Subclinical impairment of dynamic left ventricular systolic and diastolic function in patients with obstructive sleep apnea and preserved left ventricular ejection fraction
Identifieur interne : 000108 ( Pmc/Corpus ); précédent : 000107; suivant : 000109Subclinical impairment of dynamic left ventricular systolic and diastolic function in patients with obstructive sleep apnea and preserved left ventricular ejection fraction
Auteurs : Antonello D Ndrea ; Angelo Canora ; Simona Sperlongano ; Domenico Galati ; Serena Zanotta ; Giorgio Emanuele Polistina ; Carmine Nicoletta ; Giacomo Ghinassi ; Maurizio Galderisi ; Alessandro Sanduzzi Zamparelli ; Patrizio Lancellotti ; Marialuisa BocchinoSource :
- BMC Pulmonary Medicine [ 1471-2466 ] ; 2020.
Abstract
Hypoxia affects myocardial oxygen supply resulting in subclinical cardiac dysfunction in obstructive sleep apnea (OSA) patients, with cardiovascular complications being associated with increased oxidative burst (OB). The aims of our study were to assess left ventricular (LV) dynamic myocardial deformation and diastolic reserve at rest and upon exercise, along with OB determination in this patients subset.
Conventional echocardiography, Doppler myocardial imaging and LV 2D speckle tracking echocardiography were performed in 55 OSA patients with preserved LV ejection fraction (EF) and 35 age and sex-comparable healthy controls. Peripheral OB levels were evaluated by flow cytometry.
Despite comparable LVEF, LV global longitudinal strain (GLS) was significantly reduced in OSA at rest (− 13.4 ± 3.8 vs − 18.4 ± 3.3 in controls,
Evaluation of diastolic function and myocardial deformation during exercise is feasible through stress echocardiography. OSA patients with preserved LVEF show subclinical LV systolic dysfunction, impaired LV systolic and diastolic reserve, reduced exercise tolerance, and increased peripheral levels of OB. Therapy aimed at increasing LV diastolic function reserve might improve the quality of life and exercise tolerability in OSA patients.
Url:
DOI: 10.1186/s12890-020-1099-9
PubMed: 32223761
PubMed Central: 7103071
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PMC:7103071Le document en format XML
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<author><name sortKey="Ghinassi, Giacomo" sort="Ghinassi, Giacomo" uniqKey="Ghinassi G" first="Giacomo" last="Ghinassi">Giacomo Ghinassi</name>
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<author><name sortKey="Galderisi, Maurizio" sort="Galderisi, Maurizio" uniqKey="Galderisi M" first="Maurizio" last="Galderisi">Maurizio Galderisi</name>
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<author><name sortKey="Zamparelli, Alessandro Sanduzzi" sort="Zamparelli, Alessandro Sanduzzi" uniqKey="Zamparelli A" first="Alessandro Sanduzzi" last="Zamparelli">Alessandro Sanduzzi Zamparelli</name>
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<author><name sortKey="Lancellotti, Patrizio" sort="Lancellotti, Patrizio" uniqKey="Lancellotti P" first="Patrizio" last="Lancellotti">Patrizio Lancellotti</name>
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<author><name sortKey="Bocchino, Marialuisa" sort="Bocchino, Marialuisa" uniqKey="Bocchino M" first="Marialuisa" last="Bocchino">Marialuisa Bocchino</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Subclinical impairment of dynamic left ventricular systolic and diastolic function in patients with obstructive sleep apnea and preserved left ventricular ejection fraction</title>
<author><name sortKey="D Ndrea, Antonello" sort="D Ndrea, Antonello" uniqKey="D Ndrea A" first="Antonello" last="D Ndrea">Antonello D Ndrea</name>
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<author><name sortKey="Canora, Angelo" sort="Canora, Angelo" uniqKey="Canora A" first="Angelo" last="Canora">Angelo Canora</name>
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Via L. Bianchi, 5, 80131 Naples, Italy</nlm:aff>
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<author><name sortKey="Sperlongano, Simona" sort="Sperlongano, Simona" uniqKey="Sperlongano S" first="Simona" last="Sperlongano">Simona Sperlongano</name>
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</institution-wrap>
Naples, Italy</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Galati, Domenico" sort="Galati, Domenico" uniqKey="Galati D" first="Domenico" last="Galati">Domenico Galati</name>
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Naples, Italy</nlm:aff>
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<author><name sortKey="Zanotta, Serena" sort="Zanotta, Serena" uniqKey="Zanotta S" first="Serena" last="Zanotta">Serena Zanotta</name>
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Naples, Italy</nlm:aff>
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<author><name sortKey="Polistina, Giorgio Emanuele" sort="Polistina, Giorgio Emanuele" uniqKey="Polistina G" first="Giorgio Emanuele" last="Polistina">Giorgio Emanuele Polistina</name>
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Via L. Bianchi, 5, 80131 Naples, Italy</nlm:aff>
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<author><name sortKey="Nicoletta, Carmine" sort="Nicoletta, Carmine" uniqKey="Nicoletta C" first="Carmine" last="Nicoletta">Carmine Nicoletta</name>
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</institution-wrap>
Via L. Bianchi, 5, 80131 Naples, Italy</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ghinassi, Giacomo" sort="Ghinassi, Giacomo" uniqKey="Ghinassi G" first="Giacomo" last="Ghinassi">Giacomo Ghinassi</name>
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<institution>Department of Clinical Medicine and Surgery, Respiratory Medicine Section,</institution>
<institution>Federico II University (at Monaldi Hospital),</institution>
</institution-wrap>
Via L. Bianchi, 5, 80131 Naples, Italy</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Galderisi, Maurizio" sort="Galderisi, Maurizio" uniqKey="Galderisi M" first="Maurizio" last="Galderisi">Maurizio Galderisi</name>
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<institution-id institution-id-type="GRID">grid.411293.c</institution-id>
<institution>Department of Advanced Biomedical Sciences,</institution>
<institution>Federico II University Hospital Via S. Pansini 5,</institution>
</institution-wrap>
Naples, Italy</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zamparelli, Alessandro Sanduzzi" sort="Zamparelli, Alessandro Sanduzzi" uniqKey="Zamparelli A" first="Alessandro Sanduzzi" last="Zamparelli">Alessandro Sanduzzi Zamparelli</name>
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<institution-id institution-id-type="GRID">grid.4691.a</institution-id>
<institution>Department of Clinical Medicine and Surgery, Respiratory Medicine Section,</institution>
<institution>Federico II University (at Monaldi Hospital),</institution>
</institution-wrap>
Via L. Bianchi, 5, 80131 Naples, Italy</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lancellotti, Patrizio" sort="Lancellotti, Patrizio" uniqKey="Lancellotti P" first="Patrizio" last="Lancellotti">Patrizio Lancellotti</name>
<affiliation><nlm:aff id="Aff6">CHU de Liége, Service de Cardiologie, Liege, Belgium</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bocchino, Marialuisa" sort="Bocchino, Marialuisa" uniqKey="Bocchino M" first="Marialuisa" last="Bocchino">Marialuisa Bocchino</name>
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<institution-id institution-id-type="GRID">grid.4691.a</institution-id>
<institution>Department of Clinical Medicine and Surgery, Respiratory Medicine Section,</institution>
<institution>Federico II University (at Monaldi Hospital),</institution>
</institution-wrap>
Via L. Bianchi, 5, 80131 Naples, Italy</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">BMC Pulmonary Medicine</title>
<idno type="eISSN">1471-2466</idno>
<imprint><date when="2020">2020</date>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p id="Par1">Hypoxia affects myocardial oxygen supply resulting in subclinical cardiac dysfunction in obstructive sleep apnea (OSA) patients, with cardiovascular complications being associated with increased oxidative burst (OB). The aims of our study were to assess left ventricular (LV) dynamic myocardial deformation and diastolic reserve at rest and upon exercise, along with OB determination in this patients subset.</p>
</sec>
<sec><title>Methods</title>
<p id="Par2">Conventional echocardiography, Doppler myocardial imaging and LV 2D speckle tracking echocardiography were performed in 55 OSA patients with preserved LV ejection fraction (EF) and 35 age and sex-comparable healthy controls. Peripheral OB levels were evaluated by flow cytometry.</p>
</sec>
<sec><title>Results</title>
<p id="Par3">Despite comparable LVEF, LV global longitudinal strain (GLS) was significantly reduced in OSA at rest (− 13.4 ± 3.8 vs − 18.4 ± 3.3 in controls, <italic>P</italic>
< 0.001) and at peak exercise (− 15.8 ± 2.6 vs − 23.4 ± 4.3, <italic>P</italic>
< 0.001). Systolic pulmonary artery pressure (sPAP) and E/E′ ratios increase during effort were higher in OSA than in controls (ΔsPAP 44.3% ± 6.4 vs 32.3% ± 5.5, <italic>P</italic>
< 0.0001, and ΔE/E’ 87.5% ± 3.5 vs 25.4% ± 3.3, <italic>P</italic>
< 0.0001, respectively). The best correlate of E/E′ at peak stress was peak exertion capacity (<italic>r</italic>
= − 0.50, <italic>P</italic>
< 0.001). OB was also increased in OSA patients (<italic>P</italic>
= 0.001) but, unlike OSA severity, was not associated with LV diastolic dysfunction.</p>
</sec>
<sec><title>Conclusions</title>
<p id="Par4">Evaluation of diastolic function and myocardial deformation during exercise is feasible through stress echocardiography. OSA patients with preserved LVEF show subclinical LV systolic dysfunction, impaired LV systolic and diastolic reserve, reduced exercise tolerance, and increased peripheral levels of OB. Therapy aimed at increasing LV diastolic function reserve might improve the quality of life and exercise tolerability in OSA patients.</p>
</sec>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Qaseem, A" uniqKey="Qaseem A">A Qaseem</name>
</author>
<author><name sortKey="Dallas, P" uniqKey="Dallas P">P Dallas</name>
</author>
<author><name sortKey="Owens, Dk" uniqKey="Owens D">DK Owens</name>
</author>
<author><name sortKey="Starkey, M" uniqKey="Starkey M">M Starkey</name>
</author>
<author><name sortKey="Holty, Jec" uniqKey="Holty J">JEC Holty</name>
</author>
<author><name sortKey="Shekelle, P" uniqKey="Shekelle P">P Shekelle</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Phillips, B" uniqKey="Phillips B">B Phillips</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Leung, Rst" uniqKey="Leung R">RST Leung</name>
</author>
<author><name sortKey="Bradley, Td" uniqKey="Bradley T">TD Bradley</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Haruki, N" uniqKey="Haruki N">N Haruki</name>
</author>
<author><name sortKey="Takeuchi, M" uniqKey="Takeuchi M">M Takeuchi</name>
</author>
<author><name sortKey="Kanazawa, Y" uniqKey="Kanazawa Y">Y Kanazawa</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bodez, D" uniqKey="Bodez D">D Bodez</name>
</author>
<author><name sortKey="Damy, T" uniqKey="Damy T">T Damy</name>
</author>
<author><name sortKey="Soulat Dufour, L" uniqKey="Soulat Dufour L">L Soulat-Dufour</name>
</author>
<author><name sortKey="Meuleman, C" uniqKey="Meuleman C">C Meuleman</name>
</author>
<author><name sortKey="Cohen, A" uniqKey="Cohen A">A Cohen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shim, Cy" uniqKey="Shim C">CY Shim</name>
</author>
<author><name sortKey="Kim, D" uniqKey="Kim D">D Kim</name>
</author>
<author><name sortKey="Park, S" uniqKey="Park S">S Park</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cetin, S" uniqKey="Cetin S">S Cetin</name>
</author>
<author><name sortKey="Vural, M" uniqKey="Vural M">M Vural</name>
</author>
<author><name sortKey="Akdemir, R" uniqKey="Akdemir R">R Akdemir</name>
</author>
<author><name sortKey="Firat, H" uniqKey="Firat H">H Firat</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Butt, M" uniqKey="Butt M">M Butt</name>
</author>
<author><name sortKey="Dwivedi, G" uniqKey="Dwivedi G">G Dwivedi</name>
</author>
<author><name sortKey="Shantsila, A" uniqKey="Shantsila A">A Shantsila</name>
</author>
<author><name sortKey="Khair, Oa" uniqKey="Khair O">OA Khair</name>
</author>
<author><name sortKey="Lip, Gyh" uniqKey="Lip G">GYH Lip</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lira, Ab" uniqKey="Lira A">AB Lira</name>
</author>
<author><name sortKey="De Sousa Rodrigues, Cf" uniqKey="De Sousa Rodrigues C">CF de Sousa Rodrigues</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Passali, D" uniqKey="Passali D">D Passali</name>
</author>
<author><name sortKey="Corallo, G" uniqKey="Corallo G">G Corallo</name>
</author>
<author><name sortKey="Yaremchuk, S" uniqKey="Yaremchuk S">S Yaremchuk</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hopps, E" uniqKey="Hopps E">E Hopps</name>
</author>
<author><name sortKey="Lo Presti, R" uniqKey="Lo Presti R">R Lo Presti</name>
</author>
<author><name sortKey="Montana, M" uniqKey="Montana M">M Montana</name>
</author>
<author><name sortKey="Canino, B" uniqKey="Canino B">B Canino</name>
</author>
<author><name sortKey="Calandrino, V" uniqKey="Calandrino V">V Calandrino</name>
</author>
<author><name sortKey="Caimi, G" uniqKey="Caimi G">G Caimi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Asker, S" uniqKey="Asker S">S Asker</name>
</author>
<author><name sortKey="Asker, M" uniqKey="Asker M">M Asker</name>
</author>
<author><name sortKey="Sarikaya, E" uniqKey="Sarikaya E">E Sarikaya</name>
</author>
<author><name sortKey="Sunnetcioglu, A" uniqKey="Sunnetcioglu A">A Sunnetcioglu</name>
</author>
<author><name sortKey="Aslan, M" uniqKey="Aslan M">M Aslan</name>
</author>
<author><name sortKey="Demir, H" uniqKey="Demir H">H Demir</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Berry, Rb" uniqKey="Berry R">RB Berry</name>
</author>
<author><name sortKey="Budhiraja, R" uniqKey="Budhiraja R">R Budhiraja</name>
</author>
<author><name sortKey="Gottlieb, Dj" uniqKey="Gottlieb D">DJ Gottlieb</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Levi Valensi, P" uniqKey="Levi Valensi P">P Levi-Valensi</name>
</author>
<author><name sortKey="Weitzenblum, E" uniqKey="Weitzenblum E">E Weitzenblum</name>
</author>
<author><name sortKey="Rida, Z" uniqKey="Rida Z">Z Rida</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fletcher, Ec" uniqKey="Fletcher E">EC Fletcher</name>
</author>
<author><name sortKey="Miller, J" uniqKey="Miller J">J Miller</name>
</author>
<author><name sortKey="Divine, Gw" uniqKey="Divine G">GW Divine</name>
</author>
<author><name sortKey="Fletcher, Jg" uniqKey="Fletcher J">JG Fletcher</name>
</author>
<author><name sortKey="Miller, T" uniqKey="Miller T">T Miller</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Miller, Mr" uniqKey="Miller M">MR Miller</name>
</author>
<author><name sortKey="Hankinson, J" uniqKey="Hankinson J">J Hankinson</name>
</author>
<author><name sortKey="Brusasco, V" uniqKey="Brusasco V">V Brusasco</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wanger, J" uniqKey="Wanger J">J Wanger</name>
</author>
<author><name sortKey="Clausen, Jl" uniqKey="Clausen J">JL Clausen</name>
</author>
<author><name sortKey="Coates, A" uniqKey="Coates A">A Coates</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Macintyre, N" uniqKey="Macintyre N">N MacIntyre</name>
</author>
<author><name sortKey="Crapo, Ro" uniqKey="Crapo R">RO Crapo</name>
</author>
<author><name sortKey="Viegi, G" uniqKey="Viegi G">G Viegi</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Lang, Rm" uniqKey="Lang R">RM Lang</name>
</author>
<author><name sortKey="Badano, Lp" uniqKey="Badano L">LP Badano</name>
</author>
<author><name sortKey="Mor Avi, V" uniqKey="Mor Avi V">V Mor-Avi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Voigt, Ju" uniqKey="Voigt J">JU Voigt</name>
</author>
<author><name sortKey="Pedrizzetti, G" uniqKey="Pedrizzetti G">G Pedrizzetti</name>
</author>
<author><name sortKey="Lysyansky, P" uniqKey="Lysyansky P">P Lysyansky</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nagueh, Sf" uniqKey="Nagueh S">SF Nagueh</name>
</author>
<author><name sortKey="Smiseth, Oa" uniqKey="Smiseth O">OA Smiseth</name>
</author>
<author><name sortKey="Appleton, Cp" uniqKey="Appleton C">CP Appleton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lancellotti, P" uniqKey="Lancellotti P">P Lancellotti</name>
</author>
<author><name sortKey="Pellikka, Pa" uniqKey="Pellikka P">PA Pellikka</name>
</author>
<author><name sortKey="Budts, W" uniqKey="Budts W">W Budts</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Marin, Jm" uniqKey="Marin J">JM Marin</name>
</author>
<author><name sortKey="Carrizo, Sj" uniqKey="Carrizo S">SJ Carrizo</name>
</author>
<author><name sortKey="Vicente, E" uniqKey="Vicente E">E Vicente</name>
</author>
<author><name sortKey="Agusti, Ag" uniqKey="Agusti A">AG Agusti</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Punjabi, Nm" uniqKey="Punjabi N">NM Punjabi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shahar, E" uniqKey="Shahar E">E Shahar</name>
</author>
<author><name sortKey="Whitney, Cw" uniqKey="Whitney C">CW Whitney</name>
</author>
<author><name sortKey="Redline, S" uniqKey="Redline S">S Redline</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yaggi, Hk" uniqKey="Yaggi H">HK Yaggi</name>
</author>
<author><name sortKey="Concato, J" uniqKey="Concato J">J Concato</name>
</author>
<author><name sortKey="Kernan, Wn" uniqKey="Kernan W">WN Kernan</name>
</author>
<author><name sortKey="Lichtman, Jh" uniqKey="Lichtman J">JH Lichtman</name>
</author>
<author><name sortKey="Brass, Lm" uniqKey="Brass L">LM Brass</name>
</author>
<author><name sortKey="Mohsenin, V" uniqKey="Mohsenin V">V Mohsenin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gondi, S" uniqKey="Gondi S">S Gondi</name>
</author>
<author><name sortKey="Dokainish, H" uniqKey="Dokainish H">H Dokainish</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="D Ndrea, A" uniqKey="D Ndrea A">A D’Andrea</name>
</author>
<author><name sortKey="Martone, F" uniqKey="Martone F">F Martone</name>
</author>
<author><name sortKey="Liccardo, B" uniqKey="Liccardo B">B Liccardo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Buonauro, A" uniqKey="Buonauro A">A Buonauro</name>
</author>
<author><name sortKey="Galderisi, M" uniqKey="Galderisi M">M Galderisi</name>
</author>
<author><name sortKey="Santoro, C" uniqKey="Santoro C">C Santoro</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bodez, D" uniqKey="Bodez D">D Bodez</name>
</author>
<author><name sortKey="Lang, S" uniqKey="Lang S">S Lang</name>
</author>
<author><name sortKey="Meuleman, C" uniqKey="Meuleman C">C Meuleman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Arias, Ma" uniqKey="Arias M">MA Arias</name>
</author>
<author><name sortKey="Garcia Rio, F" uniqKey="Garcia Rio F">F Garcia-Rio</name>
</author>
<author><name sortKey="Alonso Fernandez, A" uniqKey="Alonso Fernandez A">A Alonso-Fernandez</name>
</author>
<author><name sortKey="Mediano, O" uniqKey="Mediano O">O Mediano</name>
</author>
<author><name sortKey="Martinez, I" uniqKey="Martinez I">I Martinez</name>
</author>
<author><name sortKey="Villamor, J" uniqKey="Villamor J">J Villamor</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Baguet, Jp" uniqKey="Baguet J">JP Baguet</name>
</author>
<author><name sortKey="Barone Rochette, G" uniqKey="Barone Rochette G">G Barone-Rochette</name>
</author>
<author><name sortKey="Levy, P" uniqKey="Levy P">P Levy</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fung, Jw" uniqKey="Fung J">JW Fung</name>
</author>
<author><name sortKey="Li, Ts" uniqKey="Li T">TS Li</name>
</author>
<author><name sortKey="Choy, Dk" uniqKey="Choy D">DK Choy</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ha, Jw" uniqKey="Ha J">JW Ha</name>
</author>
<author><name sortKey="Lulic, F" uniqKey="Lulic F">F Lulic</name>
</author>
<author><name sortKey="Bailey, Kr" uniqKey="Bailey K">KR Bailey</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Oh, Jk" uniqKey="Oh J">JK Oh</name>
</author>
<author><name sortKey="Kane, Gc" uniqKey="Kane G">GC Kane</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kane, Gc" uniqKey="Kane G">GC Kane</name>
</author>
<author><name sortKey="Sachdev, A" uniqKey="Sachdev A">A Sachdev</name>
</author>
<author><name sortKey="Villarraga, Hr" uniqKey="Villarraga H">HR Villarraga</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ha, Jw" uniqKey="Ha J">JW Ha</name>
</author>
<author><name sortKey="Choi, D" uniqKey="Choi D">D Choi</name>
</author>
<author><name sortKey="Park, S" uniqKey="Park S">S Park</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Burgess, Mi" uniqKey="Burgess M">MI Burgess</name>
</author>
<author><name sortKey="Jenkins, C" uniqKey="Jenkins C">C Jenkins</name>
</author>
<author><name sortKey="Sharman, Je" uniqKey="Sharman J">JE Sharman</name>
</author>
<author><name sortKey="Marwick, Th" uniqKey="Marwick T">TH Marwick</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ha, Jw" uniqKey="Ha J">JW Ha</name>
</author>
<author><name sortKey="Oh, Jk" uniqKey="Oh J">JK Oh</name>
</author>
<author><name sortKey="Pellikka, Pa" uniqKey="Pellikka P">PA Pellikka</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">BMC Pulm Med</journal-id>
<journal-id journal-id-type="iso-abbrev">BMC Pulm Med</journal-id>
<journal-title-group><journal-title>BMC Pulmonary Medicine</journal-title>
</journal-title-group>
<issn pub-type="epub">1471-2466</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">32223761</article-id>
<article-id pub-id-type="pmc">7103071</article-id>
<article-id pub-id-type="publisher-id">1099</article-id>
<article-id pub-id-type="doi">10.1186/s12890-020-1099-9</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Subclinical impairment of dynamic left ventricular systolic and diastolic function in patients with obstructive sleep apnea and preserved left ventricular ejection fraction</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes" equal-contrib="yes"><name><surname>D’Andrea</surname>
<given-names>Antonello</given-names>
</name>
<address><email>antonellodandrea@libero.it</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Canora</surname>
<given-names>Angelo</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sperlongano</surname>
<given-names>Simona</given-names>
</name>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Galati</surname>
<given-names>Domenico</given-names>
</name>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zanotta</surname>
<given-names>Serena</given-names>
</name>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Polistina</surname>
<given-names>Giorgio Emanuele</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nicoletta</surname>
<given-names>Carmine</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ghinassi</surname>
<given-names>Giacomo</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author" deceased="yes"><name><surname>Galderisi</surname>
<given-names>Maurizio</given-names>
</name>
<xref ref-type="aff" rid="Aff5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zamparelli</surname>
<given-names>Alessandro Sanduzzi</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lancellotti</surname>
<given-names>Patrizio</given-names>
</name>
<xref ref-type="aff" rid="Aff6">6</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-5477-072X</contrib-id>
<name><surname>Bocchino</surname>
<given-names>Marialuisa</given-names>
</name>
<address><email>marialuisa.bocchino@unina.it</email>
</address>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<aff id="Aff1"><label>1</label>
Unit of Cardiology and Intensive Care, Umberto I Hospital, Viale San Francesco, 84014 Nocera Inferiore (Salerno), Italy</aff>
<aff id="Aff2"><label>2</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0790 385X</institution-id>
<institution-id institution-id-type="GRID">grid.4691.a</institution-id>
<institution>Department of Clinical Medicine and Surgery, Respiratory Medicine Section,</institution>
<institution>Federico II University (at Monaldi Hospital),</institution>
</institution-wrap>
Via L. Bianchi, 5, 80131 Naples, Italy</aff>
<aff id="Aff3"><label>3</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1755 4122</institution-id>
<institution-id institution-id-type="GRID">grid.416052.4</institution-id>
<institution>Unit of Cardiology, Department of Translational Medical Sciences,</institution>
<institution>University of Campania “Luigi Vanvitelli”, Monaldi Hospital,</institution>
</institution-wrap>
Naples, Italy</aff>
<aff id="Aff4"><label>4</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0807 2568</institution-id>
<institution-id institution-id-type="GRID">grid.417893.0</institution-id>
<institution>Haematology-Oncology and Stem Cell Transplantation Unit, Department of Haematology and Innovative Therapies,</institution>
<institution>Istituto Nazionale Tumori- IRCCS Fondazione G. Pascale,</institution>
</institution-wrap>
Naples, Italy</aff>
<aff id="Aff5"><label>5</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1754 9702</institution-id>
<institution-id institution-id-type="GRID">grid.411293.c</institution-id>
<institution>Department of Advanced Biomedical Sciences,</institution>
<institution>Federico II University Hospital Via S. Pansini 5,</institution>
</institution-wrap>
Naples, Italy</aff>
<aff id="Aff6"><label>6</label>
CHU de Liége, Service de Cardiologie, Liege, Belgium</aff>
</contrib-group>
<pub-date pub-type="epub"><day>29</day>
<month>3</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>29</day>
<month>3</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="collection"><year>2020</year>
</pub-date>
<volume>20</volume>
<elocation-id>76</elocation-id>
<history><date date-type="received"><day>8</day>
<month>8</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>24</day>
<month>2</month>
<year>2020</year>
</date>
</history>
<permissions><copyright-statement>© The Author(s). 2020</copyright-statement>
<license license-type="OpenAccess"><license-p><bold>Open Access</bold>
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>
) applies to the data made available in this article, unless otherwise stated in a credit line to the data.</license-p>
</license>
</permissions>
<abstract id="Abs1"><sec><title>Background</title>
<p id="Par1">Hypoxia affects myocardial oxygen supply resulting in subclinical cardiac dysfunction in obstructive sleep apnea (OSA) patients, with cardiovascular complications being associated with increased oxidative burst (OB). The aims of our study were to assess left ventricular (LV) dynamic myocardial deformation and diastolic reserve at rest and upon exercise, along with OB determination in this patients subset.</p>
</sec>
<sec><title>Methods</title>
<p id="Par2">Conventional echocardiography, Doppler myocardial imaging and LV 2D speckle tracking echocardiography were performed in 55 OSA patients with preserved LV ejection fraction (EF) and 35 age and sex-comparable healthy controls. Peripheral OB levels were evaluated by flow cytometry.</p>
</sec>
<sec><title>Results</title>
<p id="Par3">Despite comparable LVEF, LV global longitudinal strain (GLS) was significantly reduced in OSA at rest (− 13.4 ± 3.8 vs − 18.4 ± 3.3 in controls, <italic>P</italic>
< 0.001) and at peak exercise (− 15.8 ± 2.6 vs − 23.4 ± 4.3, <italic>P</italic>
< 0.001). Systolic pulmonary artery pressure (sPAP) and E/E′ ratios increase during effort were higher in OSA than in controls (ΔsPAP 44.3% ± 6.4 vs 32.3% ± 5.5, <italic>P</italic>
< 0.0001, and ΔE/E’ 87.5% ± 3.5 vs 25.4% ± 3.3, <italic>P</italic>
< 0.0001, respectively). The best correlate of E/E′ at peak stress was peak exertion capacity (<italic>r</italic>
= − 0.50, <italic>P</italic>
< 0.001). OB was also increased in OSA patients (<italic>P</italic>
= 0.001) but, unlike OSA severity, was not associated with LV diastolic dysfunction.</p>
</sec>
<sec><title>Conclusions</title>
<p id="Par4">Evaluation of diastolic function and myocardial deformation during exercise is feasible through stress echocardiography. OSA patients with preserved LVEF show subclinical LV systolic dysfunction, impaired LV systolic and diastolic reserve, reduced exercise tolerance, and increased peripheral levels of OB. Therapy aimed at increasing LV diastolic function reserve might improve the quality of life and exercise tolerability in OSA patients.</p>
</sec>
</abstract>
<kwd-group xml:lang="en"><title>Keywords</title>
<kwd>Obstructive sleep apnea</kwd>
<kwd>Exercise echocardiography</kwd>
<kwd>2D speckle tracking echocardiography</kwd>
<kwd>Diastolic function</kwd>
<kwd>Oxidative burst</kwd>
</kwd-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2020</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body><sec id="Sec1"><title>Background</title>
<p id="Par31">Obstructive sleep apnea (OSA) is characterized by repeated episodes of partial or complete upper airways collapse, resulting in apnea and hypopnea events, intermittent hypoxemia and frequent arousals [<xref ref-type="bibr" rid="CR1">1</xref>
]. OSA is an increasing health problem, often associated with cardiovascular disorders, including left (LV) and right ventricular (RV) dysfunction, arterial hypertension, coronary artery disease, heart failure, and arrhythmias [<xref ref-type="bibr" rid="CR2">2</xref>
, <xref ref-type="bibr" rid="CR3">3</xref>
]. Repetitive hypoxia episodes adversely affect the interaction between myocardial oxygen demand and supply, with development of subclinical systolic dysfunction [<xref ref-type="bibr" rid="CR4">4</xref>
]. Furthermore, hormonal and metabolic dysregulation, oxidative burst (OB), systemic inflammation and mechanical hemodynamic disturbances lead to LV remodeling and diastolic dysfunction [<xref ref-type="bibr" rid="CR5">5</xref>
–<xref ref-type="bibr" rid="CR8">8</xref>
]. There is evidence of a consistent relationship between OB and OSA [<xref ref-type="bibr" rid="CR9">9</xref>
]. OB has been suggested as a marker of upper airway obstructive episodes and hypoxemia causing local oropharyngeal inflammation [<xref ref-type="bibr" rid="CR10">10</xref>
], and has been associated with cardiovascular complications [<xref ref-type="bibr" rid="CR11">11</xref>
, <xref ref-type="bibr" rid="CR12">12</xref>
].</p>
<p id="Par32">On this basis, we hypothesized that OSA patients with preserved LV ejection fraction (LVEF) would have dynamic abnormalities in LV myocardial deformation and/or increased dynamic diastolic stiffness. The aims of our study were to assess, by means of 2D speckle tracking echocardiography (2DSTE) and diastolic parameters, LV myocardial deformation and diastolic function indexes both at rest and during exercise, mainly focusing on the systolic and diastolic reserve. Reproducibility of 2DSTE measurements was also assessed. In addition, we evaluated peripheral levels of OB as we aimed to address any relationship with basal and dynamic heart function parameters.</p>
</sec>
<sec id="Sec2"><title>Methods</title>
<sec id="Sec3"><title>Study population</title>
<p id="Par33">From October 2017 to May 2018, 55 consecutive patients affected by moderate-severe OSA, referred to our Respiratory Medicine Division, were enrolled. Patients with a clinical history of concomitant lung disease (including chronic obstructive pulmonary disease, bronchial asthma, interstitial lung diseases), coronary artery disease, valvular heart disease, congestive heart failure, arrhythmias, and pulmonary hypertension were excluded. All OSA patients were not being treated with continuous positive airway pressure (CPAP). Thirty-five age- and sex-comparable healthy subjects referred to our attention for a voluntary cardiovascular screening were enrolled as controls. The study was conducted in accordance with the amended Declaration of Helsinki. The local Ethics committee approved the study and all individuals gave written informed consent.</p>
</sec>
<sec id="Sec4"><title>OSA assessment</title>
<p id="Par34">OSA diagnosis was performed with home overnight cardiorespiratory polygraphy using a VitalNight data acquisition and analysis system (AirLiquide Medical System, Rangendigen, Germany) according to reference guidelines [13]. Data were analysed by trained sleep physicians with more than 3-yr experience and OSA severity was graded with the apnea/hypopnea index (AHI) according to accepted criteria [<xref ref-type="bibr" rid="CR13">13</xref>
]. Nocturnal respiratory failure (NRF) was defined if t90% was ≥30% or there was at least one period of 5 min minimum with a SpO<sub>2</sub>
≤ 90% with a nadir of 85% during registration [<xref ref-type="bibr" rid="CR14">14</xref>
, <xref ref-type="bibr" rid="CR15">15</xref>
]. t90 is the percentage of time spent with a SpO<sub>2</sub>
< 90%.</p>
</sec>
<sec id="Sec5"><title>Lung function</title>
<p id="Par35">Spirometry, lung volumes measurement and determination of the haemoglobin (Hb)-adjusted single-breath diffusing lung capacity of the carbon monoxide (DLCO<sub>sb</sub>
) were performed using a computer-assisted spirometer (Quark PFT 2008 Suite Version Cosmed Ltd., Rome, Italy) according to international standards [<xref ref-type="bibr" rid="CR16">16</xref>
–<xref ref-type="bibr" rid="CR18">18</xref>
]. The 6 min walking test (6MWT) was performed by trained hospital staff according to guidelines [<xref ref-type="bibr" rid="CR19">19</xref>
]. Arterial blood gas analysis at rest was also obtained.</p>
</sec>
<sec id="Sec6"><title>Heart study</title>
<p id="Par36">Standard trans-thoracic echocardiography, Doppler evaluation and strain analysis were performed at rest and at peak effort using market available equipment (Vivid E9 - GE Healthcare, Milwaukee, WI, USA; MyLab Alpha ESAOTE, Florence, Italy). All measurements were performed at our Cardiology Unit and independently assessed by two cardiologists expert in echocardiography, according to current recommendations [<xref ref-type="bibr" rid="CR20">20</xref>
–<xref ref-type="bibr" rid="CR22">22</xref>
]. <italic>Rest echocardiography:</italic>
LV ejection fraction (EF) and LV global longitudinal strain (GLS) were evaluated as systolic function indexes. LVEF was calculated using the Simpson biplane method, from the apical 4- and 2-chamber views. A biplane LVEF ≥52% for men and ≥ 54% for women were considered normal [<xref ref-type="bibr" rid="CR20">20</xref>
]. For strain calculation, the endocardial borders of the LV myocardial walls were traced by a point-and-click approach, in the end-systolic frame of the 2D images, from the apical 3-, 4-, and 2-chamber views. The tracking algorithm followed the endocardium during all the cardiac cycle. Basal, mid, and apical regions of interest were created and segments that failed to track were manually adjusted. Longitudinal strains for each of 18 segments were measured and LV GLS was calculated as the mean strain of all the segments. The tracking process and conversion to Lagrangian strains were performed offline using dedicated software (EchoPAC PC 2D strain, GE Healthcare, Milwaukee, WI, USA). We defined impaired GLS as > − 20% (a less negative value reflects a more impaired GLS) [<xref ref-type="bibr" rid="CR20">20</xref>
, <xref ref-type="bibr" rid="CR21">21</xref>
]. The following diastolic function parameters were measured by pulsed wave (PW) Doppler and tissue Doppler imaging (TDI), in apical 4-chamber view: peak early (E) and late (A) diastolic velocity of the mitral inflow, E/A ratio, peak septal and lateral early myocardial diastolic velocity (e′) and average E/e′ ratio. The peak tricuspid regurgitation velocity (TRV) was measured in multiple echocardiographic windows. On the basis of the highest TRV obtained, systolic pulmonary artery pressure (sPAP) was calculated through the Bernoulli’s principle: (4xTRV<sup>2</sup>
) + right atrial pressure (RAP). RAP was estimated by measuring the diameter of the inferior vena cava and its respiratory motion. Left atrial volume index (LAVI) was assessed through biplane area-length method, dividing the left atrial volume by the body surface area (BSA). Atrium acquisitions were made from the apical 4- and 2- chamber views. The presence of more than 2 between average E/e’ > 14, septal e’ < 7 cm/s or lateral e’ < 10 cm/s, TRV > 2.8 m/s (sPAP> 36 mmHg), and LAVI > 34 ml/m<sup>2</sup>
, was considered expression of LV diastolic dysfunction in subjects with normal LVEF [<xref ref-type="bibr" rid="CR22">22</xref>
]. <italic>Exercise stress echocardiography:</italic>
Standard supine bicycle exercise stress echocardiography was performed with incremental steps of 25 W every 2 min [<xref ref-type="bibr" rid="CR23">23</xref>
]. Parameters evaluated at peak exercise included LV GLS as systolic function index, LV diastolic parameters (E, septal and lateral e’ and average E/e’ ratio) and sPAP. An increase in the E/e’ ratio and/or sPAP upon exercise were considered expression of impaired LV diastolic function reserve [<xref ref-type="bibr" rid="CR23">23</xref>
].</p>
</sec>
<sec id="Sec7"><title>Oxidative burst determination</title>
<p id="Par37">Oxidative burst of peripheral leukocytes was measured with the Phagoburst BURSTEST™ (PHAGOBURST™, BD Bioscences, La Jolla, CA, USA), according to the manufacturer’s instruction. Briefly, 100 μl of heparinized whole blood was incubated with opsonized <italic>E.coli</italic>
at 37 °C for 10 min. A sample without stimulus served as negative background control. Dihydrorhodamine (DHR) 123 was added for 10 min to allow the conversion to fluorescent rhodamine 123 upon reactive oxygen species (ROS) production. After erythrocytes were removed and washing, 200 μl of DNA staining solution was added for 10 min to exclude aggregation artifacts. Samples were acquired with a FACS CANTO flow cytometer (BD Biosciences, La Jolla, CA, USA). Analysis was performed with the FACS DIVA software.</p>
</sec>
<sec id="Sec8"><title>Statistical analysis</title>
<p id="Par38">Statistical analyses were performed using a commercially available package (SPSS, Rel. 21.0. 2016, SPSS Inc., Chicago, IL, USA). Variables are presented as mean ± standard deviation (SD). Two-tailed <italic>t</italic>
-test for paired and unpaired data was used to assess changes between groups.</p>
<p id="Par39">Linear regression analyses and partial correlation test by Pearson’s method were used to assess univariate relations. The following variables were included into the analysis: clinical parameters (age, heart rate, oxygen saturation, systolic blood pressure, diastolic blood pressure, body mass index (BMI), risk factors, co-morbidities); lung function, sleep-related and metabolic parameters; standard echocardiographic and 2DSTE parameters. To identify significant independent determinants of resting and dynamic LV diastolic function in OSA patients, their individual association with clinical, functional and echocardiographic variables was assessed by multivariate analysis, using a bidirectional stepwise regression. Variables included in our analysis were all the variables significantly (<italic>p</italic>
< 0.05) associated with the explained variable by univariate analysis. Odds ratios (OR) were calculated using a logistic regression method, and Beta-coefficients were obtained by linear regression method. Values of <italic>p</italic>
< 0.05 were considered significant for all analyses.</p>
<p id="Par40">Receiver operating characteristic (ROC) curve analysis was performed to select optimal cut-off values of echocardiographic parameters. Reproducibility of GLS measurements was determined in all the subjects. Intra-observer variability and inter-observer variability were examined using the coefficient of variation (COV), defined as the ratio of the standard deviation (σ) to the mean (μ) (%), and by Bland-Altman analysis. COV, 95% confidence intervals (CIs), and percent errors were reported.</p>
</sec>
</sec>
<sec id="Sec9"><title>Results</title>
<sec id="Sec10"><title>Peripheral levels of oxidative burst are increased in OSA patients</title>
<p id="Par41">Our study population was composed of 90 subjects, including 55 OSA patients and 35 healthy controls. Main demographic and clinical characteristics are summarized in Table <xref rid="Tab1" ref-type="table">1</xref>
. Lung function was preserved in both study groups (Table <xref rid="Tab1" ref-type="table">1</xref>
), with the exception of forced vital capacity that was slightly lower in OSA patients. Distribution of sleep-related respiratory events is reported in Table <xref rid="Tab1" ref-type="table">1</xref>
. Thirty patients were suffering from severe OSA (54%), while 21 (39%) had a concomitant condition of NRF, as assessed by a t90 > 30% in all cases. In line with previous observations [<xref ref-type="bibr" rid="CR9">9</xref>
–<xref ref-type="bibr" rid="CR11">11</xref>
], levels of OB were significantly increased in OSA patients than in controls (Fig. <xref rid="Fig1" ref-type="fig">1</xref>
). OB was significantly higher in patients with a t90 > 30%, with no differences according to the AHI.
<table-wrap id="Tab1"><label>Table 1</label>
<caption><p>Demographics and clinical features, lung function parameters, and sleep-related findings of the study population</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th rowspan="2">Variable</th>
<th>OSA</th>
<th>Controls</th>
<th rowspan="2"><italic>P</italic>
-value</th>
</tr>
<tr><th>(<italic>n</italic>
= 55)</th>
<th>(<italic>n</italic>
= 35)</th>
</tr>
</thead>
<tbody><tr><td>Age (years)</td>
<td>54.9 ± 8.8</td>
<td>50.2 ± 5.4</td>
<td>NS</td>
</tr>
<tr><td>Gender, male sex</td>
<td>39 (71)</td>
<td>24 (68)</td>
<td>NS</td>
</tr>
<tr><td colspan="4">Smoking habit</td>
</tr>
<tr><td> Smokers</td>
<td>9 (16)</td>
<td>0 (0)</td>
<td></td>
</tr>
<tr><td> Former smokers</td>
<td>23 (42)</td>
<td>0 (0)</td>
<td></td>
</tr>
<tr><td> No smokers</td>
<td>23 (42)</td>
<td>35 (100)</td>
<td></td>
</tr>
<tr><td> Pack/yr</td>
<td>32.8 ± 24.6</td>
<td></td>
<td></td>
</tr>
<tr><td> BMI (Kg/m<sup>2</sup>
)</td>
<td>32.9 ± 6.7</td>
<td>28.3 ± 4.7</td>
<td><bold>< 0.01</bold>
</td>
</tr>
<tr><td> Dyslipidemia (%)</td>
<td>10 (18)</td>
<td>0 (0)</td>
<td></td>
</tr>
<tr><td> Hypertension (%)</td>
<td>14 (25)</td>
<td>0 (0)</td>
<td></td>
</tr>
<tr><td> Diabetes (%)</td>
<td>12 (22)</td>
<td>0 (0)</td>
<td></td>
</tr>
<tr><td colspan="4"><bold>Lung function parameters</bold>
</td>
</tr>
<tr><td> FVC (%pred.)</td>
<td>85.4 ± 13.6</td>
<td>98 ± 12.5</td>
<td><bold>< 0.001</bold>
</td>
</tr>
<tr><td> FEV<sub>1</sub>
(%pred.)</td>
<td>87 ± 16.8</td>
<td>86 ± 13</td>
<td>NS</td>
</tr>
<tr><td> FEV<sub>1</sub>
/FVC (%)</td>
<td>102.7 ± 15.4</td>
<td>84 ± 9.5</td>
<td><bold>< 0.001</bold>
</td>
</tr>
<tr><td> TLC (% pred)</td>
<td>85 ± 5.9</td>
<td>86 ± 3.8</td>
<td>NS</td>
</tr>
<tr><td> DLCO<sub>sb</sub>
(% pred)</td>
<td>84.3 ± 16.1</td>
<td>86 ± 5</td>
<td>NS</td>
</tr>
<tr><td> pH</td>
<td>7.38 ± 0.3</td>
<td>7.39 ± 0.4</td>
<td>NS</td>
</tr>
<tr><td> PaO<sub>2</sub>
(mmHg)</td>
<td>84.7 ± 8.1</td>
<td>85.3 ± 6.2</td>
<td>NS</td>
</tr>
<tr><td> PaCO<sub>2</sub>
(mmHg)</td>
<td>39.8 ± 4.1</td>
<td>38.6 ± 4.5</td>
<td>NS</td>
</tr>
<tr><td> Lactates (mmol/L)</td>
<td>1.2 ± 1.4</td>
<td>1.1 ± 1.2</td>
<td>NS</td>
</tr>
<tr><td> HCO3<sup>−</sup>
(mmol/L)</td>
<td>26.1 ± 1.6</td>
<td>25.2 ± 1.4</td>
<td>NS</td>
</tr>
<tr><td> 6MWT mt</td>
<td>512.1 ± 175.1</td>
<td>568 ± 145.6</td>
<td>NS</td>
</tr>
<tr><td colspan="4"><bold>Sleep-related events</bold>
</td>
</tr>
<tr><td> TST (minutes)</td>
<td>358.4 ± 68.7</td>
<td>362 ± 64.5</td>
<td>NS</td>
</tr>
<tr><td> Supine time (%)</td>
<td>49.7 ± 33.8</td>
<td>41.2 ± 29.8</td>
<td>NS</td>
</tr>
<tr><td> AHI</td>
<td>46.3 ± 28.7</td>
<td>3.2 ± 1.2</td>
<td>< 0.0001</td>
</tr>
<tr><td> Supine AHI (events/hour)</td>
<td>41.4 ± 27</td>
<td>2.2 ± 2.4</td>
<td>< 0.0001</td>
</tr>
<tr><td> ODI</td>
<td>46 ± 30.7</td>
<td>3.3 ± 1.2</td>
<td>< 0.0001</td>
</tr>
<tr><td> t90 (%)</td>
<td>24 ± 22.2</td>
<td>0.4 ± 0.6</td>
<td>0.001</td>
</tr>
<tr><td> Nadir % SpO<sub>2</sub>
</td>
<td>68.5 ± 11.5</td>
<td>83.2 ± 6.2</td>
<td>0.0001</td>
</tr>
</tbody>
</table>
<table-wrap-foot><p>Data are expressed as absolute number (%) or mean ± SD. Statistically significant results (<italic>p</italic>
< 0.05) are reported in bold</p>
<p>Abbreviations: <italic>BMI</italic>
Body mass index, <italic>FVC</italic>
Forced vital capacity, <italic>FEV</italic>
<sub><italic>1</italic>
</sub>
Forced expiratory volume in the 1st second, <italic>TLC</italic>
Total lung capacity, <italic>DLCO</italic>
<sub><italic>sb</italic>
</sub>
Single breath carbon monoxide lung diffusing capacity, <italic>PaO</italic>
<sub><italic>2</italic>
</sub>
Oxygen arterial partial pressure, <italic>PaCO</italic>
<sub><italic>2</italic>
</sub>
Carbon dioxide arterial partial pressure, <italic>HCO3</italic>
Sodium bicarbonates, <italic>6MWT mt</italic>
, Meters traveled during 6 min walking test, <italic>TST</italic>
Total sleep time, <italic>AHI</italic>
Apnea/hypopnea index, <italic>ODI</italic>
Oxygen desaturation index, <italic>t90%</italic>
Percentage of time spent with SpO<sub>2</sub>
< 90%, <italic>SpO</italic>
<sub><italic>2</italic>
</sub>
Arterial oxygen saturation</p>
</table-wrap-foot>
</table-wrap>
<fig id="Fig1"><label>Fig. 1</label>
<caption><p>Levels of oxidative burst in OSA patients and healthy controls. <bold>a</bold>
Distribution of oxidative burst (OB), calculated as mean fluorescence intensity (MFI), in OSA patients with respect to healthy volunteers; <bold>b</bold>
Boxplot showing that peripheral levels of OB (MFI) are significantly increased in OSA patients as compared to healthy volunteers; <bold>c</bold>
Boxplot showing the distribution of OB (MFI) in OSA patients according to t90%. As reported, OB levels are significantly increased in patients with t90 > 30%</p>
</caption>
<graphic xlink:href="12890_2020_1099_Fig1_HTML" id="MO1"></graphic>
</fig>
</p>
</sec>
<sec id="Sec11"><title>LV systolic function is impaired at rest and at peak exercise in moderate-severe OSA with a good reproducibility of 2DSTE measurements</title>
<p id="Par42">LVEF was similar in OSA and control cohorts, and preserved in both (Table <xref rid="Tab2" ref-type="table">2</xref>
). LV mass was mildly increased in OSA with no significant difference in LV diameters in the 2 groups (Table <xref rid="Tab2" ref-type="table">2</xref>
). LV speckle tracking was obtainable at rest in 95% of the total analysed segments. The remaining 5% segments were not considered due to a suboptimal tracking score. In OSA patients, LV GLS was significantly reduced at rest, this variation being statistically meaningful in all segments analysed (Table <xref rid="Tab2" ref-type="table">2</xref>
, Fig. <xref rid="Fig2" ref-type="fig">2</xref>
). Also LV GLS increase upon exercise was lower as compared to controls (Table <xref rid="Tab3" ref-type="table">3</xref>
).
<table-wrap id="Tab2"><label>Table 2</label>
<caption><p>Left ventricle standard echo and 2D speckle tracking echo measurements at rest and peak effort</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th rowspan="2">Variable</th>
<th>OSA</th>
<th>Controls</th>
<th rowspan="2"><italic>P</italic>
-value</th>
</tr>
<tr><th>(<italic>n</italic>
= 55)</th>
<th>(<italic>n</italic>
= 35)</th>
</tr>
</thead>
<tbody><tr><td colspan="4"><bold>Resting measurements</bold>
</td>
</tr>
<tr><td> SpO<sub>2</sub>
(%)</td>
<td>94.7 ± 16.2</td>
<td>98 ± 1.6</td>
<td><bold>< 0.01</bold>
</td>
</tr>
<tr><td> IVSd (mm)</td>
<td>11.4 ± 1.8</td>
<td>9.1 ± 2.3</td>
<td><bold>< 0.01</bold>
</td>
</tr>
<tr><td> PWd (mm)</td>
<td>10.4 ± 1.6</td>
<td>8.7 ± 2.1</td>
<td><bold>< 0.01</bold>
</td>
</tr>
<tr><td> LVEDD (mm)</td>
<td>48.3 ± 3.9</td>
<td>47.2 ± 4.4</td>
<td>NS</td>
</tr>
<tr><td> LVESD (mm)</td>
<td>34.3 ± 3.6</td>
<td>32.4 ± 4.1</td>
<td>NS</td>
</tr>
<tr><td> LV mass index (g/m<sup>2</sup>
)</td>
<td>52.8 ± 5.3</td>
<td>48.1 ± 3.4</td>
<td><bold>< 0.01</bold>
</td>
</tr>
<tr><td> Biplane LVEF (%)</td>
<td>56.5 ± 6.2</td>
<td>57.4 ± 5.5</td>
<td>NS</td>
</tr>
<tr><td> LV GLS (%)</td>
<td>−13.4 ± 3.8</td>
<td>−18.4 ± 3.3</td>
<td><bold>< 0.001</bold>
</td>
</tr>
<tr><td> Mitral E velocity (cm/s)</td>
<td>0.9 ± 0.3</td>
<td>0.8 ± 0.4</td>
<td>NS</td>
</tr>
<tr><td> Mitral A velocity (cm/s)</td>
<td>0.7 ± 0.4</td>
<td>0.9 ± 0.3</td>
<td>NS</td>
</tr>
<tr><td> E/A ratio</td>
<td>1.2 ± 0.4</td>
<td>0.9 ± 0.4</td>
<td><bold>< 0.01</bold>
</td>
</tr>
<tr><td> Mitral septal e’ velocity (cm/s)</td>
<td>0.13 ± 0.02</td>
<td>0.16 ± 0.05</td>
<td><bold>< 0.01</bold>
</td>
</tr>
<tr><td> Mitrallateral e’ velocity (cm/s)</td>
<td>0.14 ± 0.03</td>
<td>0.17 ± 0.03</td>
<td><bold>< 0.01</bold>
</td>
</tr>
<tr><td> E/e’ ratio</td>
<td>8.2 ± 3.1</td>
<td>5.9 ± 2.8</td>
<td><bold>< 0.01</bold>
</td>
</tr>
<tr><td> LAVI (ml/m<sup>2</sup>
)</td>
<td>32.4 ± 4.4</td>
<td>28.3 ± 5.1</td>
<td><bold>< 0.01</bold>
</td>
</tr>
<tr><td> sPAP (mmHg)</td>
<td>31.5 ± 7.8</td>
<td>21.3 ± 2.9</td>
<td><bold>< 0.01</bold>
</td>
</tr>
<tr><td> TAPSE (mm)</td>
<td>22.5 ± 3.3</td>
<td>24.5 ± 3.8</td>
<td>NS</td>
</tr>
<tr><td> Tricuspid S′ velocity (cm/s)</td>
<td>13.3 ± 2.2</td>
<td>14.4 ± 3.1</td>
<td>NS</td>
</tr>
<tr><td colspan="4"><bold>Peak effort measurements</bold>
</td>
</tr>
<tr><td> SpO<sub>2</sub>
(%)</td>
<td>92.3 ± 3.2</td>
<td>97.2 ± 2.6</td>
<td><bold>< 0.01</bold>
</td>
</tr>
<tr><td> Exercise capacity (Watt)</td>
<td>115.3 ± 25</td>
<td>150.4 ± 35</td>
<td><bold>< 0.001</bold>
</td>
</tr>
<tr><td> Biplane LVEF (%)</td>
<td>62.3 ± 5.8</td>
<td>65.7 ± 6.8</td>
<td>NS</td>
</tr>
<tr><td> LV GLS (%)</td>
<td>−15.8 ± 2.6</td>
<td>−23.4 ± 4.3</td>
<td><bold>< 0.001</bold>
</td>
</tr>
<tr><td> Mitral E velocity (cm/s)</td>
<td>1.1 ± 0.5</td>
<td>1.2 ± 0.6</td>
<td>NS</td>
</tr>
<tr><td> Mitral A velocity (cm/s)</td>
<td>0.9 ± 0.4</td>
<td>0.9 ± 0.3</td>
<td>NS</td>
</tr>
<tr><td> E/A ratio</td>
<td>1.2 ± 0.4</td>
<td>1.3 ± 0.5</td>
<td><bold>< 0.01</bold>
</td>
</tr>
<tr><td> Mitral septal e’ velocity (cm/s)</td>
<td>0.08 ± 0.02</td>
<td>0.18 ± 0.05</td>
<td><bold>< 0.0001</bold>
</td>
</tr>
<tr><td> Mitral lateral e’ velocity (cm/s)</td>
<td>0.07 ± 0.03</td>
<td>0.19 ± 0.03</td>
<td><bold>< 0.0001</bold>
</td>
</tr>
<tr><td> E/e’ ratio</td>
<td>15.4 ± 4.1</td>
<td>7.4 ± 2.8</td>
<td><bold>< 0.0001</bold>
</td>
</tr>
<tr><td> sPAP (mmHg)</td>
<td>45.5 ± 5.8</td>
<td>28.4 ± 4.2</td>
<td><bold>< 0.001</bold>
</td>
</tr>
<tr><td> TAPSE (mm)</td>
<td>26.4 ± 2.3</td>
<td>27.5 ± 5.8</td>
<td>NS</td>
</tr>
<tr><td> Tricuspid s’ velocity (cm/s)</td>
<td>16.4 ± 3.1</td>
<td>17.7 ± 4.1</td>
<td>NS</td>
</tr>
</tbody>
</table>
<table-wrap-foot><p>Data are expressed as mean ± SD. Statistically significant results (<italic>p</italic>
< 0.05) are reported in bold</p>
<p>Abbreviations<italic>: SpO</italic>
<sub><italic>2</italic>
</sub>
Arterial oxygen saturation, <italic>IVSd</italic>
Inter-ventricular septum thickness at end diastole, <italic>PWd</italic>
Posterior wall thickness at end diastole, <italic>LVEDD</italic>
Left ventricular end diastolic diameter, <italic>LVESD</italic>
Left ventricular end systolic diameter, <italic>LV</italic>
Left ventricle, <italic>LVEF</italic>
Left ventricular ejection fraction, <italic>LV GLS</italic>
Left ventricular global longitudinal strain, <italic>LAVI</italic>
Left atrial volume index, <italic>sPAP</italic>
Systolic pulmonary artery pressure, <italic>TAPSE</italic>
Tricuspid annular plane systolic excursion</p>
</table-wrap-foot>
</table-wrap>
<fig id="Fig2"><label>Fig. 2</label>
<caption><p>Left ventricular systolic and diastolic dysfunction in OSA patients. Two-dimensional echocardiography (<bold>a</bold>
: apical four chamber view) showing mild impairment of resting LV regional and global strain (mainly in the septal region, see arrow) (<bold>b</bold>
) and significant diastolic dysfunction assessed by transmitral flow pattern (<bold>c</bold>
) and both lateral (<bold>d</bold>
) and septal (<bold>e</bold>
) pulsed Doppler tissue imaging</p>
</caption>
<graphic xlink:href="12890_2020_1099_Fig2_HTML" id="MO2"></graphic>
</fig>
<table-wrap id="Tab3"><label>Table 3</label>
<caption><p>Changes in echocardiographic parameters and oxygen saturation in OSA and controls during effort</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th rowspan="2">Variable</th>
<th>OSA</th>
<th>Controls</th>
<th rowspan="2"><italic>P</italic>
-value</th>
</tr>
<tr><th>(<italic>n</italic>
= 55)</th>
<th>(<italic>n</italic>
= 35)</th>
</tr>
</thead>
<tbody><tr><td>Δ sPAP (%)</td>
<td>44.3 ± 6.4</td>
<td>32.3 ± 5.5</td>
<td><bold>< 0.001</bold>
</td>
</tr>
<tr><td>Δ E/e’ ratio (%)</td>
<td>87.5 ± 3.5</td>
<td>25.4 ± 3.3</td>
<td><bold>< 0.0001</bold>
</td>
</tr>
<tr><td>Δ LV GLS (%)</td>
<td>15.8 ± 3.4</td>
<td>25.4 ± 4.1</td>
<td><bold>< 0.001</bold>
</td>
</tr>
<tr><td>Δ SpO<sub>2</sub>
(%)</td>
<td>- 2.5 ± 3.3</td>
<td>−0.8 ± 2.8</td>
<td><bold>< 0.01</bold>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot><p>Data are expressed as mean ± SD. Statistically significant results (<italic>p</italic>
< 0.05) are reported in bold</p>
<p>Abbreviations<italic>: sPAP</italic>
Systolic pulmonary artery pressure, <italic>LV GLS</italic>
Left ventricular global longitudinal strain, <italic>SpO</italic>
<sub><italic>2</italic>
</sub>
Arterial oxygen saturation</p>
</table-wrap-foot>
</table-wrap>
</p>
<p id="Par43">Overall, we observed a good reproducibility of global LV strain measurements in our study population, similar to that reported for speckle-tracking-based strain measures performed in selected samples – including healthy young adults [<xref ref-type="bibr" rid="CR20">20</xref>
, <xref ref-type="bibr" rid="CR21">21</xref>
]. The average coefficients of variation were ≤ 7% for the longitudinal strain measures. For all analyzed measures, intra- and intra-observer ICC values were ≥ 0.80 <bold>(</bold>
Intra-observer variability: COV: LV GLS: 5.37 (ICC 0.73); Bland-Altman analysis: LV GLS (95% CI ± 1.5; percent error 3.2%). Inter-observer variability: COV: LV GLS: 7.22 (ICC 0.77); Bland-Altman analysis: LV GLS (95% CI ±1.7; percent error 3.6%).</p>
</sec>
<sec id="Sec12"><title>LV diastolic function is impaired at rest and at peak exercise in moderate-severe OSA</title>
<p id="Par44">E/e’ ratio, sPAP and LAVI at rest were all significantly higher in patients affected by OSA as compared to healthy controls; moreover, both septal and lateral e’ velocities were significantly lower in the former (Table <xref rid="Tab2" ref-type="table">2</xref>
, Fig. <xref rid="Fig2" ref-type="fig">2</xref>
). According to recent guidelines, a definite diastolic dysfunction was present at rest in 19 OSA (34.5%) [<xref ref-type="bibr" rid="CR22">22</xref>
].</p>
<p id="Par45">E/e’ increase during exertion was significantly higher in patients affected by OSA when compared to controls; sPAP increase (difference between peak exertion and resting sPAP) also showed the same trend along with a three-fold decrease of oxygen saturation (Table <xref rid="Tab3" ref-type="table">3</xref>
).</p>
</sec>
<sec id="Sec13"><title>Exercise tolerance is reduced in moderate-severe OSA</title>
<p id="Par46">During physical exercise, OSA patients showed a reduced tolerance with a lower maximal workload in Watts (115.3 ± 25 vs 150.4 ± 35, <italic>p</italic>
< 0.001) and oxygen saturation level (92.3% ± 3.2 vs 97.2% ± 2.6, <italic>p</italic>
< 0.01) as compared to healthy controls (Table <xref rid="Tab2" ref-type="table">2</xref>
).</p>
</sec>
<sec id="Sec14"><title>Resting and exercise-induced LV diastolic dysfunction is associated with OSA severity but not with OB levels</title>
<p id="Par47">Logistic regression analysis showed that arterial hypertension (OR 2.67, 95% CI 1.74–5.61; <italic>p</italic>
< 0.01), resting LV GLS > − 15% (OR 3.3, 95% CI 2.34–4.15; <italic>p</italic>
< 0.001) and severe AHI (OR 2.96, 95% CI 1.92–4.91; <italic>p</italic>
< 0.001) were independently associated with LV diastolic dysfunction at rest.</p>
<p id="Par48">At peak exercise, by linear regression analysis E/e’ ratio was directly related to peak exertion capacity expressed in Watts (beta coefficient − 0.50, <italic>p</italic>
< 0.001), to blood lactates at rest (beta coefficient 0.36, <italic>p</italic>
< 0.01), to resting LV GLS (beta coefficient 0.46, <italic>p</italic>
< 0.001), and to the AHI (beta coefficient 0.42, <italic>p</italic>
< 0.001) (Table <xref rid="Tab4" ref-type="table">4</xref>
). No significant correlations were found with OB, BMI smoking, and co-morbidities.
<table-wrap id="Tab4"><label>Table 4</label>
<caption><p>Multivariate analysis model: correlation between E/e’ ratio at peak exercise with univariable clinical parameters</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th colspan="2">Variable</th>
<th>Beta coefficient</th>
<th><italic>P</italic>
-value</th>
</tr>
</thead>
<tbody><tr><td rowspan="4"><bold>LV E/e’ at peak exercise</bold>
</td>
<td><bold>Watts (at peak effort)</bold>
</td>
<td>− 0.50</td>
<td><bold>< 0.001</bold>
</td>
</tr>
<tr><td><bold>Blood lactates (at rest)</bold>
</td>
<td>0.36</td>
<td><bold>< 0.01</bold>
</td>
</tr>
<tr><td><bold>LV GLS (at rest)</bold>
</td>
<td>0.46</td>
<td><bold>< 0.001</bold>
</td>
</tr>
<tr><td><bold>AHI</bold>
</td>
<td>0.42</td>
<td><bold>< 0.001</bold>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot><p>Statistically significant results (<italic>p</italic>
< 0.05) are reported in bold</p>
<p>Abbreviations: <italic>LV GLS</italic>
Left ventricular global longitudinal strain, <italic>AHI</italic>
Apnea-hypopnea index</p>
</table-wrap-foot>
</table-wrap>
</p>
</sec>
</sec>
<sec id="Sec15"><title>Discussion</title>
<p id="Par49">OSA is frequently associated with adverse clinical outcomes [<xref ref-type="bibr" rid="CR1">1</xref>
], including cardiovascular diseases [<xref ref-type="bibr" rid="CR24">24</xref>
–<xref ref-type="bibr" rid="CR27">27</xref>
]. In the present study, we showed that OSA patients: (1) have subclinical LV systolic dysfunction despite a preserved LV output, and a low contractile reserve as compared to healthy controls; (2) have an impaired LV diastolic reserve along with a reduced exercise tolerance; (3) display higher levels of OB that are not correlated with diastolic heart function.</p>
<p id="Par50">In 2007, Gondi et al. reported that OSA was associated with sleep-induced LV systolic longitudinal dysfunction, as measured by pulsed wave Doppler and tissue Doppler imaging (TDI) [<xref ref-type="bibr" rid="CR28">28</xref>
]. As TDI is technically limited by the insonation angle of the ultrasound beam, we further proved by 2DSTE, which is independent of the interrogation angle, that LV and RV early myocardial dysfunction occur in OSA patients and are associated with disease severity [<xref ref-type="bibr" rid="CR29">29</xref>
]. The relationship between OSA and LV systolic dysfunction is not surprising as OSA patients experience repeated increases in LV after-load during sleep, due to exaggerated negative intra-thoracic pressure and intermittent hypoxia and arousals. Acute repeated increases in after-load can therefore result in LV subclinical systolic dysfunction [<xref ref-type="bibr" rid="CR29">29</xref>
]. In this study, we enrolled patients with moderate-severe OSA and healthy controls with preserved LVEF and found an early involvement of the LV myocardium in the former. Actually, despite LVEF, that is traditionally used as systolic function parameter, was normal in OSA patients, we found an impaired basal LV GLS, which is expression of subclinical LV pump dysfunction. In addition, we also found that strain increase during physical exercise in OSA patients was lower if compared to healthy controls, reflecting their low contractile reserve. Interestingly, we previously detected that OSA patients have also a subclinical RV dysfunction, and that RV GLS impairment was associated with sPAP and disease severity [<xref ref-type="bibr" rid="CR30">30</xref>
].</p>
<p id="Par51">Previous studies show that the prevalence of LV diastolic dysfunction at rest among OSA patients varies from 23 to 56%, depending on the sample size and the method of diastolic function assessment [<xref ref-type="bibr" rid="CR31">31</xref>
–<xref ref-type="bibr" rid="CR34">34</xref>
]. In our cohort we observed that, according to recent guidelines [<xref ref-type="bibr" rid="CR22">22</xref>
], a definite diastolic dysfunction was present in the 34.5% of OSA patients at rest. Pathophysiological mechanisms underlying LV diastolic dysfunction in OSA have been widely studied: repetitive hypoxemia/re-oxygenation sequences, sympathetic bursts, renin-angiotensin-aldosterone system activation, oxidative stress, systemic inflammation, intra-thoracic pressure reduction and trans-mural pressure increasing, all participate in the development of LV hypertrophy and remodelling, and hence of LV diastolic dysfunction [<xref ref-type="bibr" rid="CR5">5</xref>
–<xref ref-type="bibr" rid="CR8">8</xref>
].</p>
<p id="Par52">To our knowledge this is the first study addressing the LV diastolic performance both at rest and at peak exercise in a selected population of OSA patients. In middle-aged healthy subjects, the E/e′ ratio does not change significantly with exercise because of proportional increases in both the mitral inflow and annular velocities [<xref ref-type="bibr" rid="CR35">35</xref>
–<xref ref-type="bibr" rid="CR38">38</xref>
]. Conversely, in our series almost all patients enrolled showed an increase of the E/e’ ratio, that was significantly higher than in the control group. This finding indicates an impairment of the LV diastolic function reserve resulting in an increased LV filling pressure during exercise [<xref ref-type="bibr" rid="CR22">22</xref>
, <xref ref-type="bibr" rid="CR39">39</xref>
, <xref ref-type="bibr" rid="CR40">40</xref>
]. In agreement with these observations, also sPAP increase was significantly higher in OSA than in healthy subjects. The mean sPAP value in OSA patients was > 43 mmHg (as estimated by a TRV > 3.1 m/s), which is the echocardiography threshold of abnormal diastolic stress according to international guidelines [<xref ref-type="bibr" rid="CR23">23</xref>
]. The present study clearly underlines the strong relation between E/e’ ratio and exercise tolerance in OSA. Patients with a higher E/e’ ratio at peak exercise, and hence a more impaired diastolic reserve, showed a reduced functional capacity highlighted by a lower maximal workload and a reduced peak SpO<sub>2</sub>
level. The E/e’ ratio at peak exercise also resulted significantly correlated to LV GLS, to AHI, which reflects OSA severity, and to blood lactates, which are suggestive of inadequate tissue perfusion. These findings can be explained by the mentioned pathological mechanisms responsible for myocardial remodelling and fibrosis. The latter provokes impairment in both systolic and diastolic function, which can worsen during exercise, leading to reduced functional capacity.</p>
<p id="Par53">Our study has some limitations. First, it is a single-centre study with a sample size too small to drive definitive general conclusions concerning subclinical LV functional impairment in OSA patients. Also, our findings cannot necessarily be extrapolated to patients with mild disease. Finally, despite we found no correlations between the diastolic impairment during exercise and patients age, OB, BMI, smoking and co-morbidities, we cannot definitely exclude their contribution. Indeed, while we excluded OSA patients with major heart and lung diseases, the prevalence of cardiovascular risk factors, such as smoke, obesity, dyslipidemia, diabetes, and hypertension, was still not negligible in our patient cohort. Further studies in larger populations will certainly help to address their impact by ad hoc sub-group analyses.</p>
</sec>
<sec id="Sec16"><title>Conclusions</title>
<p id="Par54">In conclusion, evaluation of diastolic function and myocardial deformation during exercise is feasible through stress echocardiography and provides valuable information in predicting exercise capacity in a selected population of moderate-severe OSA patients with preserved LVEF. These patients show subclinical LV systolic dysfunction, impaired LV systolic and diastolic reserve, reduced exercise tolerance, and increased peripheral levels of OB. A CPAP treatment and a therapy aimed at increasing LV diastolic function reserve might improve the quality of life and exercise tolerability in this target population.</p>
</sec>
</body>
<back><glossary><title>Abbreviations</title>
<def-list><def-item><term>2DSTE</term>
<def><p id="Par5">2D speckle tracking echocardiography</p>
</def>
</def-item>
<def-item><term>6-MWT</term>
<def><p id="Par6">6-min walk test</p>
</def>
</def-item>
<def-item><term>A</term>
<def><p id="Par7">Late diastolic velocity of the mitral inflow</p>
</def>
</def-item>
<def-item><term>AHI</term>
<def><p id="Par8">Apnea/hypopnea index</p>
</def>
</def-item>
<def-item><term>BSA</term>
<def><p id="Par9">Body surface area</p>
</def>
</def-item>
<def-item><term>CPAP</term>
<def><p id="Par10">Continuous positive airway pressure (CPAP)</p>
</def>
</def-item>
<def-item><term>DHR</term>
<def><p id="Par11">Dihydrorhodamine</p>
</def>
</def-item>
<def-item><term>DLCO<sub>sb</sub>
</term>
<def><p id="Par12">Single-breath diffusing lung capacity of the carbon monoxide</p>
</def>
</def-item>
<def-item><term>E</term>
<def><p id="Par13">Early diastolic velocity of the mitral inflow</p>
</def>
</def-item>
<def-item><term>e’</term>
<def><p id="Par14">Early myocardial diastolic velocity</p>
</def>
</def-item>
<def-item><term>EF</term>
<def><p id="Par15">Ejection fraction</p>
</def>
</def-item>
<def-item><term>GLS</term>
<def><p id="Par16">Global longitudinal strain</p>
</def>
</def-item>
<def-item><term>LAVI</term>
<def><p id="Par17">Left atrial volume index</p>
</def>
</def-item>
<def-item><term>LV</term>
<def><p id="Par18">Left ventricular</p>
</def>
</def-item>
<def-item><term>NRF</term>
<def><p id="Par19">Nocturnal respiratory failure</p>
</def>
</def-item>
<def-item><term>OB</term>
<def><p id="Par20">Oxidative burst</p>
</def>
</def-item>
<def-item><term>OSA</term>
<def><p id="Par21">Obstructive sleep apnea</p>
</def>
</def-item>
<def-item><term>PW</term>
<def><p id="Par22">Pulsed wave</p>
</def>
</def-item>
<def-item><term>RAP</term>
<def><p id="Par23">Right atrial pressure</p>
</def>
</def-item>
<def-item><term>ROC</term>
<def><p id="Par24">Receiver operating characteristic</p>
</def>
</def-item>
<def-item><term>ROS</term>
<def><p id="Par25">Reactive oxygen species</p>
</def>
</def-item>
<def-item><term>RV</term>
<def><p id="Par26">Right ventricular</p>
</def>
</def-item>
<def-item><term>sPAP</term>
<def><p id="Par27">Systolic pulmonary artery pressure</p>
</def>
</def-item>
<def-item><term>SpO<sub>2</sub>
</term>
<def><p id="Par28">Oxygen saturation</p>
</def>
</def-item>
<def-item><term>TDI</term>
<def><p id="Par29">Tissue Doppler imaging</p>
</def>
</def-item>
<def-item><term>TRV</term>
<def><p id="Par30">Tricuspid regurgitation velocity</p>
</def>
</def-item>
</def-list>
</glossary>
<fn-group><fn><p><bold>Publisher’s Note</bold>
</p>
<p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p>
</fn>
<fn><p>Antonello D’Andrea and Angelo Canora contributed equally to this work.</p>
</fn>
<fn><p>This study is dedicated to the memory of Prof. Maurizio Galderisi, prematurely passed away because of COVID-19.</p>
</fn>
</fn-group>
<ack><p>The present work has been presented as abstract at the 80th SIC National Italian Congress 2019 (European heart Journal Supplements 2019; 21: Supplement J- The Heart of the matter; J73-N1).</p>
</ack>
<notes notes-type="author-contribution"><title>Authors’ contributions</title>
<p>ADA and AC equally contributed. ADA, AC and MB: conception and design of the study, data acquisition and analysis, and manuscript writing. SS MG and PL: echocardiography data acquisition and analysis. DG and SZ: flow cytometry data acquisition and analysis. GEP, CN, GG, AS: patients recruitment. All Authors approved the final version of the manuscript.</p>
</notes>
<notes notes-type="funding-information"><title>Funding</title>
<p>No funding.</p>
</notes>
<notes notes-type="data-availability"><title>Availability of data and materials</title>
<p>The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.</p>
</notes>
<notes><title>Ethics approval and consent to participate</title>
<p id="Par55">The study was conducted in accordance with the amended Declaration of Helsinki. The “Federico II” Istitutional Ethical Committee, Naples, Italy approved the study (Protocol 1129, 4 August 2015) and all individuals gave written informed consent.</p>
</notes>
<notes><title>Consent for publication</title>
<p id="Par56">Not applicable</p>
</notes>
<notes notes-type="COI-statement"><title>Competing interests</title>
<p id="Par57">Prof. M. Bocchino and Prof A. Sanduzzi are associate editors of BMC Pulm Med. The remaining Authors have no conflicting interests for this study.</p>
</notes>
<ref-list id="Bib1"><title>References</title>
<ref id="CR1"><label>1.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Qaseem</surname>
<given-names>A</given-names>
</name>
<name><surname>Dallas</surname>
<given-names>P</given-names>
</name>
<name><surname>Owens</surname>
<given-names>DK</given-names>
</name>
<name><surname>Starkey</surname>
<given-names>M</given-names>
</name>
<name><surname>Holty</surname>
<given-names>JEC</given-names>
</name>
<name><surname>Shekelle</surname>
<given-names>P</given-names>
</name>
</person-group>
<article-title>Diagnosis of obstructive sleep apnea in adults: a clinical practice guideline from the American College of Physicians</article-title>
<source>Ann Intern Med</source>
<year>2014</year>
<volume>161</volume>
<issue>3</issue>
<fpage>210</fpage>
<lpage>220</lpage>
<pub-id pub-id-type="doi">10.7326/M12-3187</pub-id>
<pub-id pub-id-type="pmid">25089864</pub-id>
</element-citation>
</ref>
<ref id="CR2"><label>2.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Phillips</surname>
<given-names>B</given-names>
</name>
</person-group>
<article-title>Sleep-disordered breathing and cardiovascular disease</article-title>
<source>Sleep Med Rev</source>
<year>2005</year>
<volume>9</volume>
<issue>2</issue>
<fpage>131</fpage>
<lpage>140</lpage>
<pub-id pub-id-type="doi">10.1016/j.smrv.2004.09.007</pub-id>
<pub-id pub-id-type="pmid">15737791</pub-id>
</element-citation>
</ref>
<ref id="CR3"><label>3.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Leung</surname>
<given-names>RST</given-names>
</name>
<name><surname>Bradley</surname>
<given-names>TD</given-names>
</name>
</person-group>
<article-title>State of the art sleep apnea and cardiovascular disease</article-title>
<source>Am J Respir Crit Care Med</source>
<year>2001</year>
<volume>164</volume>
<issue>12</issue>
<fpage>2147</fpage>
<lpage>2165</lpage>
<pub-id pub-id-type="doi">10.1164/ajrccm.164.12.2107045</pub-id>
<pub-id pub-id-type="pmid">11751180</pub-id>
</element-citation>
</ref>
<ref id="CR4"><label>4.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Haruki</surname>
<given-names>N</given-names>
</name>
<name><surname>Takeuchi</surname>
<given-names>M</given-names>
</name>
<name><surname>Kanazawa</surname>
<given-names>Y</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Continuous positive airway pressure ameliorates sleep-induced subclinical left ventricular systolic dysfunction: demonstration by two-dimensional speckle-tracking echocardiography</article-title>
<source>Eur J Echocardiogr</source>
<year>2010</year>
<volume>11</volume>
<issue>4</issue>
<fpage>352</fpage>
<lpage>358</lpage>
<pub-id pub-id-type="doi">10.1093/ejechocard/jep215</pub-id>
<pub-id pub-id-type="pmid">20123859</pub-id>
</element-citation>
</ref>
<ref id="CR5"><label>5.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bodez</surname>
<given-names>D</given-names>
</name>
<name><surname>Damy</surname>
<given-names>T</given-names>
</name>
<name><surname>Soulat-Dufour</surname>
<given-names>L</given-names>
</name>
<name><surname>Meuleman</surname>
<given-names>C</given-names>
</name>
<name><surname>Cohen</surname>
<given-names>A</given-names>
</name>
</person-group>
<article-title>Consequences of obstructive sleep apnoea syndrome on left ventricular geometry and diastolic function</article-title>
<source>Arch Cardiovasc Dis</source>
<year>2016</year>
<volume>109</volume>
<issue>8–9</issue>
<fpage>494</fpage>
<lpage>503</lpage>
<pub-id pub-id-type="doi">10.1016/j.acvd.2016.02.011</pub-id>
<pub-id pub-id-type="pmid">27344377</pub-id>
</element-citation>
</ref>
<ref id="CR6"><label>6.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shim</surname>
<given-names>CY</given-names>
</name>
<name><surname>Kim</surname>
<given-names>D</given-names>
</name>
<name><surname>Park</surname>
<given-names>S</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Effects of continuous positive airway pressure therapy on left ventricular diastolic function: a randomised, sham-controlled clinical trial</article-title>
<source>Eur Respir J</source>
<year>2018</year>
<volume>51</volume>
<fpage>1701774</fpage>
<pub-id pub-id-type="doi">10.1183/13993003.01774-2017</pub-id>
<pub-id pub-id-type="pmid">29386335</pub-id>
</element-citation>
</ref>
<ref id="CR7"><label>7.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cetin</surname>
<given-names>S</given-names>
</name>
<name><surname>Vural</surname>
<given-names>M</given-names>
</name>
<name><surname>Akdemir</surname>
<given-names>R</given-names>
</name>
<name><surname>Firat</surname>
<given-names>H</given-names>
</name>
</person-group>
<article-title>Left atrial remodelling may predict exercise capacity in obstructive sleep apnoea patients</article-title>
<source>Acta Cardiol</source>
<year>2018</year>
<volume>73</volume>
<issue>5</issue>
<fpage>471</fpage>
<lpage>478</lpage>
<pub-id pub-id-type="doi">10.1080/00015385.2017.1414730</pub-id>
<pub-id pub-id-type="pmid">29235925</pub-id>
</element-citation>
</ref>
<ref id="CR8"><label>8.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Butt</surname>
<given-names>M</given-names>
</name>
<name><surname>Dwivedi</surname>
<given-names>G</given-names>
</name>
<name><surname>Shantsila</surname>
<given-names>A</given-names>
</name>
<name><surname>Khair</surname>
<given-names>OA</given-names>
</name>
<name><surname>Lip</surname>
<given-names>GYH</given-names>
</name>
</person-group>
<article-title>Left ventricular systolic and diastolic function in obstructive sleep apnea impact of continuous positive airway pressure therapy</article-title>
<source>Circ Heart Fail</source>
<year>2012</year>
<volume>5</volume>
<issue>2</issue>
<fpage>226</fpage>
<lpage>223</lpage>
<pub-id pub-id-type="doi">10.1161/CIRCHEARTFAILURE.111.964106</pub-id>
<pub-id pub-id-type="pmid">22414938</pub-id>
</element-citation>
</ref>
<ref id="CR9"><label>9.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lira</surname>
<given-names>AB</given-names>
</name>
<name><surname>de Sousa Rodrigues</surname>
<given-names>CF</given-names>
</name>
</person-group>
<article-title>Evaluation of oxidative stress markers in obstructive sleep apnea syndrome and additional antioxidant therapy: a review article</article-title>
<source>Sleep Breath</source>
<year>2016</year>
<volume>20</volume>
<fpage>1155</fpage>
<lpage>1160</lpage>
<pub-id pub-id-type="doi">10.1007/s11325-016-1367-3</pub-id>
<pub-id pub-id-type="pmid">27255237</pub-id>
</element-citation>
</ref>
<ref id="CR10"><label>10.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Passali</surname>
<given-names>D</given-names>
</name>
<name><surname>Corallo</surname>
<given-names>G</given-names>
</name>
<name><surname>Yaremchuk</surname>
<given-names>S</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Oxidative stress in patients with obstructive sleep apnoea syndrome</article-title>
<source>Acta Otorhinolaryngol Ital</source>
<year>2015</year>
<volume>35</volume>
<issue>6</issue>
<fpage>420</fpage>
<lpage>425</lpage>
<pub-id pub-id-type="pmid">26900248</pub-id>
</element-citation>
</ref>
<ref id="CR11"><label>11.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hopps</surname>
<given-names>E</given-names>
</name>
<name><surname>Lo Presti</surname>
<given-names>R</given-names>
</name>
<name><surname>Montana</surname>
<given-names>M</given-names>
</name>
<name><surname>Canino</surname>
<given-names>B</given-names>
</name>
<name><surname>Calandrino</surname>
<given-names>V</given-names>
</name>
<name><surname>Caimi</surname>
<given-names>G</given-names>
</name>
</person-group>
<article-title>Analysis of the correlations between oxidative stress, gelatinases and their tissue inhibitors in the human subjects with obstructive sleep apnea syndrome</article-title>
<source>J Physiol Pharmacol</source>
<year>2015</year>
<volume>66</volume>
<issue>6</issue>
<fpage>803</fpage>
<lpage>810</lpage>
<pub-id pub-id-type="pmid">26769829</pub-id>
</element-citation>
</ref>
<ref id="CR12"><label>12.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Asker</surname>
<given-names>S</given-names>
</name>
<name><surname>Asker</surname>
<given-names>M</given-names>
</name>
<name><surname>Sarikaya</surname>
<given-names>E</given-names>
</name>
<name><surname>Sunnetcioglu</surname>
<given-names>A</given-names>
</name>
<name><surname>Aslan</surname>
<given-names>M</given-names>
</name>
<name><surname>Demir</surname>
<given-names>H</given-names>
</name>
</person-group>
<article-title>Oxidative stress parameters and their correlation with clinical, metabolic and polysomnographic parameters in severe obstructive sleep apnea syndrome</article-title>
<source>Int J Clin Exp Med</source>
<year>2015</year>
<volume>8</volume>
<issue>7</issue>
<fpage>11449</fpage>
<lpage>11455</lpage>
<pub-id pub-id-type="pmid">26379962</pub-id>
</element-citation>
</ref>
<ref id="CR13"><label>13.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Berry</surname>
<given-names>RB</given-names>
</name>
<name><surname>Budhiraja</surname>
<given-names>R</given-names>
</name>
<name><surname>Gottlieb</surname>
<given-names>DJ</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Rules for scoring respiratory events in sleep: update of the 2007 AASM manual for the scoring of sleep and associated events</article-title>
<source>J Clin Sleep Med</source>
<year>2012</year>
<volume>8</volume>
<issue>5</issue>
<fpage>597</fpage>
<lpage>619</lpage>
<pub-id pub-id-type="doi">10.5664/jcsm.2172</pub-id>
<pub-id pub-id-type="pmid">23066376</pub-id>
</element-citation>
</ref>
<ref id="CR14"><label>14.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Levi-Valensi</surname>
<given-names>P</given-names>
</name>
<name><surname>Weitzenblum</surname>
<given-names>E</given-names>
</name>
<name><surname>Rida</surname>
<given-names>Z</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Sleep-related oxygen desaturation and daytime pulmonary haemodynamics in COPD patients</article-title>
<source>Eur Respir J</source>
<year>1992</year>
<volume>5</volume>
<issue>3</issue>
<fpage>301</fpage>
<lpage>307</lpage>
<pub-id pub-id-type="pmid">1572442</pub-id>
</element-citation>
</ref>
<ref id="CR15"><label>15.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fletcher</surname>
<given-names>EC</given-names>
</name>
<name><surname>Miller</surname>
<given-names>J</given-names>
</name>
<name><surname>Divine</surname>
<given-names>GW</given-names>
</name>
<name><surname>Fletcher</surname>
<given-names>JG</given-names>
</name>
<name><surname>Miller</surname>
<given-names>T</given-names>
</name>
</person-group>
<article-title>Nocturnal oxyhemoglobin desaturation in COPD patients with arterial oxygen tensions above 60 mm hg</article-title>
<source>Chest.</source>
<year>1987</year>
<volume>92</volume>
<issue>4</issue>
<fpage>604</fpage>
<lpage>608</lpage>
<pub-id pub-id-type="doi">10.1378/chest.92.4.604</pub-id>
<pub-id pub-id-type="pmid">3652746</pub-id>
</element-citation>
</ref>
<ref id="CR16"><label>16.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Miller</surname>
<given-names>MR</given-names>
</name>
<name><surname>Hankinson</surname>
<given-names>J</given-names>
</name>
<name><surname>Brusasco</surname>
<given-names>V</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Standardisation of spirometry</article-title>
<source>Eur Respir J</source>
<year>2005</year>
<volume>26</volume>
<issue>2</issue>
<fpage>319</fpage>
<lpage>338</lpage>
<pub-id pub-id-type="doi">10.1183/09031936.05.00034805</pub-id>
<pub-id pub-id-type="pmid">16055882</pub-id>
</element-citation>
</ref>
<ref id="CR17"><label>17.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wanger</surname>
<given-names>J</given-names>
</name>
<name><surname>Clausen</surname>
<given-names>JL</given-names>
</name>
<name><surname>Coates</surname>
<given-names>A</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Standardisation of the measurement of lung volumes</article-title>
<source>Eur Respir J</source>
<year>2005</year>
<volume>26</volume>
<issue>3</issue>
<fpage>511</fpage>
<lpage>522</lpage>
<pub-id pub-id-type="doi">10.1183/09031936.05.00035005</pub-id>
<pub-id pub-id-type="pmid">16135736</pub-id>
</element-citation>
</ref>
<ref id="CR18"><label>18.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>MacIntyre</surname>
<given-names>N</given-names>
</name>
<name><surname>Crapo</surname>
<given-names>RO</given-names>
</name>
<name><surname>Viegi</surname>
<given-names>G</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Standardisation of the single-breath determination of carbon monoxide uptake in the lung</article-title>
<source>Eur Respir J</source>
<year>2005</year>
<volume>26</volume>
<issue>4</issue>
<fpage>720</fpage>
<lpage>735</lpage>
<pub-id pub-id-type="doi">10.1183/09031936.05.00034905</pub-id>
<pub-id pub-id-type="pmid">16204605</pub-id>
</element-citation>
</ref>
<ref id="CR19"><label>19.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><collab>ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories</collab>
</person-group>
<article-title>ATS statement: guidelines for the six-minute walk test</article-title>
<source>Am J Respir Crit Care Med</source>
<year>2002</year>
<volume>166</volume>
<issue>1</issue>
<fpage>111</fpage>
<lpage>117</lpage>
<pub-id pub-id-type="doi">10.1164/ajrccm.166.1.at1102</pub-id>
<pub-id pub-id-type="pmid">12091180</pub-id>
</element-citation>
</ref>
<ref id="CR20"><label>20.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lang</surname>
<given-names>RM</given-names>
</name>
<name><surname>Badano</surname>
<given-names>LP</given-names>
</name>
<name><surname>Mor-Avi</surname>
<given-names>V</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging</article-title>
<source>Eur Heart J Cardiovasc Imaging</source>
<year>2015</year>
<volume>16</volume>
<issue>3</issue>
<fpage>233</fpage>
<lpage>270</lpage>
<pub-id pub-id-type="doi">10.1093/ehjci/jev014</pub-id>
<pub-id pub-id-type="pmid">25712077</pub-id>
</element-citation>
</ref>
<ref id="CR21"><label>21.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Voigt</surname>
<given-names>JU</given-names>
</name>
<name><surname>Pedrizzetti</surname>
<given-names>G</given-names>
</name>
<name><surname>Lysyansky</surname>
<given-names>P</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging</article-title>
<source>Eur Heart J Cardiovasc Imaging</source>
<year>2015</year>
<volume>16</volume>
<issue>1</issue>
<fpage>1</fpage>
<lpage>11</lpage>
<pub-id pub-id-type="doi">10.1093/ehjci/jeu184</pub-id>
<pub-id pub-id-type="pmid">25525063</pub-id>
</element-citation>
</ref>
<ref id="CR22"><label>22.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nagueh</surname>
<given-names>SF</given-names>
</name>
<name><surname>Smiseth</surname>
<given-names>OA</given-names>
</name>
<name><surname>Appleton</surname>
<given-names>CP</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging</article-title>
<source>J Am Soc Echocardiogr</source>
<year>2016</year>
<volume>29</volume>
<issue>4</issue>
<fpage>277</fpage>
<lpage>314</lpage>
<pub-id pub-id-type="doi">10.1016/j.echo.2016.01.011</pub-id>
<pub-id pub-id-type="pmid">27037982</pub-id>
</element-citation>
</ref>
<ref id="CR23"><label>23.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lancellotti</surname>
<given-names>P</given-names>
</name>
<name><surname>Pellikka</surname>
<given-names>PA</given-names>
</name>
<name><surname>Budts</surname>
<given-names>W</given-names>
</name>
<etal></etal>
</person-group>
<article-title>The clinical use of stress echocardiography in non-Ischaemic heart disease: recommendations from the European Association of Cardiovascular Imaging and the American Society of Echocardiography</article-title>
<source>Eur Heart J Cardiovasc Imaging</source>
<year>2016</year>
<volume>17</volume>
<issue>11</issue>
<fpage>1191</fpage>
<lpage>1229</lpage>
<pub-id pub-id-type="doi">10.1093/ehjci/jew190</pub-id>
<pub-id pub-id-type="pmid">27880640</pub-id>
</element-citation>
</ref>
<ref id="CR24"><label>24.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marin</surname>
<given-names>JM</given-names>
</name>
<name><surname>Carrizo</surname>
<given-names>SJ</given-names>
</name>
<name><surname>Vicente</surname>
<given-names>E</given-names>
</name>
<name><surname>Agusti</surname>
<given-names>AG</given-names>
</name>
</person-group>
<article-title>Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study</article-title>
<source>Lancet</source>
<year>2005</year>
<volume>365</volume>
<issue>9464</issue>
<fpage>1046</fpage>
<lpage>1053</lpage>
<pub-id pub-id-type="doi">10.1016/S0140-6736(05)71141-7</pub-id>
<pub-id pub-id-type="pmid">15781100</pub-id>
</element-citation>
</ref>
<ref id="CR25"><label>25.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Punjabi</surname>
<given-names>NM</given-names>
</name>
</person-group>
<article-title>The epidemiology of adult obstructive sleep apnea</article-title>
<source>Proc Am Thorac Soc</source>
<year>2008</year>
<volume>5</volume>
<issue>2</issue>
<fpage>136</fpage>
<lpage>143</lpage>
<pub-id pub-id-type="doi">10.1513/pats.200709-155MG</pub-id>
<pub-id pub-id-type="pmid">18250205</pub-id>
</element-citation>
</ref>
<ref id="CR26"><label>26.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shahar</surname>
<given-names>E</given-names>
</name>
<name><surname>Whitney</surname>
<given-names>CW</given-names>
</name>
<name><surname>Redline</surname>
<given-names>S</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the sleep heart health study</article-title>
<source>Am J Respir Crit Care Med</source>
<year>2001</year>
<volume>163</volume>
<issue>1</issue>
<fpage>19</fpage>
<lpage>25</lpage>
<pub-id pub-id-type="doi">10.1164/ajrccm.163.1.2001008</pub-id>
<pub-id pub-id-type="pmid">11208620</pub-id>
</element-citation>
</ref>
<ref id="CR27"><label>27.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yaggi</surname>
<given-names>HK</given-names>
</name>
<name><surname>Concato</surname>
<given-names>J</given-names>
</name>
<name><surname>Kernan</surname>
<given-names>WN</given-names>
</name>
<name><surname>Lichtman</surname>
<given-names>JH</given-names>
</name>
<name><surname>Brass</surname>
<given-names>LM</given-names>
</name>
<name><surname>Mohsenin</surname>
<given-names>V</given-names>
</name>
</person-group>
<article-title>Obstructive sleep apnea as a risk factor for stroke and death</article-title>
<source>N Engl J Med</source>
<year>2005</year>
<volume>353</volume>
<issue>19</issue>
<fpage>2034</fpage>
<lpage>2041</lpage>
<pub-id pub-id-type="doi">10.1056/NEJMoa043104</pub-id>
<pub-id pub-id-type="pmid">16282178</pub-id>
</element-citation>
</ref>
<ref id="CR28"><label>28.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gondi</surname>
<given-names>S</given-names>
</name>
<name><surname>Dokainish</surname>
<given-names>H</given-names>
</name>
</person-group>
<article-title>Right ventricular tissue Doppler and strain imaging: ready for clinical use?</article-title>
<source>Echocardiography</source>
<year>2007</year>
<volume>24</volume>
<issue>5</issue>
<fpage>522</fpage>
<lpage>532</lpage>
<pub-id pub-id-type="doi">10.1111/j.1540-8175.2007.00430.x</pub-id>
<pub-id pub-id-type="pmid">17456072</pub-id>
</element-citation>
</ref>
<ref id="CR29"><label>29.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>D’Andrea</surname>
<given-names>A</given-names>
</name>
<name><surname>Martone</surname>
<given-names>F</given-names>
</name>
<name><surname>Liccardo</surname>
<given-names>B</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Acute and chronic effects of noninvasive ventilation on left and right myocardial function in patients with obstructive sleep apnea syndrome: a speckle tracking echocardiographic study</article-title>
<source>Echocariography</source>
<year>2016</year>
<volume>33</volume>
<issue>8</issue>
<fpage>1144</fpage>
<lpage>1155</lpage>
<pub-id pub-id-type="doi">10.1111/echo.13225</pub-id>
</element-citation>
</ref>
<ref id="CR30"><label>30.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Buonauro</surname>
<given-names>A</given-names>
</name>
<name><surname>Galderisi</surname>
<given-names>M</given-names>
</name>
<name><surname>Santoro</surname>
<given-names>C</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Obstructive sleep apnoea and right ventricular function: a combined assessment by speckle tracking and three-dimensional echocardiography</article-title>
<source>Int J Cardiol</source>
<year>2017</year>
<volume>243</volume>
<fpage>544</fpage>
<lpage>549</lpage>
<pub-id pub-id-type="doi">10.1016/j.ijcard.2017.05.002</pub-id>
<pub-id pub-id-type="pmid">28526545</pub-id>
</element-citation>
</ref>
<ref id="CR31"><label>31.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bodez</surname>
<given-names>D</given-names>
</name>
<name><surname>Lang</surname>
<given-names>S</given-names>
</name>
<name><surname>Meuleman</surname>
<given-names>C</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Left ventricular diastolic dysfunction in obstructive sleep apnoea syndrome by an echocardiographic standardized approach: an observational study</article-title>
<source>Arch Cardiovasc Dis.</source>
<year>2015</year>
<volume>108</volume>
<issue>10</issue>
<fpage>480</fpage>
<lpage>490</lpage>
<pub-id pub-id-type="doi">10.1016/j.acvd.2015.03.006</pub-id>
<pub-id pub-id-type="pmid">26068195</pub-id>
</element-citation>
</ref>
<ref id="CR32"><label>32.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arias</surname>
<given-names>MA</given-names>
</name>
<name><surname>Garcia-Rio</surname>
<given-names>F</given-names>
</name>
<name><surname>Alonso-Fernandez</surname>
<given-names>A</given-names>
</name>
<name><surname>Mediano</surname>
<given-names>O</given-names>
</name>
<name><surname>Martinez</surname>
<given-names>I</given-names>
</name>
<name><surname>Villamor</surname>
<given-names>J</given-names>
</name>
</person-group>
<article-title>Obstructive sleep apnea syndrome affects left ventricular diastolic function: effects of nasal continuous positive airway pressure in men</article-title>
<source>Circulation</source>
<year>2005</year>
<volume>112</volume>
<issue>3</issue>
<fpage>375</fpage>
<lpage>383</lpage>
<pub-id pub-id-type="doi">10.1161/CIRCULATIONAHA.104.501841</pub-id>
<pub-id pub-id-type="pmid">16009798</pub-id>
</element-citation>
</ref>
<ref id="CR33"><label>33.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Baguet</surname>
<given-names>JP</given-names>
</name>
<name><surname>Barone-Rochette</surname>
<given-names>G</given-names>
</name>
<name><surname>Levy</surname>
<given-names>P</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Left ventricular diastolic dysfunction is linked to severity of obstructive sleep apnoea</article-title>
<source>Eur Respir J</source>
<year>2010</year>
<volume>36</volume>
<issue>6</issue>
<fpage>1323</fpage>
<lpage>1329</lpage>
<pub-id pub-id-type="doi">10.1183/09031936.00165709</pub-id>
<pub-id pub-id-type="pmid">20562120</pub-id>
</element-citation>
</ref>
<ref id="CR34"><label>34.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fung</surname>
<given-names>JW</given-names>
</name>
<name><surname>Li</surname>
<given-names>TS</given-names>
</name>
<name><surname>Choy</surname>
<given-names>DK</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Severe obstructive sleep apnea is associated with left ventricular diastolic dysfunction</article-title>
<source>Chest</source>
<year>2002</year>
<volume>121</volume>
<issue>2</issue>
<fpage>422</fpage>
<lpage>429</lpage>
<pub-id pub-id-type="doi">10.1378/chest.121.2.422</pub-id>
<pub-id pub-id-type="pmid">11834652</pub-id>
</element-citation>
</ref>
<ref id="CR35"><label>35.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ha</surname>
<given-names>JW</given-names>
</name>
<name><surname>Lulic</surname>
<given-names>F</given-names>
</name>
<name><surname>Bailey</surname>
<given-names>KR</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Effects of treadmill exercise on mitral inflow and annular velocities in healthy adults</article-title>
<source>Am J Cardiol</source>
<year>2003</year>
<volume>91</volume>
<issue>1</issue>
<fpage>114</fpage>
<lpage>115</lpage>
<pub-id pub-id-type="doi">10.1016/S0002-9149(02)03016-3</pub-id>
<pub-id pub-id-type="pmid">12505590</pub-id>
</element-citation>
</ref>
<ref id="CR36"><label>36.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oh</surname>
<given-names>JK</given-names>
</name>
<name><surname>Kane</surname>
<given-names>GC</given-names>
</name>
</person-group>
<article-title>Diastolic stress echocardiography: the time has come for its integration into clinical practice</article-title>
<source>J Am Soc Echocardiogr</source>
<year>2014</year>
<volume>27</volume>
<issue>10</issue>
<fpage>1060</fpage>
<lpage>1063</lpage>
<pub-id pub-id-type="doi">10.1016/j.echo.2014.08.013</pub-id>
<pub-id pub-id-type="pmid">25249511</pub-id>
</element-citation>
</ref>
<ref id="CR37"><label>37.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kane</surname>
<given-names>GC</given-names>
</name>
<name><surname>Sachdev</surname>
<given-names>A</given-names>
</name>
<name><surname>Villarraga</surname>
<given-names>HR</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Impact of age on pulmonary artery systolic pressures at rest and with exercise</article-title>
<source>Echo Res Prac</source>
<year>2016</year>
<volume>3</volume>
<issue>2</issue>
<fpage>53</fpage>
<lpage>61</lpage>
<pub-id pub-id-type="doi">10.1530/ERP-16-0006</pub-id>
</element-citation>
</ref>
<ref id="CR38"><label>38.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ha</surname>
<given-names>JW</given-names>
</name>
<name><surname>Choi</surname>
<given-names>D</given-names>
</name>
<name><surname>Park</surname>
<given-names>S</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Determinants of exercise-induced pulmonary hypertension in patients with normal left ventricular ejection fraction</article-title>
<source>Heart</source>
<year>2009</year>
<volume>95</volume>
<issue>6</issue>
<fpage>490</fpage>
<lpage>494</lpage>
<pub-id pub-id-type="doi">10.1136/hrt.2007.139295</pub-id>
<pub-id pub-id-type="pmid">18653569</pub-id>
</element-citation>
</ref>
<ref id="CR39"><label>39.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Burgess</surname>
<given-names>MI</given-names>
</name>
<name><surname>Jenkins</surname>
<given-names>C</given-names>
</name>
<name><surname>Sharman</surname>
<given-names>JE</given-names>
</name>
<name><surname>Marwick</surname>
<given-names>TH</given-names>
</name>
</person-group>
<article-title>Diastolic stress echocardiography: hemodynamic validation and clinical significance of estimation of ventricular filling pressure with exercise</article-title>
<source>J Am Coll Cardiol</source>
<year>2006</year>
<volume>47</volume>
<issue>9</issue>
<fpage>1891</fpage>
<lpage>1900</lpage>
<pub-id pub-id-type="doi">10.1016/j.jacc.2006.02.042</pub-id>
<pub-id pub-id-type="pmid">16682317</pub-id>
</element-citation>
</ref>
<ref id="CR40"><label>40.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ha</surname>
<given-names>JW</given-names>
</name>
<name><surname>Oh</surname>
<given-names>JK</given-names>
</name>
<name><surname>Pellikka</surname>
<given-names>PA</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Diastolic stress echocardiography: a novel noninvasive diagnostic test for diastolic dysfunction using supine bicycle exercise Doppler echocardiography</article-title>
<source>J Am Soc Echocardiogr</source>
<year>2005</year>
<volume>18</volume>
<issue>1</issue>
<fpage>63</fpage>
<lpage>68</lpage>
<pub-id pub-id-type="doi">10.1016/j.echo.2004.08.033</pub-id>
<pub-id pub-id-type="pmid">15637491</pub-id>
</element-citation>
</ref>
</ref-list>
</back>
</pmc>
</record>
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