- Email: [email protected]
CPAP in Obstructive Sleep Apnea and Atrial Flutter-Fibrillation: Response
Ivan F. N. Hung, MD Kwok-Yung Yuen, MD Hong Kong, China Affiliations: From the Department of Medicine (Dr Hung) and the Department of Microbiology (Dr Yuen), University of Hong Kong. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Kwok-Yung Yuen, MD, Department of Microbiology, University of Hong Kong, Room 423, Pathology Bldg, Queen Mary Hospital Compound, 102 Pokfulam Rd, Hong Kong, China; e-mail: [email protected] © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-0571
References 1. Hung IFN, To KKW, Lee C-K, et al. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest. 2013;144(2):464-473.
CPAP in Obstructive Sleep Apnea and Atrial Flutter-Fibrillation Is This Truly Two for the Price of One? To the Editor: There is growing research interest in the association between atrial fibrillation (AF) and obstructive sleep apnea (OSA), which are independently common diseases that have a serious impact on health, quality of life, and health-care resources.1 In many cases, both these diseases show a parallelism in that appropriate early diagnosis and treatment have demonstrated positive clinical benefits.1 However, studies are promoting positive interactions of CPAP for preventing and reducing recurrences of AF, despite the lack of clear evidence-based analysis and guidelines. We read with interest the article by Bazan et al2 in CHEST (May 2013) in this area of growing interest. We would like to comment on some aspects of their study that are relevant to clinical practice. First, there are some functional and structural cardiac changes that were not evaluated in this study and could potentially influence the results. The relationship between the duration of CPAP use and echocardiographic findings were not discussed but can provide a better understanding of whether CPAP could influence AF and recurrences. Additionally, echocardiographic factors such as left atrial diameter variations, severity of mitral valve regurgitation, and left ventricular hypertrophy were not measured,3 but these are potentially strong predictive factors for AF and recurrences. Second, the authors did not describe correlations between OSA, efficacy of antiarrhythmic drugs, and CPAP therapy and AF recurrence.4 Third, there were no data on CPAP compliance and duration of CPAP use among patients who had and did not have AF recurrences following ablation therapy for atrial flutter. Fourth, the authors presented no data on other causal factors for AF. In one study, OSA was a strong predictor of recurrent AF after an ablation procedure; BMI, ejection fraction, left atrial size, and hypertension did not affect the outcomes postablation for atrial flutter.5 Finally, other relevant measurements such as levels of N-terminal pro-B-type natriuretic peptide or B-type natriuretic peptide were not provided.
We believe that the study by Bazan et al2 provides valuable information with regard to OSA and AF recurrences, but mechanisms that influence this association remain complex. Further studies that look at cardiac structural and functional modifications to identify triggers or promoters of atrial flutter recurrences are necessary. Antonio M. Esquinas, MD, PhD, FCCP Murcia, Spain Egbert Pravinkumar, MD Houston, TX Affiliations: From the Intensive Care Unit (Dr Esquinas), Hospital General Universitario Morales Meseguer; and Department of Critical Care (Dr Pravinkumar), Division of Anesthesiology and Critical Care, The University of Texas MD Anderson Cancer Center. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Antonio M. Esquinas, MD, PhD, FCCP, Intensive Care Unit, Hospital General Universitario Morales Meseguer, Av Marques de los Velez, s/n, Murcia 30008, Spain; e-mail: [email protected] © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-0621
References 1. Digby GC, Baranchuk A. Sleep apnea and atrial fibrillation; 2012 update. Curr Cardiol Rev. 2012;8(4):265-272. 2. Bazan V, Grau N, Valles E, et al. Obstructive sleep apnea in patients with typical atrial flutter: prevalence and impact on arrhythmia control outcome. Chest. 2013;143(5):1277-1283. 3. Da Costa A, Romeyer C, Mourot S, et al. Factors associated with early atrial fibrillation after ablation of common atrial flutter. A single centre prospective study. Eur Heart J. 2002; 23(6):498-506. 4. Monahan K, Brewster J, Wang L, et al. Relation of the severity of obstructive sleep apnea in response to anti-arrhythmic drugs in patients with atrial fibrillation or atrial flutter. Am J Cardiol. 2012;110(3):369-372. 5. Jongnarangsin K, Chugh A, Good E, et al. Body mass index, obstructive sleep apnea, and outcomes of catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 2008;19(7): 668-672.
Response To the Editor: We sincerely appreciate the comments of Drs Esquinas and Pravinkumar regarding our article in CHEST1 on obstructive sleep apnea (OSA), atrial flutter (AF), and reduction of new-onset atrial fibrillation (AFib) by CPAP treatment. We hypothesized about a selective physiopathologic interaction between OSA and AF (as suggested by an 82% prevalence of OSA in patients with AF), in which pulmonary hypertension during apnea episodes or other mechanisms would induce right atrial overload and/or remodeling, thus favoring the occurrence of AF.2 We further theorized a beneficial impact of CPAP early in the atrial remodeling process leading to AFib (before any AFib documentation), independent or not of AF being documented.3 In our study, no serial echocardiography was performed to evaluate the structural changes induced by CPAP. Therefore, hemodynamic mechanisms through which CPAP presumably protects from AFib remain unclear.
journal.publications.chestnet.org
Downloaded From: http://journal.publications.chestnet.org/ by David Kinnison on 08/06/2013
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Only six patients without previous AFib were given antiarrhythmic drugs (AADs), and interaction between AADs and CPAP did not influence the incidence of AFib during follow-up among them (P 5 1) (our unpublished data, 2013). CPAP did not add any clinical benefit to AADs in patients with previous AFib documentation (P 5 .53, unpublished data). Compliance and duration of CPAP use was not higher in patients who did not have AFib during follow-up, and lack of “antiarrhythmic” efficacy of CPAP in patients with previous AFib cannot be attributed to a lower use of this therapy in this subgroup. A prior history of AFib is the strongest risk factor for recurrent AFib after AF ablation.4 It would appear by our results that other acknowledged variables (left atrial size, hypertension, ejection fraction, atrial stretching biomarkers, BMI, etc) are not as predictive. Again, this study was not designed to assess for risk factors of AFib, but to determine the impact of an intervention (CPAP) on a reduction of AFib after AF ablation (from 46% to 6% of cases, P 5 .025). We may conclude that documentation of AF sets for the identification of a subset of patients in whom underlying OSA is highly likely. This fact has notable implications in terms of cardiovascular morbidity and mortality.5 This also appears to include a lower incidence of AFib after CPAP initiation if this arrhythmia has never been documented.1 Further investigation will be needed to assess the etiopathogenic relationship between OSA and AF and the physiologic changes induced by CPAP that prevent AFib in some patients with AF. Victor Bazan, PhD Nuria Grau, MD Barcelona, Spain Affiliations: From the Electrophysiology Unit (Dr Bazan), Cardiology Department; and Sleep Disorders Unit (Dr Grau), Respiratory Medicine Department, Hospital del Mar, Parc de Salut Mar, Universitat Autònoma de Barcelona. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence: Victor Bazan, PhD, Hospital del Mar, Parc de Salut Mar, Universitat Autònoma de Barcelona, 25 Passeig Marítim, 08003 Barcelona, Spain; e-mail: [email protected] © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-0999
References 1. Bazan V, Grau N, Valles E, et al. Obstructive sleep apnea in patients with typical atrial flutter: prevalence and impact on arrhythmia control outcome. Chest. 2013;143(5):1277-1283. 2. Tongers J, Schwerdtfeger B, Klein G, et al. Incidence and clinical relevance of supraventricular tachyarrhythmias in pulmonary hypertension. Am Heart J. 2007;153(1):127-132. 3. Savelieva I, Kakouros N, Kourliouros A, Camm AJ. Upstream therapies for management of atrial fibrillation: review of clinical evidence and implications for European Society of Cardiology guidelines. Part I: primary prevention. Europace. 2011; 13(3):308-328. 4. Da Costa A, Romeyer C, Mourot S, et al. Factors associated with early atrial fibrillation after ablation of common atrial flutter. A single centre prospective study. Eur Heart J. 2002;23(6): 498-506. 5. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005;353(19):2034-2041.
N2 Nodal Involvement in Multiple Primary Lung Cancer Really an Exclusion Criterion? To the Editor: Girard et al1 reported in CHEST (January 2010) a comparison analysis of seven patients with multiple lung adenocarcinomas benchmarked on the epidermal growth factor receptor (EGFR) and Kirsten-rat sarcoma 2 viral oncogene homolog clonality status, which we read with interest and has instigated some reflections. Martini-Melamed (MM) criteria outlined a clinical and diagnostic classification of multiple primary lung cancers (MPLCs)2; today, American College of Chest Physicians (ACCP) guidelines provided a new MPLC classification.3 Both MM and ACCP criteria are used to classify an MPLC case as primary metastatic or true synchronous/metachronous multiple. Furthermore, none of these criteria incorporate information on molecular status to distinguish multiple primary from metastatic disease. The new diagnostic algorithm described by Takamochi and colleagues4 is based on the assessment of EGFR-Kirsten-rat sarcoma 2 viral oncogene homolog to achieve a correct definition of the clonality status among multiple lung adenocarcinomas and, in turn, is used as a differential diagnosis criterion. With this algorithm, Takamochi and colleagues4 could easily detect significant discrepancies in existing clinical criteria in 36 patients they thoroughly examined to assess the difference between true primary and metastatic disease. Similar evidence was reported in Girard et al,1 thus, confirming the inherent limitations of the MM/ACCP criteria. Moreover, Takuwa et al5 advocated for molecular-based stratification criteria by detailing a case of multiple synchronous lung adenocarcinomas harboring an L858R mutation within exon 21 of EGFR in the middle-lobe tumor and subcarinal nodes but not in the upperlobe tumor. In the setting where MM/ACCP criteria are taken into account, the diagnosis of N2 nodal involvement defines synchronous multiple tumors as metastatic lesions; however, these data might suggest that the number of multiple primary adenocarcinomas could be higher than what is observed if only MM/ACCP criteria are taken into account. On the other hand, very few reports compare the clonality status of primary tumors and lymph node metastases6: of 56 non-small cell lung cancers, the molecular appearance in the primary cancer and its lymph node metastasis were concordant in 92.9% and 69.6% by p53 and EGFR status, respectively. According to the high concordance between the clonality of primary tumors with metastatic spread to the lymph nodes, it could be suggested that, in the case of multiple adenocarcinomas, a clonality status evaluation in the mediastinal lymph node metastasis should also be performed. We would appreciate the authors’ opinion about whether the assessment of the clonal lymph node status of their series of seven patients would be a valuable piece of information.
714
Downloaded From: http://journal.publications.chestnet.org/ by David Kinnison on 08/06/2013
Giovanni Leuzzi, MD Alfredo Cesario, MD Marco Chiappetta, MD Stefano Margaritora, PhD Venanzio Porziella, MD Elisa Meacci, MD Maria L. Vita, MD Maria T. Congedo, MD Pierluigi Granone, PhD Rome, Italy
Correspondence
References 1. Hung IFN, To KKW, Lee C-K, et al. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest. 2013;144(2):464-473.
CPAP in Obstructive Sleep Apnea and Atrial Flutter-Fibrillation Is This Truly Two for the Price of One? To the Editor: There is growing research interest in the association between atrial fibrillation (AF) and obstructive sleep apnea (OSA), which are independently common diseases that have a serious impact on health, quality of life, and health-care resources.1 In many cases, both these diseases show a parallelism in that appropriate early diagnosis and treatment have demonstrated positive clinical benefits.1 However, studies are promoting positive interactions of CPAP for preventing and reducing recurrences of AF, despite the lack of clear evidence-based analysis and guidelines. We read with interest the article by Bazan et al2 in CHEST (May 2013) in this area of growing interest. We would like to comment on some aspects of their study that are relevant to clinical practice. First, there are some functional and structural cardiac changes that were not evaluated in this study and could potentially influence the results. The relationship between the duration of CPAP use and echocardiographic findings were not discussed but can provide a better understanding of whether CPAP could influence AF and recurrences. Additionally, echocardiographic factors such as left atrial diameter variations, severity of mitral valve regurgitation, and left ventricular hypertrophy were not measured,3 but these are potentially strong predictive factors for AF and recurrences. Second, the authors did not describe correlations between OSA, efficacy of antiarrhythmic drugs, and CPAP therapy and AF recurrence.4 Third, there were no data on CPAP compliance and duration of CPAP use among patients who had and did not have AF recurrences following ablation therapy for atrial flutter. Fourth, the authors presented no data on other causal factors for AF. In one study, OSA was a strong predictor of recurrent AF after an ablation procedure; BMI, ejection fraction, left atrial size, and hypertension did not affect the outcomes postablation for atrial flutter.5 Finally, other relevant measurements such as levels of N-terminal pro-B-type natriuretic peptide or B-type natriuretic peptide were not provided.
We believe that the study by Bazan et al2 provides valuable information with regard to OSA and AF recurrences, but mechanisms that influence this association remain complex. Further studies that look at cardiac structural and functional modifications to identify triggers or promoters of atrial flutter recurrences are necessary. Antonio M. Esquinas, MD, PhD, FCCP Murcia, Spain Egbert Pravinkumar, MD Houston, TX Affiliations: From the Intensive Care Unit (Dr Esquinas), Hospital General Universitario Morales Meseguer; and Department of Critical Care (Dr Pravinkumar), Division of Anesthesiology and Critical Care, The University of Texas MD Anderson Cancer Center. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Antonio M. Esquinas, MD, PhD, FCCP, Intensive Care Unit, Hospital General Universitario Morales Meseguer, Av Marques de los Velez, s/n, Murcia 30008, Spain; e-mail: [email protected] © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-0621
References 1. Digby GC, Baranchuk A. Sleep apnea and atrial fibrillation; 2012 update. Curr Cardiol Rev. 2012;8(4):265-272. 2. Bazan V, Grau N, Valles E, et al. Obstructive sleep apnea in patients with typical atrial flutter: prevalence and impact on arrhythmia control outcome. Chest. 2013;143(5):1277-1283. 3. Da Costa A, Romeyer C, Mourot S, et al. Factors associated with early atrial fibrillation after ablation of common atrial flutter. A single centre prospective study. Eur Heart J. 2002; 23(6):498-506. 4. Monahan K, Brewster J, Wang L, et al. Relation of the severity of obstructive sleep apnea in response to anti-arrhythmic drugs in patients with atrial fibrillation or atrial flutter. Am J Cardiol. 2012;110(3):369-372. 5. Jongnarangsin K, Chugh A, Good E, et al. Body mass index, obstructive sleep apnea, and outcomes of catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 2008;19(7): 668-672.
Response To the Editor: We sincerely appreciate the comments of Drs Esquinas and Pravinkumar regarding our article in CHEST1 on obstructive sleep apnea (OSA), atrial flutter (AF), and reduction of new-onset atrial fibrillation (AFib) by CPAP treatment. We hypothesized about a selective physiopathologic interaction between OSA and AF (as suggested by an 82% prevalence of OSA in patients with AF), in which pulmonary hypertension during apnea episodes or other mechanisms would induce right atrial overload and/or remodeling, thus favoring the occurrence of AF.2 We further theorized a beneficial impact of CPAP early in the atrial remodeling process leading to AFib (before any AFib documentation), independent or not of AF being documented.3 In our study, no serial echocardiography was performed to evaluate the structural changes induced by CPAP. Therefore, hemodynamic mechanisms through which CPAP presumably protects from AFib remain unclear.
journal.publications.chestnet.org
Downloaded From: http://journal.publications.chestnet.org/ by David Kinnison on 08/06/2013
CHEST / 144 / 2 / AUGUST 2013
713
Only six patients without previous AFib were given antiarrhythmic drugs (AADs), and interaction between AADs and CPAP did not influence the incidence of AFib during follow-up among them (P 5 1) (our unpublished data, 2013). CPAP did not add any clinical benefit to AADs in patients with previous AFib documentation (P 5 .53, unpublished data). Compliance and duration of CPAP use was not higher in patients who did not have AFib during follow-up, and lack of “antiarrhythmic” efficacy of CPAP in patients with previous AFib cannot be attributed to a lower use of this therapy in this subgroup. A prior history of AFib is the strongest risk factor for recurrent AFib after AF ablation.4 It would appear by our results that other acknowledged variables (left atrial size, hypertension, ejection fraction, atrial stretching biomarkers, BMI, etc) are not as predictive. Again, this study was not designed to assess for risk factors of AFib, but to determine the impact of an intervention (CPAP) on a reduction of AFib after AF ablation (from 46% to 6% of cases, P 5 .025). We may conclude that documentation of AF sets for the identification of a subset of patients in whom underlying OSA is highly likely. This fact has notable implications in terms of cardiovascular morbidity and mortality.5 This also appears to include a lower incidence of AFib after CPAP initiation if this arrhythmia has never been documented.1 Further investigation will be needed to assess the etiopathogenic relationship between OSA and AF and the physiologic changes induced by CPAP that prevent AFib in some patients with AF. Victor Bazan, PhD Nuria Grau, MD Barcelona, Spain Affiliations: From the Electrophysiology Unit (Dr Bazan), Cardiology Department; and Sleep Disorders Unit (Dr Grau), Respiratory Medicine Department, Hospital del Mar, Parc de Salut Mar, Universitat Autònoma de Barcelona. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence: Victor Bazan, PhD, Hospital del Mar, Parc de Salut Mar, Universitat Autònoma de Barcelona, 25 Passeig Marítim, 08003 Barcelona, Spain; e-mail: [email protected] © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-0999
References 1. Bazan V, Grau N, Valles E, et al. Obstructive sleep apnea in patients with typical atrial flutter: prevalence and impact on arrhythmia control outcome. Chest. 2013;143(5):1277-1283. 2. Tongers J, Schwerdtfeger B, Klein G, et al. Incidence and clinical relevance of supraventricular tachyarrhythmias in pulmonary hypertension. Am Heart J. 2007;153(1):127-132. 3. Savelieva I, Kakouros N, Kourliouros A, Camm AJ. Upstream therapies for management of atrial fibrillation: review of clinical evidence and implications for European Society of Cardiology guidelines. Part I: primary prevention. Europace. 2011; 13(3):308-328. 4. Da Costa A, Romeyer C, Mourot S, et al. Factors associated with early atrial fibrillation after ablation of common atrial flutter. A single centre prospective study. Eur Heart J. 2002;23(6): 498-506. 5. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005;353(19):2034-2041.
N2 Nodal Involvement in Multiple Primary Lung Cancer Really an Exclusion Criterion? To the Editor: Girard et al1 reported in CHEST (January 2010) a comparison analysis of seven patients with multiple lung adenocarcinomas benchmarked on the epidermal growth factor receptor (EGFR) and Kirsten-rat sarcoma 2 viral oncogene homolog clonality status, which we read with interest and has instigated some reflections. Martini-Melamed (MM) criteria outlined a clinical and diagnostic classification of multiple primary lung cancers (MPLCs)2; today, American College of Chest Physicians (ACCP) guidelines provided a new MPLC classification.3 Both MM and ACCP criteria are used to classify an MPLC case as primary metastatic or true synchronous/metachronous multiple. Furthermore, none of these criteria incorporate information on molecular status to distinguish multiple primary from metastatic disease. The new diagnostic algorithm described by Takamochi and colleagues4 is based on the assessment of EGFR-Kirsten-rat sarcoma 2 viral oncogene homolog to achieve a correct definition of the clonality status among multiple lung adenocarcinomas and, in turn, is used as a differential diagnosis criterion. With this algorithm, Takamochi and colleagues4 could easily detect significant discrepancies in existing clinical criteria in 36 patients they thoroughly examined to assess the difference between true primary and metastatic disease. Similar evidence was reported in Girard et al,1 thus, confirming the inherent limitations of the MM/ACCP criteria. Moreover, Takuwa et al5 advocated for molecular-based stratification criteria by detailing a case of multiple synchronous lung adenocarcinomas harboring an L858R mutation within exon 21 of EGFR in the middle-lobe tumor and subcarinal nodes but not in the upperlobe tumor. In the setting where MM/ACCP criteria are taken into account, the diagnosis of N2 nodal involvement defines synchronous multiple tumors as metastatic lesions; however, these data might suggest that the number of multiple primary adenocarcinomas could be higher than what is observed if only MM/ACCP criteria are taken into account. On the other hand, very few reports compare the clonality status of primary tumors and lymph node metastases6: of 56 non-small cell lung cancers, the molecular appearance in the primary cancer and its lymph node metastasis were concordant in 92.9% and 69.6% by p53 and EGFR status, respectively. According to the high concordance between the clonality of primary tumors with metastatic spread to the lymph nodes, it could be suggested that, in the case of multiple adenocarcinomas, a clonality status evaluation in the mediastinal lymph node metastasis should also be performed. We would appreciate the authors’ opinion about whether the assessment of the clonal lymph node status of their series of seven patients would be a valuable piece of information.
714
Downloaded From: http://journal.publications.chestnet.org/ by David Kinnison on 08/06/2013
Giovanni Leuzzi, MD Alfredo Cesario, MD Marco Chiappetta, MD Stefano Margaritora, PhD Venanzio Porziella, MD Elisa Meacci, MD Maria L. Vita, MD Maria T. Congedo, MD Pierluigi Granone, PhD Rome, Italy
Correspondence