongoing. Bilevel PAP (BPAP) may be as effective as CPAP in treating SDB and may be preferable over CPAP in patients who experience expiratory pressure discomfort. Adaptive (or auto) servo-ventilation (ASV), which adjusts the PAP depending on the patient’s airflow or tidal volume, may be useful in congestive heart failure patients if CPAP is ineffective. Other therapies that have been proposed for SDB in congestive heart failure include nocturnal oxygen, CO2 administration (by adding dead space), theophylline, and acetazolamide; most of which have not been systematically studied in outcome-based prospective randomized trials.

T1 Measurements for Detection of Expansion of the Myocardial Extracellular Volume in Chronic Obstructive Pulmonary Disease

BACKGROUND We aimed to assess whether chronic obstructive pulmonary disease (COPD) is associated with expansion of the myocardial extracellular volume (ECV) using T1 measurements. METHODS Adult COPD patients Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2 or higher and free of known cardiovascular disease were recruited. All study patients underwent measures of pulmonary function, 6-minute walk test, serum measures of inflammation, overnight polysomnography, and a contrast cardiac magnetic resonance study. RESULTS Eight patients with COPD were compared with 8 healthy control subjects. The mean predicted forced expiratory volume at 1 second of COPD subjects was 68%. Compared with control subjects, patients had normal left ventricular (LV) and right ventricular size, mass, and function. However, compared with control subjects, the LV remodelling index (median, 0.87; interquartile range [IQR], 0.71-1.14; vs median, 0.62; IQR, 0.60-0.77; P ¼ 0.03) and active left atrial emptying fraction was increased (median, 46; IQR, 41-49; vs median, 38; IQR, 33-43; P ¼ 0.005), and passive left atrial emptying fraction was reduced (median, 24; IQR, 20-30; vs median, 44; IQR, 31-51; P ¼ 0.007). The ECV was increased in patients with COPD (median, 0.32; IQR, 0.05; vs median, 0.27; IQR, 0.05; P = 0.001). The ECV showed a strong positive association with LV remodelling (r = 0.72; P = 0.04) and an inverse association with the 6-minute walk duration (r = -0.79; P = 0.02) and passive left atrial emptying fraction (r = -0.68; P = 0.003). CONCLUSIONS Expansion of the ECV, suggestive of diffuse myocardial fibrosis, is present in COPD and is associated with LV remodelling, and reduced left atrial function and exercise capacity.

Obstructive Sleep Apnea : The Elephant in the Cardiovascular Room

Despite considerable advances in the relatively young field of sleep research, the importance of obstructive sleep apnea (OSA) remains underappreciated. A vast body of evidence based on animal,1 human cross-sectional and longitudinal research,2 and interventional studies3 suggests that OSA is associated with significant cardiovascular risk factors. In addition, new therapeutic targets are needed in the cardiovascular arena given that improvements in outcomes have plateaued in many studies. Unfortunately, however, OSA remains the “elephant in the room” and often is ignored even in high-risk patients. A telling example comes from the diabetes field, with recent data indicating that 86% of obese patients with type 2 diabetes also experience clinically significant OSA,4 with < 5% of these patients receiving OSA treatment 1 year after both the patient and his or her primary physician have received the diagnosis.5 The reasons that OSA is often overlooked as a potentially reversible cardiovascular risk factor are complex but probably lie in the small but growing number of mechanistic studies in this area.6,7 The profile of OSA also would be lifted by the execution of large-scale, multicenter, randomized controlled trials of continuous positive airway pressure (CPAP) with hard cardiovascular outcomes, which is a current research focus. The design of such trials presents an ethical challenge: Reductions in daytime sleepiness and neurocognitive impairment are likely to result from administering CPAP to symptomatic patients with OSA, which promotes a reluctance to randomize hypersomnolent patients (at risk for car accidents) to a long-duration arm without active treatment. Restricting entry criteria to nonsleepy patients presents issues around CPAP adherence because such patients may not perceive symptomatic benefit, and there is some evidence that only very small reductions in BP result from CPAP in nonsleepy patients.8 Thus, a negative result in a large-scale randomized controlled trial of CPAP in asymptomatic patients with OSA may simply mean that those who would demonstrate the greatest improvement were systematically excluded during recruitment. Thus, surrogate outcome measures that accurately predict fatal and nonfatal cardiovascular events are critical, allowing for shorter trial durations and, therefore, a reduced ethical dilemma. In this issue of CHEST (see page 674), Colish et al9 present new evidence that CPAP treatment is associated with a reduction in right atrial and ventricular size as well as a reduction in left ventricular mass as demonstrated by both transthoracic echocardiography and cardiac MRI (CMR), with no concurrent changes evident in a range of cardiac biomarkers that were within normal ranges at baseline. Strengths of the study include the multiple follow-up visits (3, 6, and 12 months after the initiation of CPAP) and the targeting of patients with a high Epworth Sleepiness Scale score at baseline. Such studies are crucial in defining the time period needed to see important cardiovascular morphologic and physiologic changes resulting from CPAP therapy in OSA. These data are critical to the design of future randomized protocols. Further, this study likely will have a substantial impact on clinicians and researchers outside the sleep field who are perhaps more likely to appreciate CMR outcome measures over polysomnography-derived outcomes, such as the apnea-hypopnea index. Left ventricular mass has been shown to predict future cardiac events10 and decreased survival in patients with heart failure.11 By demonstrating left ventricular remodeling with CPAP in an OSA sample, Colish et al9 have helped to fill this research gap. Despite the obvious strengths of the study, it has some limitations. The lack of a control group does not allow the beneficial cardiac remodeling to be attributed to CPAP; the natural history of CMR measurements among the OSA population is unknown, and therefore, it is possible that some degree of changes may have occurred without the addition of CPAP. As in all uncontrolled studies, diet, exercise, changes in medications, and medication adherence could have been affected by close monitoring and, thus, could have affected the outcomes. CPAP adherence in this study was high, and the fact that patients who are willing and able to enroll in a research study and are adherent to CPAP also may be more likely to embrace positive lifestyle changes should not be overlooked.12 However, this “healthy user” effect also can complicate randomized controlled trials if imbalances occur in the two arms after randomization. As with most novel research, the study by Colish et al9 has generated several questions for clinicians and scientists in the field. For the clinician, is CMR a useful clinical tool to monitor cardiovascular improvements, and will this approach help to improve CPAP adherence? Can pretreatment CMR act as a reliable marker for identifying patients at high cardiovascular risk, even possibly those with mild OSA, such that they can be rapidly provided with CPAP and comprehensive pharmacotherapy alongside intensive support to optimize adherence? Does the high cost of CMR outweigh these benefits in an era of health-care reform? For the scientist, what are the early pathologic and physiologic changes in the heart due to OSA, and what is the chronologic sequence and reversibility of these changes? Are there other surrogate cardiac imaging markers that could be used to detect adverse ventricular remodeling, even when chamber volumes, mass, and function appear normal? What duration of CPAP and level of adherence are required to see important changes in CMR? Can other OSA treatments, such as oral appliances, surgery, or alternative pressure modes, cause improvements in cardiac morphology and physiology similar to those seen with CPAP? Finally, if future studies are able to attribute irrefutably improvements seen with CMR to CPAP, are these changes predictive of hard cardiovascular end points such as myocardial infarction and stroke in OSA? Clearly, much work remains in answering these questions and elucidating the mechanistic link between OSA and cardiovascular disease, with studies such as that by Colish et al9 paving the way for this future research. We applaud the authors for moving us one step closer to the widespread appreciation of OSA.