Canadian Journal of Cardiology 31 (2015) 1202e1203
Journal News and Commentary
Increased Mortality Associated With Adaptive Servo-Ventilation Therapy in Heart Failure Patients With Central Sleep Apnea in the Halted SERVE-HF Trial Haran Yogasundaram, BSc, and Gavin Y. Oudit, MD, PhD Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
Heart failure (HF) is a complex syndrome that is increasing in prevalence on a worldwide basis and carries a high morbidity and mortality resulting in a huge economic burden. Although HF is initially driven by primary cardiac dysfunction, the syndrome culminates into a multisystem process involving the central nervous system, lungs, kidneys, and skeletal muscles. Targeting the involvement of noncardiac pathways remains an important approach to minimize the progression of HF and to improve clinical outcomes. As highlighted in the July 2015 issue of the Canadian Journal of Cardiology, sleep disordered breathing is strongly associated with HF, and treatment of central sleep apnea (CSA) and obstructive sleep apnea plays an important role in the management of these patients.1 Adaptive servo-ventilation (ASV) is a relatively new modality of noninvasive ventilation in which bilevel pressure support is provided coupled with additional inspiratory pressure support when an apneic event is detected.2 Short-term clinical studies using ASV in HF patients with sleep disordered breathing has shown an improvement in the apneahypopnea index (AHI), left ventricular ejection fraction (LVEF), quality of life, and the 6-minute walk distance.2 Two large multicentre randomized trials were initiated to assess the effect of ASV on long-term clinical outcomes in HF patients with sleep apnea: the Effect of Adaptive Servo Ventilation on Survival and Hospital Admissions in Heart Failure (ADVENT-HF) trial, which includes patients with obstructive sleep apnea and CSA, and the Adaptive Servo Ventilation in Patients With Heart Failure (SERVE-HF) trial, which involves HF patients with CSA only.1 The SERVE-HF trial enrolled patients with symptomatic HF (New York Heart Association II-IV), LVEF 45% and moderate and/or severe CSA (AHI > 15, central AHI/AHI > 50%, and central apnea
Received for publication July 22, 2015. Accepted July 22, 2015. Corresponding author: Dr Gavin Y. Oudit, Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. Tel.: þ1-780-407-8569; fax: þ1-780-407-6452. E-mail: [email protected] See page 1203 for disclosure information.
index > 10). On the basis of the early results of the SERVE-HF trial, there was a 33.5% increased relative risk of cardiovascular death compared with control patients who were not receiving ASV therapy (absolute annual risk: 10% in ASV patients vs 7.5% in control participants). ResMed Ltd has issued a safety advisory and recall for use of ASV mode in patients with HF and CSA, and in these patients ASV is now contraindicated.3 The unexpected increase in cardiovascular death occurring out of hospital in patients who received ASV highlights potential increased risk leading to sudden cardiac death. The use of an implantable cardioverter defibrillator (ICD) would have likely modified this risk and also provided an opportunity to capture and treat ventricular arrhythmias. The detailed results surrounding the unexpected death of patients in the SERVE-HF trial will be important including the interrogation of their ICDs. Likewise, in current patient survivors who have an ICD, device interrogation would provide further insight into a potential risk associated with ASV. Importantly, the use of ASV in the ongoing ADVENT-HF clinical trial and patients’ clinical status must be carefully monitored. The treatment of CSA is further complicated by the conflicting reports on the effect of CSA on mortality in HF patients1 and the argument that CSA carries a certain adaptive value in patients with advanced HF by optimizing V/Q matching, leading to energy conservation.4 Moreover, CSA and OSA are associated with disparate effects on hemodynamics in HF patients with the former leading to an increase in stroke volume and the latter leading to a reduction in stroke volume. The Canadian Continuous Positive Airway Pressure for Patients With Central Sleep Apnea and Heart Failure (CANPAP) trial, which used continuous positive airway pressure in HF patients, improved CSA, increased walking distance, and LVEF without increasing overall mortality.5 Therefore, HF patients with CSA who are optimally treated medically and with device therapy but remain symptomatic should be given a trial of continuous positive airway pressure therapy without ASV. The results of the SERVE-HF trial remind us that therapies that lead to short-term improvement in symptoms might not translate into durable and effective therapies. Notably, suppression of premature ventricular
http://dx.doi.org/10.1016/j.cjca.2015.07.712 0828-282X/Ó 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Yogasundaram and Oudit ASV Therapy Increased Mortality in SERVE-HF Trial
contractions (and palpitations) using type Ic antiarrhythmic agents increased mortality in patients with ischemic heart disease, and use of intravenous inotropes in HF patients relieved symptoms but increased mortality. Conversely, initiation of b-blockers often worsens symptoms subacutely only to lead to sustainable reduction in long-term morbidity and mortality.
Funding Sources Our research is supported by the Heart and Stroke Foundation, Canadian Institutes of Health Research, and Alberta Innovates-Health Solutions.
Disclosures The authors have no conflicts of interest to disclose.
1203
References 1. Lyons OD, Bradley TD. Heart failure and sleep apnea. Can J Cardiol 2015;31:898-908. 2. Sharma BK, Bakker JP, McSharry DG, et al. Adaptive servoventilation for treatment of sleep-disordered breathing in heart failure: a systematic review and meta-analysis. Chest 2012;142:1211-21. 3. Specific ResMed ventilators with adaptive ServoVentilation (ASV) increased risk of cardiovascular death in patients who have a specific heart condition. Available at: https://www.gov.uk/drug-device-alerts/specificresmed-ventilators-with-adaptive-servoventilation-asv-increased-risk-ofcardiovascular-death-in-patients-who-have-a-specific-heart-condition. Accessed June 12, 2015. 4. Naughton MT. Cheyne-stokes respiration: Friend or foe? Thorax 2012;67:357-60. 5. Bradley TD, Logan AG, Kimoff RJ, et al. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med 2005;353: 2025-33.
Journal News and Commentary
Increased Mortality Associated With Adaptive Servo-Ventilation Therapy in Heart Failure Patients With Central Sleep Apnea in the Halted SERVE-HF Trial Haran Yogasundaram, BSc, and Gavin Y. Oudit, MD, PhD Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
Heart failure (HF) is a complex syndrome that is increasing in prevalence on a worldwide basis and carries a high morbidity and mortality resulting in a huge economic burden. Although HF is initially driven by primary cardiac dysfunction, the syndrome culminates into a multisystem process involving the central nervous system, lungs, kidneys, and skeletal muscles. Targeting the involvement of noncardiac pathways remains an important approach to minimize the progression of HF and to improve clinical outcomes. As highlighted in the July 2015 issue of the Canadian Journal of Cardiology, sleep disordered breathing is strongly associated with HF, and treatment of central sleep apnea (CSA) and obstructive sleep apnea plays an important role in the management of these patients.1 Adaptive servo-ventilation (ASV) is a relatively new modality of noninvasive ventilation in which bilevel pressure support is provided coupled with additional inspiratory pressure support when an apneic event is detected.2 Short-term clinical studies using ASV in HF patients with sleep disordered breathing has shown an improvement in the apneahypopnea index (AHI), left ventricular ejection fraction (LVEF), quality of life, and the 6-minute walk distance.2 Two large multicentre randomized trials were initiated to assess the effect of ASV on long-term clinical outcomes in HF patients with sleep apnea: the Effect of Adaptive Servo Ventilation on Survival and Hospital Admissions in Heart Failure (ADVENT-HF) trial, which includes patients with obstructive sleep apnea and CSA, and the Adaptive Servo Ventilation in Patients With Heart Failure (SERVE-HF) trial, which involves HF patients with CSA only.1 The SERVE-HF trial enrolled patients with symptomatic HF (New York Heart Association II-IV), LVEF 45% and moderate and/or severe CSA (AHI > 15, central AHI/AHI > 50%, and central apnea
Received for publication July 22, 2015. Accepted July 22, 2015. Corresponding author: Dr Gavin Y. Oudit, Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. Tel.: þ1-780-407-8569; fax: þ1-780-407-6452. E-mail: [email protected] See page 1203 for disclosure information.
index > 10). On the basis of the early results of the SERVE-HF trial, there was a 33.5% increased relative risk of cardiovascular death compared with control patients who were not receiving ASV therapy (absolute annual risk: 10% in ASV patients vs 7.5% in control participants). ResMed Ltd has issued a safety advisory and recall for use of ASV mode in patients with HF and CSA, and in these patients ASV is now contraindicated.3 The unexpected increase in cardiovascular death occurring out of hospital in patients who received ASV highlights potential increased risk leading to sudden cardiac death. The use of an implantable cardioverter defibrillator (ICD) would have likely modified this risk and also provided an opportunity to capture and treat ventricular arrhythmias. The detailed results surrounding the unexpected death of patients in the SERVE-HF trial will be important including the interrogation of their ICDs. Likewise, in current patient survivors who have an ICD, device interrogation would provide further insight into a potential risk associated with ASV. Importantly, the use of ASV in the ongoing ADVENT-HF clinical trial and patients’ clinical status must be carefully monitored. The treatment of CSA is further complicated by the conflicting reports on the effect of CSA on mortality in HF patients1 and the argument that CSA carries a certain adaptive value in patients with advanced HF by optimizing V/Q matching, leading to energy conservation.4 Moreover, CSA and OSA are associated with disparate effects on hemodynamics in HF patients with the former leading to an increase in stroke volume and the latter leading to a reduction in stroke volume. The Canadian Continuous Positive Airway Pressure for Patients With Central Sleep Apnea and Heart Failure (CANPAP) trial, which used continuous positive airway pressure in HF patients, improved CSA, increased walking distance, and LVEF without increasing overall mortality.5 Therefore, HF patients with CSA who are optimally treated medically and with device therapy but remain symptomatic should be given a trial of continuous positive airway pressure therapy without ASV. The results of the SERVE-HF trial remind us that therapies that lead to short-term improvement in symptoms might not translate into durable and effective therapies. Notably, suppression of premature ventricular
http://dx.doi.org/10.1016/j.cjca.2015.07.712 0828-282X/Ó 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Yogasundaram and Oudit ASV Therapy Increased Mortality in SERVE-HF Trial
contractions (and palpitations) using type Ic antiarrhythmic agents increased mortality in patients with ischemic heart disease, and use of intravenous inotropes in HF patients relieved symptoms but increased mortality. Conversely, initiation of b-blockers often worsens symptoms subacutely only to lead to sustainable reduction in long-term morbidity and mortality.
Funding Sources Our research is supported by the Heart and Stroke Foundation, Canadian Institutes of Health Research, and Alberta Innovates-Health Solutions.
Disclosures The authors have no conflicts of interest to disclose.
1203
References 1. Lyons OD, Bradley TD. Heart failure and sleep apnea. Can J Cardiol 2015;31:898-908. 2. Sharma BK, Bakker JP, McSharry DG, et al. Adaptive servoventilation for treatment of sleep-disordered breathing in heart failure: a systematic review and meta-analysis. Chest 2012;142:1211-21. 3. Specific ResMed ventilators with adaptive ServoVentilation (ASV) increased risk of cardiovascular death in patients who have a specific heart condition. Available at: https://www.gov.uk/drug-device-alerts/specificresmed-ventilators-with-adaptive-servoventilation-asv-increased-risk-ofcardiovascular-death-in-patients-who-have-a-specific-heart-condition. Accessed June 12, 2015. 4. Naughton MT. Cheyne-stokes respiration: Friend or foe? Thorax 2012;67:357-60. 5. Bradley TD, Logan AG, Kimoff RJ, et al. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med 2005;353: 2025-33.
