Catheterization and Cardiovascular Interventions 84:1146–1147 (2014)
Editorial Comment Sleep Apnea and Stroke: Lifting the Veil of Cardiac Hemodynamics During Sleep Pranav M. Patel,1* MD, FSCAI, and Morton J. Kern,1,2 MD, FSCAI 1 Division of Cardiology, Department of Medicine, University of California, Irvine, Orange, California 2 Department of Medicine, Veterans Administration Health Care System, Long Beach, California
Sleep repairs our body, rests our mind, and results in both psychological and physiological healing. Even in Macbeth, Shakespeare describes “sleep that knits up the unraveled sleeve of care, the death of each day’s life, sore labor’s bath, balm of hurt minds, great nature’s second course, Chief nourisher in life’s feast.” Such affirmative traits, however, are often lost in obstructive sleep apnea (OSA) where sleep (and the associated apnea) can be linked to adverse cardiovascular and cerebrovascular events [1]. Disturbed pathologic sleep with apnea is common. Studies estimate that up to 17% of the adult population has OSA with an increased prevalence in patients over 65 years [1,2]. OSA is associated with diabetes, obesity, hypertension, and is an independent predictor for ischemic stroke. [1,2]. Risk for cardioembolism is increased with OSA especially in those patients with patent foramen ovale (PFO) as well as cardiacrhythm disorders [2]. It has also been suggested that patients with OSA have an increased risk of paradoxical emboli [3] because of the increased intrathoracic pressure and hence increased right atrial (RA) pressure during the apneic period. Although, very plausible, this postulated increase in apneic pressure has never been directly measured or verified. In this issue of Catheterization and Cardiovascular Interventions, Konecny et al. [4] hypothesized that simulated OSA (via the Mueller maneuver (MM) of inspiration against a closed glottis) in a conscious subject would increase the intra-atrial right-to-left pressure gradient, thus providing the suitable substrate for right-toleft atrial shunting and supporting a mechanism for increased strokes in the OSA patient. In 10 patients, directly measured inter-atrial pressures and gradient during simulated OSA and at rest were obtained using C 2014 Wiley Periodicals, Inc. V
high-fidelity micromanometer catheters. The authors found that during the onset of MM, RA pressure transiently but consistently exceeded left atrial (LA) pressure (maximum RA-LA pressure gradient increased from 0.1 6 1.4 mm Hg at baseline to 7.0 6 4.3 mm Hg during MM, P < 0.001). Additionally, the maximum rightto-left atrial pressure gradient during MM was higher than that achieved during Valsalva maneuver release (P < 0.007). These findings explain the hemodynamic changes of potential right to left shunting during OSA, and implicate important intracardiac hemodynamics changes occurring during aberrant sleep. There are various mechanisms that contribute the increased risk of stroke in OSA [5]. Konecny and colleagues [4] should be commended on investigating one mechanism producing cardioembolic events via a PFO. In the setting of transiently elevated RA pressure (compared to LA pressure) were more marked during apnea than during Valsalva maneuvers. The cardiac hemodynamics could be further corroborated by simultaneous two-dimensional echo bubble studies demonstrating the paradoxical movement of echo contrast that would explain an OSA stroke. There are several limitations to their small study [4]. It is unknown whether the use of a simulated OSA with the Muller maneuver would underestimate the pressure differences compared to actual OSA. Likewise the degree to which a catheter through the PFO would artificially increase the PFO patency is incompletely appreciated. Nonetheless, the detailed hemodynamic study of Konecny et al. [4] adds to our knowledge of the possible pathophysiologic mechanism of ischemic cardioembolic cerebrovascular accident (CVA) in OSA. The current investigation encourages future studies of intracardiac hemodynamic changes in relationship to the timing of PFO opening that has potential Conflict of interest: Nothing to report. *Correspondence to: Pranav M. Patel, MD, FSCAI; Division of Cardiology, University of California, Irvine, 333 City Drive West City Tower, Suite 400, Orange, CA 92868-4080. E-mail: pranavp@ uci.edu Received 6 October 2014; Revision accepted 7 October 2014 DOI: 10.1002/ccd.25693 Published online 19 November 2014 in Wiley Online Library (wileyonlinelibrary.com)
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importance in OSA patients who are treated with continuous positive airway pressure therapy. Pressure measurements alone will not be sufficient to dissect the complete story. Research collaborations among the different medical specialties involved with the OSA patient will ultimately improve our knowledge, prevention, and clinical outcomes. As anticipated advances occur, we may further “lift the veil” and improve our knowledge of the cardiovascular hemodynamics involved in sleep disorders.
2.
3.
4.
REFERENCES 1. Somers VK, White DP, Amin R, et al. Sleep apnea and cardiovascular disease: An American Heart Association/American College Of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical
5.
Cardiology, Stroke Council, and Council On Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation 2008;118:1080–1111. Nieto FJ, Young TB, Lind BK, et al. Association of sleepdisordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep heart health study. JAMA 2000; 283:1829–1836. Lau EM, Yee BJ, Grunstein RR, Celermajer DS. Patent foramen ovale and obstructive sleep apnea: A new association? Sleep Med Rev 2010;14:391–395. Konecny T, Khanna A, Novak J, Jama A, Zawadowski GM, Orban M, Pressman G, Bukartyk J, Kara T, Cetta F, Borlaug BA, Somers VK, Reeder GS. Inter-atrial pressure gradients during simulated obstructive sleep apnea: A catheter-based study. Catheter Cardiovasc Interv, in press. Wessendorf TE, Thilman AF, Wang YM, Schreiber A, Konietzko N, Teschler H. Fibrinogen levels and obstructive sleep apnea in ischemic stroke. Am J Respir Crit Care Med 2000;162:2039– 2042.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
Editorial Comment Sleep Apnea and Stroke: Lifting the Veil of Cardiac Hemodynamics During Sleep Pranav M. Patel,1* MD, FSCAI, and Morton J. Kern,1,2 MD, FSCAI 1 Division of Cardiology, Department of Medicine, University of California, Irvine, Orange, California 2 Department of Medicine, Veterans Administration Health Care System, Long Beach, California
Sleep repairs our body, rests our mind, and results in both psychological and physiological healing. Even in Macbeth, Shakespeare describes “sleep that knits up the unraveled sleeve of care, the death of each day’s life, sore labor’s bath, balm of hurt minds, great nature’s second course, Chief nourisher in life’s feast.” Such affirmative traits, however, are often lost in obstructive sleep apnea (OSA) where sleep (and the associated apnea) can be linked to adverse cardiovascular and cerebrovascular events [1]. Disturbed pathologic sleep with apnea is common. Studies estimate that up to 17% of the adult population has OSA with an increased prevalence in patients over 65 years [1,2]. OSA is associated with diabetes, obesity, hypertension, and is an independent predictor for ischemic stroke. [1,2]. Risk for cardioembolism is increased with OSA especially in those patients with patent foramen ovale (PFO) as well as cardiacrhythm disorders [2]. It has also been suggested that patients with OSA have an increased risk of paradoxical emboli [3] because of the increased intrathoracic pressure and hence increased right atrial (RA) pressure during the apneic period. Although, very plausible, this postulated increase in apneic pressure has never been directly measured or verified. In this issue of Catheterization and Cardiovascular Interventions, Konecny et al. [4] hypothesized that simulated OSA (via the Mueller maneuver (MM) of inspiration against a closed glottis) in a conscious subject would increase the intra-atrial right-to-left pressure gradient, thus providing the suitable substrate for right-toleft atrial shunting and supporting a mechanism for increased strokes in the OSA patient. In 10 patients, directly measured inter-atrial pressures and gradient during simulated OSA and at rest were obtained using C 2014 Wiley Periodicals, Inc. V
high-fidelity micromanometer catheters. The authors found that during the onset of MM, RA pressure transiently but consistently exceeded left atrial (LA) pressure (maximum RA-LA pressure gradient increased from 0.1 6 1.4 mm Hg at baseline to 7.0 6 4.3 mm Hg during MM, P < 0.001). Additionally, the maximum rightto-left atrial pressure gradient during MM was higher than that achieved during Valsalva maneuver release (P < 0.007). These findings explain the hemodynamic changes of potential right to left shunting during OSA, and implicate important intracardiac hemodynamics changes occurring during aberrant sleep. There are various mechanisms that contribute the increased risk of stroke in OSA [5]. Konecny and colleagues [4] should be commended on investigating one mechanism producing cardioembolic events via a PFO. In the setting of transiently elevated RA pressure (compared to LA pressure) were more marked during apnea than during Valsalva maneuvers. The cardiac hemodynamics could be further corroborated by simultaneous two-dimensional echo bubble studies demonstrating the paradoxical movement of echo contrast that would explain an OSA stroke. There are several limitations to their small study [4]. It is unknown whether the use of a simulated OSA with the Muller maneuver would underestimate the pressure differences compared to actual OSA. Likewise the degree to which a catheter through the PFO would artificially increase the PFO patency is incompletely appreciated. Nonetheless, the detailed hemodynamic study of Konecny et al. [4] adds to our knowledge of the possible pathophysiologic mechanism of ischemic cardioembolic cerebrovascular accident (CVA) in OSA. The current investigation encourages future studies of intracardiac hemodynamic changes in relationship to the timing of PFO opening that has potential Conflict of interest: Nothing to report. *Correspondence to: Pranav M. Patel, MD, FSCAI; Division of Cardiology, University of California, Irvine, 333 City Drive West City Tower, Suite 400, Orange, CA 92868-4080. E-mail: pranavp@ uci.edu Received 6 October 2014; Revision accepted 7 October 2014 DOI: 10.1002/ccd.25693 Published online 19 November 2014 in Wiley Online Library (wileyonlinelibrary.com)
1147
importance in OSA patients who are treated with continuous positive airway pressure therapy. Pressure measurements alone will not be sufficient to dissect the complete story. Research collaborations among the different medical specialties involved with the OSA patient will ultimately improve our knowledge, prevention, and clinical outcomes. As anticipated advances occur, we may further “lift the veil” and improve our knowledge of the cardiovascular hemodynamics involved in sleep disorders.
2.
3.
4.
REFERENCES 1. Somers VK, White DP, Amin R, et al. Sleep apnea and cardiovascular disease: An American Heart Association/American College Of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical
5.
Cardiology, Stroke Council, and Council On Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation 2008;118:1080–1111. Nieto FJ, Young TB, Lind BK, et al. Association of sleepdisordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep heart health study. JAMA 2000; 283:1829–1836. Lau EM, Yee BJ, Grunstein RR, Celermajer DS. Patent foramen ovale and obstructive sleep apnea: A new association? Sleep Med Rev 2010;14:391–395. Konecny T, Khanna A, Novak J, Jama A, Zawadowski GM, Orban M, Pressman G, Bukartyk J, Kara T, Cetta F, Borlaug BA, Somers VK, Reeder GS. Inter-atrial pressure gradients during simulated obstructive sleep apnea: A catheter-based study. Catheter Cardiovasc Interv, in press. Wessendorf TE, Thilman AF, Wang YM, Schreiber A, Konietzko N, Teschler H. Fibrinogen levels and obstructive sleep apnea in ischemic stroke. Am J Respir Crit Care Med 2000;162:2039– 2042.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
