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(5) The studies described in this thesis were performed at the Department of Cardiology of the Leiden University Medical Center, Leiden, The Netherlands Cover: Lay-out: Print: ISBN:

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(1)Cover Page. The handle http://hdl.handle.net/1887/72625 holds various files of this Leiden University dissertation. Author: Hensen, L.C.R. Title: Cardiac mechanics in chronic kidney disease Issue Date: 2019-05-15.

(2) CARDIAC MECHANICS IN CHRONIC KIDNEY DISEASE. Liselotte Liselotte C.R. C.R. Hensen Hensen.

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(4) C ARDIAC MECHANICS IN CHRONIC KIDNEY DISEA SE. LISELOT TE C ATHARINA ROS ALINA HENSEN.

(5) The studies described in this thesis were performed at the Department of Cardiology of the Leiden University Medical Center, Leiden, The Netherlands Cover: Lay-out: Print: ISBN:. Lisanne Zwertbroek Elisa Calamita, persoonlijkproefschrift.nl Ipskamp Printing, proefschriften.net 978-94-028-1407-1. Copyright © 2019 L.C.R. Hensen. All right reserved. No part of this thesis may be reproduced stored or transmitted in any way or by any means without the prior persmission of the author, or when applicable, of the publishers of the ÃVˆi˜ÌˆwV«>«iÀà ˆ˜>˜Vˆ> ÃÕ««œÀÌ LÞ Ì i

(6) ÕÌV  ˆ`˜iÞ œÕ˜`>̈œ˜] *wâiÀ °6°] Ƃ  Ƃ," i`ˆÃV ii˜6Àˆi iÀœi«i˜]-iÀۈiÀ i`iÀ>˜`>À“> °6°]ƂÃÌi>Ã* >À“> °6°] ˆ«ÃœvÌ °6°] ˆœÌÀœ˜ˆŽ i`iÀ>˜` °6°]/ iÀ>Li* >À“> i`iÀ>˜` °6° >˜` œi Àˆ˜}iÀ ˜}i iˆ“ °6° vœÀ Ì i «ÕLˆV>̈œ˜ œv Ì ˆÃ Ì iÈà ˆÃ }À>ÌivՏÞ acknowledged.

(7) CARDIAC MECHANICS IN CHRONIC KIDNEY DISEASE. Proefschrift. ter verkrijging van de graad van Doctor aan de Universiteit Leiden, œ«}iâ>}Û>˜,iV̜À>}˜ˆwVÕëÀœv°“À° °°°°-̜ŽiÀ] volgens besluit van het College voor Promoties te verdedigen op woensdag 15 mei 2019 klokke 16:15 uur. door. Liselotte Catharina Rosalina Hensen geboren te Heemstede in 1989.

(8) Promotor:   .  .  . *Àœv°`À°°7°Վi“> *Àœv°`À°°° >Ý. Co-promotor: . .

(9) À°°°,œÌ“>˜Ã. Leden promotiecommissie:            . *Àœv°`À°°°-V >ˆ *Àœv°`À°° °°,iˆ˜`iÀà *Àœv°`À°Ƃ°Ƃ°6œœÀí1 ]Àœ˜ˆ˜}i˜®

(10) À°°7°°6Àˆi˜`­>}><ˆiŽi˜ ՈÃ]

(11) i˜>>}®. Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged.

(12) . The journey of a thousand miles begins with one single step >œ<ˆ­V>°Èä{‡xäÇÛ° À°®. 6œœÀ“ˆ˜œÕ`iÀÃ.

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(14) TABLE OF CONTENTS Chapter 1. i˜iÀ>ˆ˜ÌÀœ`ÕV̈œ˜>˜`œÕ̏ˆ˜iœvÌ iÌ iÈÃ. 9. Part 1 Left ventricular systolic dysfunction in chronic kidney disease Chapter 2. Prevalence of left ventricular systolic dysfunction in pre-dialysis and dialysis patients with preserved left ventricular ejection fraction. 19. Chapter 3. Prognostic implications of left ventricular global longitudinal strain in pre-dialysis and dialysis patients. 39. Chapter 4. Left ventricular mechanical dispersion and global longitudinal strain and ventricular arrhythmias in pre-dialysis and dialysis patients. 53. Part 2 Valvular heart disease in chronic kidney disease Chapter 5. 6>ÛՏ>À i>ÀÌ`ˆÃi>Ãiˆ˜«Ài‡`ˆ>ÞÈÃ>˜` dialysis patients: prognostic implications. 73. Chapter 6. Prevalence and prognostic implications of mitral and aortic valve calcium in patients with chronic kidney disease. 93. 2CTV#VTKCNƂDTKNNCVKQPKPEJTQPKEMKFPG[FKUGCUG Chapter 7. Echocardiographic associates of atrial wLÀˆ>̈œ˜ˆ˜i˜`‡ÃÌ>}iÀi˜>`ˆÃi>Ãi. 109. Chapter 8. Summary, conclusions and future perspectives. 127. Chapter 9. Samenvatting, conclusies en toekomstperspectieven. 133. Ƃ««i˜`ˆÝ. List of publications. 140. Dankwoord. 141. ÕÀÀˆVՏՓ6ˆÌ>i. 143.

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(16) Chapter 1 GENER AL INTRODUC TION AND OUTLINE OF THE THESIS.

(17) Chapter 1. GENERAL INTRODUCTION AND OUTLINE OF THE THESIS Introduction. Àœ˜ˆVŽˆ`˜iÞ`ˆÃi>Ãi­ 

(18) ®ˆÃ>ܜÀ`܈`i}ÀœÜˆ˜}i«ˆ`i“ˆV>ÃÜVˆ>Ìi`ÜˆÌ  an increased risk of cardiovascular morbidity and mortality.1-4 Heart failure is particularly frequent among patients with CKD.2 Pressure and volume overload >˜`˜œ˜‡ i“œ`ޘ>“ˆVv>V̜ÀÃ>ÃÜVˆ>Ìi`ÜˆÌ  

(19) ˆ˜`ÕViivÌÛi˜ÌÀˆVՏ>À­6® Þ«iÀÌÀœ« Þ]Ài`ÕViV>«ˆ>ÀÞ`i˜ÃˆÌÞ>˜`ˆ˜VÀi>Ãi“ÞœV>À`ˆ>wLÀœÃˆÃÌ >̏i>` ̜6`ˆ>Ã̜ˆV>˜`ÃÞÃ̜ˆV`ÞÃv՘V̈œ˜°5 These processes have been proposed as important determinants of increased mortality in this population.5 The most frequent cause of death in patients with advanced CKD is sudden cardiac death; there is an enhanced arrhythmogenicity due to an increased «ÀiÛ>i˜ViœvV>À`ˆ>VÀˆÃŽv>V̜ÀÃÃÕV >ÃVœÀœ˜>ÀÞ>ÀÌiÀÞ`ˆÃi>Ãi]6 Þ«iÀÌÀœ« Þ >˜`“ÞœV>À`ˆ>wLÀœÃˆÃ]>ÃÜi>Øœ˜‡V>À`ˆ>V­ 

(20) ‡Ã«iVˆwV®ÀˆÃŽv>V̜ÀÃÃÕV  as electrolyte alterations, sympathetic hyperactivity, uremia and anemia. 2,6 Patients with CKD also have an increased risk for developing valvular heart disease due to hemodynamic factors and metabolic pathways that promote Û>ÛՏ>À V>VˆwV>̈œ˜] V>À`ˆ>V `ˆ>Ì>̈œ˜ >˜` ˆ˜viV̈Ûi i˜`œV>À`ˆÌˆÃ°7,8 Finally, >ÌÀˆ>wLÀˆ>̈œ˜ˆÃ«>À̈VՏ>ÀÞvÀiµÕi˜Ìˆ˜«>̈i˜ÌÃÜˆÌ >`Û>˜Vi` 

(21) `Õi̜ electrical and structural remodeling of the atrial myocardium as a consequence of hemodynamic and metabolic disturbances.9-13 Left ventricular systolic dysfunction in patients with chronic kidney disease 6iiV̈œ˜vÀ>V̈œ˜­6 ®]V>VՏ>Ìi`vÀœ“Ìܜ‡`ˆ“i˜Ãˆœ˜>iV œV>À`ˆœ}À>« Þ] ˆÃÌ i“œÃÌvÀiµÕi˜ÌÞÕÃi`«>À>“iÌiÀ̜`iw˜i6ÃÞÃ̜ˆV­`ÞÇ®v՘V̈œ˜14, and is strongly associated with HF and increased mortality in patients with CKD.15,16 œÜiÛiÀ]6  >ÃLii˜à œÜ˜À>Ì iÀˆ˜Ãi˜ÃˆÌˆÛi̜Ì i`iÌiV̈œ˜œv6ÃÞÃ̜ˆV `ÞÃv՘V̈œ˜]«>À̈VՏ>ÀÞˆ˜«>̈i˜ÌÃÜˆÌ  

(22) °˜Ì iÃi«>̈i˜ÌÃ]6 Þ«iÀÌÀœ« Þ >˜` V >˜}ià ˆ˜ Ì i 6 ÃÌÀÕVÌÕÀi “>Þ i>` ̜ ÃÕL̏i 6 ÃÞÃ̜ˆV `ÞÃv՘V̈œ˜ `iëˆÌi«ÀiÃiÀÛi`6 °17 In the last years, several advances in echocardiography ÀiÃՏÌi`ˆ˜˜œÛiˆ˜`ˆViȘœÀ`iÀ̜ˆ“«ÀœÛiV >À>VÌiÀˆâ>̈œ˜œv6v՘V̈œ˜°/ܜ‡ dimensional speckle tracking echocardiography provides more insight in cardiac “iV >˜ˆVÃ>˜`6«iÀvœÀ“>˜Vi°6}œL>œ˜}ˆÌÕ`ˆ˜>ÃÌÀ>ˆ˜­-®]>ÃÃiÃÃi`ÜˆÌ  two-dimensional speckle tracking echocardiography, may provide more detailed ˆ˜vœÀ“>̈œ˜œ˜6ÃÞÃ̜ˆVv՘V̈œ˜°18 9iÌ]`>Ì>œ˜Ì i«ÀiÛ>i˜ViœvÃÕL̏i6 ÃÞÃ̜ˆV`ÞÃv՘V̈œ˜]>VVœÀ`ˆ˜}̜6-ˆ˜«>̈i˜ÌÃÜˆÌ  

(23) >˜`«ÀiÃiÀÛi`. 10.

(24) General Introduction. 6  >Ûi˜œÌLii˜iÝ«œÀi`̜`>Ìi°/ iˆ˜VÀi“i˜Ì>«Àœ}˜œÃ̈VÛ>Õiœv6 -œÛiÀ6  >ÃLii˜`i“œ˜ÃÌÀ>Ìi`ˆ˜«>̈i˜ÌÃÜˆÌ Û>ÀˆœÕÃV>À`ˆœÛ>ÃVՏ>À `ˆÃi>Ãià ­ˆÃV i“ˆV i>ÀÌ `ˆÃi>Ãi] Û>ÛՏ>À i>ÀÌ `ˆÃi>Ãi >˜` i>ÀÌ v>ˆÕÀi®°19 œÜiÛiÀ]ˆÌ̏iˆÃŽ˜œÜ˜>LœÕÌÌ i>ÃÜVˆ>̈œ˜LiÌÜii˜6->˜`ÃÕÀۈÛ>ˆ˜ patients with CKD.19 6 “iV >˜ˆV> `ˆÃ«iÀȜ˜ Ài«ÀiÃi˜Ìà 6 “iV >˜ˆV> `ÞÃÃޘV Àœ˜Þ >˜` ˆÃ “i>ÃÕÀi`ÜˆÌ Ìܜ‡`ˆ“i˜Ãˆœ˜>ëiVŽiÌÀ>VŽˆ˜}iV œV>À`ˆœ}À>« Þ°6->˜` 6“iV >˜ˆV>`ˆÃ«iÀȜ˜>Ài«œÌi˜Ìˆ>ÀˆÃŽ“>ÀŽiÀÃœvÛi˜ÌÀˆVՏ>À>ÀÀ ÞÌ “ˆ>Ș «>̈i˜ÌÃÜˆÌ  

(25) °*>̈i˜ÌÃÜˆÌ >`Û>˜Vi` 

(26) “>ÞLi˜iwÌvÀœ“>˜ˆ“«>˜Ì>Li V>À`ˆœÛiÀÌiÀ`iwLÀˆ>̜À­

(27) ®vœÀ«ÀiÛi˜Ìˆœ˜œvÃÕ``i˜V>À`ˆ>V`i>Ì °œÜiÛiÀ] they also show an increased risk of ICD-related complications.20-22 Therefore, Ì iÀi ˆÃ >˜ ՘“iÌ ˜ii` vœÀ >VVÕÀ>Ìi ÀˆÃŽ ÃÌÀ>̈wV>̈œ˜ ̜œÃ ̜ ˆ`i˜ÌˆvÞ 

(28)  patients at risk of ventricular arrhythmias and sudden cardiac death. Valvular heart disease in patients with chronic kidney disease Patients with CKD have an increased risk for developing valvular heart disease, however they are often denied or not referred to surgery due to the increased operative risk.23,24/ i«Àœ}˜œÃ̈Vˆ“«ˆV>̈œ˜Ãœv՘ÌÀi>Ìi`ÃiÛiÀi6

(29) ˆ˜Ì i }i˜iÀ>«œ«Õ>̈œ˜>ÀiÜiŽ˜œÜ˜]LÕÌ >Ûi˜œÌLii˜ÃÌÕ`ˆi`iÝÌi˜ÃˆÛiÞˆ˜ patients with CKD.25 Underscoring the need of additional studies regarding the prevalence of valvular heart disease in patients with CKD and the frequency of referral for surgical or transcatheter valve intervention. In CKD patients, valvular calcium is an important underlying mechanism œvÛ>Ûi`ÞÃv՘V̈œ˜°6>ÛՏ>ÀV>VˆÕ“ˆÃ>ÃÜVˆ>Ìi`ÜˆÌ >˜ˆ˜VÀi>Ãi`ÀˆÃŽœv all-cause mortality in patients with end-stage renal disease.26,27 However, the prognostic implications of left-sided valve calcium in patients with stage 2 and Î 

(30) ­i,œvÈä‡n™“ɓˆ˜É£°ÇΓÔ>˜`Îä‡x™“ɓˆ˜É£°ÇΓÔÀiëiV̈ÛiÞ® are unknown. #VTKCNƂDTKNNCVKQPKPRCVKGPVUYKVJEJTQPKEMKFPG[FKUGCUG ƂÌÀˆ>wLÀˆ>̈œ˜ˆÃÛiÀÞVœ““œ˜ˆ˜i˜`‡ÃÌ>}iÀi˜>`ˆÃi>Ãi«>̈i˜ÌÃ>˜`Ì i ˆ˜Vˆ`i˜Viœv˜i܏Þ`ˆ>}˜œÃi`>ÌÀˆ>wLÀˆ>̈œ˜ˆ˜œ`iÀ«>̈i˜ÌȘˆÌˆ>̈˜}`ˆ>ÞÈà is 5-fold higher than in the general population.9-11 Electrical and structural Ài“œ`iˆ˜}œvÌ i>ÌÀˆ>“ÞœV>À`ˆÕ“ÃiÀÛiÃ>Ã>ÃÕLÃÌÀ>ÌivœÀ>ÌÀˆ>wLÀˆ>̈œ˜°12 In patients with end-stage renal disease, the metabolic and hemodynamic `ˆÃÌÕÀL>˜ViÃ>ÃÜVˆ>Ìi`ÜˆÌ `ˆ>ÞÈÓ>Þ“œ`Տ>ÌiÌ i>ÌÀˆ>wLÀˆ>̈œ˜ÃÕLÃÌÀ>Ìi. 11.

(31) Chapter 1. Vœ˜ÌÀˆLṎ˜}̜Ì i ˆ} ˆ˜Vˆ`i˜Viœv>ÌÀˆ>wLÀˆ>̈œ˜°13 To date, the structural Ài“œ`iˆ˜}œvÌ iivÌ>ÌÀˆÕ“ >ØœÌLii˜V >À>VÌiÀˆâi`ˆ˜Ì ˆÃ}ÀœÕ«œv«>̈i˜Ìð Outline of the thesis The aim of this thesis was to evaluate cardiac mechanics using two-dimensional ­Ã«iVŽi ÌÀ>VŽˆ˜}® iV œV>À`ˆœ}À>« Þ >˜` VœÀœ˜>ÀÞ Vœ“«ÕÌi` ̜“œ}À>« Þ >˜}ˆœ}À>« Þ ˆ˜ «>̈i˜ÌÃ ÜˆÌ  

(32)  ̜ `iw˜i Ì i «ÀiÛ>i˜Vi >˜` «Àœ}˜œÃ̈V implications of cardiovascular diseases. In Part 1 the value of two-dimensional speckle tracking echocardiography was ˆ˜ÛiÃ̈}>Ìi`vœÀ>ÃÃiÃȘ}6->˜`6“iV >˜ˆV>`ˆÃ«iÀȜ˜ˆ˜«>̈i˜ÌÃÜˆÌ  CKD and its prognostic implications. Chapter 2 >˜>ÞÃiÃ6-]>ÃÃiÃÃi`LÞ two-dimensional speckle tracking echocardiography, in pre-dialysis and dialysis «>̈i˜ÌÃÜˆÌ «ÀiÃiÀÛi`6 °Chapter 3 evaluates the prognostic implications œv6-ˆ˜«Ài‡`ˆ>ÞÈÃ>˜``ˆ>ÞÈë>̈i˜ÌðChapter 4 discusses the value of 6“iV >˜ˆV>`ˆÃ«iÀȜ˜>˜`6->ÃÀˆÃŽ“>ÀŽiÀÃœvÛi˜ÌÀˆVՏ>À>ÀÀ ÞÌ “ˆ>à in pre-dialysis and dialysis patients. Part II focuses on the prevalence and prognostic implications of valvular heart disease and mitral and aortic valve calcium in patients with CKD. Chapter 5 investigates the prevalence and prognostic value of valvular heart disease in pre-dialysis and dialysis patients. Chapter 6 describes the prevalence and prognostic implications of mitral and aortic valve calcium in patients with CKD. Part III vœVÕÃiÃœ˜>ÌÀˆ>wLÀˆ>̈œ˜ˆ˜«>̈i˜ÌÃÜˆÌ i˜`‡ÃÌ>}iÀi˜>`ˆÃi>Ãi° Chapter 7 provides more insight on the echocardiographic associates of atrial wLÀˆ>̈œ˜ˆ˜«>̈i˜ÌÃÜˆÌ i˜`‡ÃÌ>}iÀi˜>`ˆÃi>Ãi°. 12.

(33) General Introduction. REFERENCES £° œƂ-] iÀ̜Ü]>˜

(34) ]V ՏœV  CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular iÛi˜ÌÃ]>˜` œÃ«ˆÌ>ˆâ>̈œ˜°N Engl J Med 2004;351:1296-1305. 2. United States Renal Data System. 2016 USRDS annual data repor t: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2016. ΰ 7i˜ *] i˜}/9]/Ã>ˆ] >˜}9 ] Chan HT, Tsai SP, Chiang PH, Hsu CC, -՘}*]ÃÕ9]7i˜-°Ƃ‡V>ÕÃi mortality attributable to chronic kidney disease: a prospective cohort study based on 462 293 adults in Taiwan. Lancet 2008;371:2173-2182. {° >`L>˜ -] Àˆ}>˜Ìˆ ] iÀÀ *]

(35) ՘ÃÌ>˜

(36) 7]7iLœÀ˜/Ƃ]<ˆ““iÌ*<] Atkins RC. Prevalence of kidney damage in Australian adults: The AusDiab kidney study. J Am Soc Nephrol 2003;14:S131138. x° iÀâœ} Ƃ]ƂȘ}iÀ,7] iÀ}iÀƂ]. >ÀÞÌ>˜

(37) ]

(38) ˆiâ]>ÀÌ,] VŽ>À`Ì KU, Kasiske BL, McCullough PA, *>ÃÓ>˜,-]

(39) iœ>V --]*՘*],ˆÌâ ° Cardiovascular disease in chronic kidney disease. A clinical update from Kidney

(40) ˆÃi>Ãi\“«ÀœÛˆ˜}œL>"ÕÌVœ“ià ­

(41) "®°Kidney Int 2011;80:572-586. È° œÀˆ>˜ˆ]->ÛiˆiÛ>]

(42) >˜Ƃ]

(43) i >Àœ  ]iÀÀœ ]ÃÀ>i 7]>˜i

(44) Ƃ]> >˜˜>]œÀ̜˜]ˆÌ>˜ÃƂ]6œÃ Ƃ] /ÕÀ>Ž ˆ> *] ˆ« 9° Àœ˜ˆV kidney disease in patients with cardiac. rhythm disturbances or implantable iiVÌÀˆV>`iۈViÃ\Vˆ˜ˆV>È}˜ˆwV>˜Vi and implications for decision making-a position paper of the European Heart Rhythm Association endorsed by the Heart Rhythm Society and the Asia *>VˆwVi>ÀÌ, ÞÌ “-œVˆiÌÞ°Europace 2015;17:1169-1196. Ç° œ˜`œ˜]*>˜˜ˆiÀ ]>ÀV >ˆÃ-] ÕiÀˆ˜Ƃ*° >VˆwV>̈œ˜œvÌ i>œÀ̈V Û>Ûiˆ˜Ì i`ˆ>Þâi`«>̈i˜Ì°J Am Soc Nephrol 2000;11:778-783. n° ˆ“

(45) ] - ˆ“ 9] œ˜} ,] œ ]. >˜}]>7] ՘} ° vviVÌœv End-Stage Renal Disease on Rate of Progression of Aortic Stenosis. Am J Cardiol 2016;117:1972-1977. 9. Zimmerman D, Sood MM, Rigatto C, Holden RM, Hiremath S, Clase CM. Systematic review and meta-analysis of incidence, prevalence and outcomes of >ÌÀˆ>wLÀˆ>̈œ˜ˆ˜«>̈i˜ÌÃœ˜`ˆ>ÞÈð Nephrol Dial Transplant 2012;27:38163822. £ä°œ`ÃÌiˆ˜ Ƃ]ƂÀVi ]>̎ÞƂ] /ÕÀ>Ž ˆ>]-i̜}ÕV ˆ-]7ˆ˜Ži“>ÞiÀ 7 °/Ài˜`È˜Ì iˆ˜Vˆ`i˜Viœv>ÌÀˆ> wLÀˆ>̈œ˜ˆ˜œ`iÀ«>̈i˜ÌȘˆÌˆ>̈˜} dialysis in the United States. Circulation 2012;126:2293-2301. 11.*ˆVVˆ˜ˆ *] >““ˆ ] -ˆ˜˜iÀ ] i˜Ãi˜* ]iÀ˜>˜`iâƂ]iVŽLiÀÌ -,] i˜>“ˆ˜ ] ÕÀ̈ð˜Vˆ`i˜Vi >˜`«ÀiÛ>i˜Viœv>ÌÀˆ>wLÀˆ>̈œ˜>˜` associated mortality among Medicare Li˜iwVˆ>ÀˆiÃ]£™™Î‡ÓääÇ°Circ Cardiovasc Qual Outcomes 2012;5:85-93. £Ó°ƂiÃÈi ] ƂÕÓ> ] -V œÌÌi˜ 1° Electrical, contractile and structural Ài“œ`iˆ˜}`ÕÀˆ˜}>ÌÀˆ>wLÀˆ>̈œ˜°. 13.

(46) Chapter 1 Cardiovasc Res 2002;54:230-246. £Î°œÀ>˜Ì✫œÕœÃ*]œŽŽœÀˆÃ-]ˆÕ/] *ÀœÌœ«Ã>ÌˆÃ]ˆ]œÕ`iÛi˜œÃƂ° ƂÌÀˆ> wLÀˆ>̈œ˜ ˆ˜ i˜`‡ÃÌ>}i Ài˜> disease. Pacing Clin Electrophysiol 2007;30:1391-1397. £{°>˜},] >`>˜œ*]œÀ‡Ƃۈ6]Ƃw>œ ]ƂÀ“ÃÌÀœ˜}Ƃ] À˜>˜`i]>V Î>“«v Ƃ]œÃÌiÀ ]œ`ÃÌiˆ˜-Ƃ]Õâ˜iÌÜÛ> T, Lancellotti P, Muraru D, Picard MH, ,ˆiÌâÃV i ,],Õ`Έ]-«i˜ViÀ/] /Ã>˜}7]6œˆ}Ì1°,iVœ““i˜`>̈œ˜Ã for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2015;16:233-270. £x°*>ޘi]- >À“>-]

(47) iiœ˜

(48) ]Õ] Alemu F, Balogun RA, Malakauskas SM, Kalantar-Zadeh K, Kovesdy CP. Association of echocardiographic abnormalities with mortality in men with non-dialysis-dependent chronic kidney disease. Nephrol Dial Transplant 2012;27:694-700. £È°*>ÀvÀiÞ*-]œiÞ, ]>À˜iÌÌ

(49) ]i˜Ì ]ÕÀÀ>Þ

(50) ] >ÀÀi* °"ÕÌVœ“i and risk factors for left ventricular disorders in chronic uraemia. Nephrol Dial Transplant 1996;11:1277-1285. 17. Unger ED, Dubin RF, Deo R, Daruwalla 6]Àˆi`“>˜]i`ˆ˜> ] iÕÃȘŽ ]Àii` ]- > -°ƂÃÜVˆ>̈œ˜œv chronic kidney disease with abnormal cardiac mechanic s and adverse outcomes in patients with heart failure and preserved ejection fraction. Eur J Heart Fail 2016;18:103-112. £n°/œ«Ã]

(51) i}>`œ6]>ÀÃ>˜ Ƃ] >Ý. 14. °ޜV>À`ˆ>ÃÌÀ>ˆ˜̜`iÌiVÌÃÕL̏i left ventricular systolic dysfunction. Eur J Heart Fail 2017;19:307-313. £™°>>“ ] "Ì> > *] >À ܈VŽ /° *Àœ}˜œÃ̈Vˆ“«ˆV>̈œ˜Ãœv}œL>6 dysfunction: a systematic review and meta-analysis of global longitudinal strain and ejection fraction. Heart 2014;100:1673-1680. Óä°ÀiÞLi ] ââi``ˆ˜i ,] i`ˆ ] >ÀÀˆ˜}̜˜7] >â>â,]>˜â]>ˆ˜ -] }ÜÕ"]œ˜`œ˜ ]->L>-°,i˜> ˆ˜ÃÕvwVˆi˜VÞ«Ài`ˆVÌÃÌ ï“i̜wÀÃÌ >««Àœ«Àˆ>Ìi `iwLÀˆ>̜À à œVŽ° Am Heart J 2006;151:852-856. 21. Makki N, Swaminathan PD, Hanmer ] "Ã >˜ÃŽÞ °

(52) œ ˆ“«>˜Ì>Li cardioverter defibrillators improve survival in patients with chronic kidney disease at high risk of sudden cardiac death? A meta-analysis of observational studies. Europace 2014;16:55-62. ÓÓ° ՈÌi˜ -]

(53) i ˆi ] 6>˜

(54) iÀ iˆ`i˜Ƃ ],œÌ“>˜Ã] œœÌÓ>] >ÀVÀœi˜iÛi`]7œÌiÀLiiŽ,] ,>Liˆ˜Ž/]Վi“>7]-V >ˆ]6>˜ Erven L. Chronic kidney disease and ˆ“«>˜Ì>LiV>À`ˆœÛiÀÌiÀ`iwLÀˆ>̜À related complications: 16 years of iÝ«iÀˆi˜Vi°J Cardiovasc Electrophysiol 2014;25:998-1004. Óΰ՘} ] >Àœ˜] ÕÌV >ÀÌ ]

(55) i> >Þi ] œ Ži‡ >Àܜv ] iÛ>˜} "7] /œÀ˜œÃ*]6>˜œÛiÀÃV i`i]6iÀ“iiÀ ] œiÀÓ> ],>Û>Õ`*]6> >˜ˆ>˜Ƃ° A prospective survey of patients with valvular heart disease in Europe: The ÕÀœi>ÀÌ-ÕÀÛiÞœ˜6>ÛՏ>Ài>ÀÌ Disease. Eur Heart J 2003;24:1231-1243. Ó{°iÀâœ} Ƃ]><] œˆ˜ÃƂ°œ˜}‡ÌiÀ“ survival of dialysis patients in the United.

(56) General Introduction States with prosthetic heart valves: à œÕ`Ƃ. ÉƂƂ«À>V̈Vi}Ո`iˆ˜iÃœ˜ Û>ÛiÃiiV̈œ˜Li“œ`ˆwi`¶Circulation 2002;105:1336-1341. Óx° ˆÃ ˆ“ÕÀ>,Ƃ]"Ì̜ ] œ˜œÜ,"]. >À>Liœ Ƃ] À܈˜*]ÎÀ`]ÕÞ̜˜,Ƃ] "½>À>*/],Ոâ ]-ŽÕL>à ]-œÀ>>*] -՘`Ì/]ÎÀ`]/ œ“>Ã

(57) °Óä£{ƂƂÉ ACC guideline for the management of patients with valvular heart disease: a report of the American College of. >À`ˆœœ}ÞÉƂ“iÀˆV>˜i>ÀÌƂÃÜVˆ>̈œ˜ />ÎœÀViœ˜*À>V̈ViՈ`iˆ˜iðJ Am Coll Cardiol 2014;63:e57-185. ÓÈ°,>}}ˆ*] i>ÈƂ]>“Lœ> ]iÀÀ>“œÃV> ],>Ì̈ ] œVŽƂ]՘̘iÀ*°Ƃ‡ cause mortality in hemodialysis patients ÜˆÌ  i>ÀÌÛ>ÛiV>VˆwV>̈œ˜°Clin J Am Soc Nephrol 2011;6:1990-1995. 27. Takahashi H, Ishii H, Aoyama T, Kamoi D, Kasuga H, Ito Y, Yasuda K, Tanaka M, Yoshikawa D, Maruyama S, Matsuo -]ÕÀœ >À>/]9Õâ>Ü>9°ƂÃÜVˆ>̈œ˜ œvV>À`ˆ>VÛ>ÛՏ>ÀV>VˆwV>̈œ˜Ã>˜` C-reactive protein with cardiovascular mortality in incident hemodialysis «>̈i˜ÌÃ\>>«>˜iÃiVœ œÀÌÃÌÕ`Þ°Am J Kidney Dis 2013;61:254-261.. 15.

(58)

(59) Part 1 LEF T VENTRICUL AR SYSTOLIC DYSFUNC TION IN CHRONIC KIDNEY DISE A SE.

(60)

(61) Chapter 2 PREVALENCE OF LEF T VENTRICUL AR SYSTOLIC DYSFUNC TION IN PRE-DIALYSIS AND DIALYSIS PATIENTS WITH PRESERVED LEF T VENTRICUL AR EJEC TION FR AC TION. Liselotte C.R. Hensen >Ì ii˜œœÃÃi˜Ã 6ˆV̜Àˆ>

(62) i}>`œ Rachid Abou œÀˆÃ°,œÌ“>˜Ã °7œÕÌiÀՎi“> iÀœi˜° >Ý. ÕÀi>ÀÌ>ˆ°Óä£nÆÓä­Î®\xÈä‡xÈn.

(63) Chapter 2. ABSTRACT Aims *>̈i˜ÌÃ ÜˆÌ  V Àœ˜ˆV Žˆ`˜iÞ `ˆÃi>Ãi ­ 

(64) ® >Ûi >˜ iÝViÃà œv V>À`ˆœÛ>ÃVՏ>À “œÀLˆ`ˆÌÞ >˜` “œÀÌ>ˆÌÞ ÜˆÌ  i>ÀÌ v>ˆÕÀi ­® Liˆ˜} «>À̈VՏ>ÀÞ vÀiµÕi˜Ì° ,i`ÕVi`ivÌÛi˜ÌÀˆVՏ>À­6®iiV̈œ˜vÀ>V̈œ˜­ ®`iw˜iÃ6ÃÞÃ̜ˆV`ÞÃv՘V̈œ˜ and is associated with poor prognosis. However, CKD patients may have HF Ãޓ«Ìœ“Ã ÜˆÌ  «ÀiÃiÀÛi` 6 ° ˜ Ì ˆÃ ÃÕL}ÀœÕ« œv «>̈i˜ÌÃ] Ӈ`ˆ“i˜Ãˆœ˜> ëiVŽi ÌÀ>VŽˆ˜} iV œV>À`ˆœ}À>« Þ V>˜ `iÌiVÌ 6 ÃÞÃ̜ˆV `ÞÃv՘V̈œ˜ LÞ >˜>ÞȘ}6“ÞœV>À`ˆ>`ivœÀ“>̈œ˜°/ i«ÀiÃi˜ÌÃÌÕ`ÞiÛ>Õ>Ìi`Ì i«ÀiÛ>i˜Vi œvˆ“«>ˆÀi`6}œL>œ˜}ˆÌÕ`ˆ˜>ÃÌÀ>ˆ˜­-®ˆ˜ 

(65) «>̈i˜ÌÃÜˆÌ «ÀiÃiÀÛi` 6 >˜`ˆÌëÀœ}˜œÃ̈VVœ˜ÃiµÕi˜Við Methods and results /ܜ‡ ՘`Ài` «Ài‡`ˆ>ÞÈà >˜` `ˆ>ÞÈà «>̈i˜Ìà ­Èx¯ “i˜] “i>˜ >}i Èä´£{ Þi>ÀîÜˆÌ  

(66) ÃÌ>}iÎL‡x>˜`«ÀiÃiÀÛi`6 ­6 Ĉx䯮ÜiÀiiÛ>Õ>Ìi`° 6ÃÞÃ̜ˆV`ÞÃv՘V̈œ˜`iëˆÌi«ÀiÃiÀÛi`6 Ü>Ã`iw˜i`LÞ6-ć£x°Ó¯ ­VÕ̇œvvÛ>Õi`iÀˆÛi`vÀœ“Ì iÓÃÌ>˜`>À``iۈ>̈œ˜ÃLiœÜÌ i“i>˜Û>Õiœv ˆ˜`ˆÛˆ`Õ>ÃÜˆÌ œÕÌÃÌÀÕVÌÕÀ> i>ÀÌ`ˆÃi>Ãi®°“«>ˆÀi`6-­ć£x°Ó¯®`iëˆÌi «ÀiÃiÀÛi`6 Ü>ÃœLÃiÀÛi`ˆ˜ÎÓ¯œv«>̈i˜Ìð

(67) ÕÀˆ˜}>“i`ˆ>˜vœœÜ‡Õ«œv ÎΓœ˜Ì í+,Æ£Ç]ÈÓ“œ˜Ì î]{ǯœv«>̈i˜ÌÃ՘`iÀÜi˜ÌÀi˜>ÌÀ>˜Ã«>˜Ì>̈œ˜] ™¯ÜiÀi>`“ˆÌÌi`ÜˆÌ  i>ÀÌv>ˆÕÀi>˜`Ón¯`ˆi`°*>̈i˜ÌÃÜˆÌ 6-ć£x°Ó¯ à œÜi`È}˜ˆwV>˜ÌÞܜÀÃiVՓՏ>̈ÛiiÛi˜Ì‡vÀiiÃÕÀۈÛ>À>ÌiÃœvÌ iVœ“Lˆ˜i` endpoint of HF hospitalisation and all-cause mortality compared to patients with 6-€£x°Ó¯­œ}‡À>˜Ž*rä°ä£n®° Conclusion / i«ÀiÛ>i˜Viœvˆ“«>ˆÀi`6-`iëˆÌi«ÀiÃiÀÛi`6 ˆ˜«Ài‡`ˆ>ÞÈÃ>˜` `ˆ>ÞÈë>̈i˜ÌÈÃÀi>̈ÛiÞ ˆ} °*>̈i˜ÌÃÜˆÌ «ÀiÃiÀÛi`6 LṎ“«>ˆÀi`6 - >Ûi>˜ˆ˜VÀi>Ãi`ÀˆÃŽœv œÃ«ˆÌ>ˆÃ>̈œ˜>˜`>‡V>ÕÃi“œÀÌ>ˆÌÞ°. 20.

(68) Impaired LV GLS in CKD and preserved LVEF. INTRODUCTION *>̈i˜ÌÃ ÜˆÌ  V Àœ˜ˆV Žˆ`˜iÞ `ˆÃi>Ãi ­ 

(69) ® iÝ ˆLˆÌ >˜ ˆ˜VÀi>Ãi` ÀˆÃŽ œv V>À`ˆœÛ>ÃVՏ>À“œÀLˆ`ˆÌÞ>˜`“œÀÌ>ˆÌÞ]ÜˆÌ  i>ÀÌv>ˆÕÀi­® œÃ«ˆÌ>ˆâ>̈œ˜ being one of the most frequent cardiovascular events.1 Chronic pressure and ۜÕ“iœÛiÀœ>`>ÃÜi>Øœ˜‡ i“œ`ޘ>“ˆVv>V̜ÀÃ]ÃÕV >Ü݈`>̈ÛiÃÌÀiÃà and inappropriate renin-angiotensin-aldosterone system activation, lead to Ì i`iÛiœ«“i˜ÌœvivÌÛi˜ÌÀˆVՏ>À­6®ÃÞÃ̜ˆV>˜``ˆ>Ã̜ˆV`ÞÃv՘V̈œ˜°26 iiV̈œ˜vÀ>V̈œ˜­6 ®]V>VՏ>Ìi`vÀœ“Ìܜ‡`ˆ“i˜Ãˆœ˜>iV œV>À`ˆœ}À>« Þ] ˆÃÌ i“œÃÌvÀiµÕi˜ÌÞÕÃi`«>À>“iÌiÀ̜`iw˜i6ÃÞÃ̜ˆV­`Þîv՘V̈œ˜]3 and ˆÃÃÌÀœ˜}Þ>ÃÜVˆ>Ìi`ÜˆÌ >˜`ˆ˜VÀi>Ãi`“œÀÌ>ˆÌÞˆ˜Ì ˆÃëiVˆwV}ÀœÕ«œv patients.4,5œÜiÛiÀ]6  >ÃLii˜à œÜ˜À>Ì iÀˆ˜Ãi˜ÃˆÌˆÛi̜Ì i`iÌiV̈œ˜ œv6ÃÞÃ̜ˆV`ÞÃv՘V̈œ˜]«>À̈VՏ>ÀÞˆ˜«>̈i˜ÌÃÜˆÌ  

(70) °˜Ì iÃi«>̈i˜ÌÃ] 6 Þ«iÀÌÀœ« Þ>˜`V >˜}iÈ˜Ì i6ÃÌÀÕVÌÕÀi“>ޏi>`̜ÃÕL̏i6ÃÞÃ̜ˆV `ÞÃv՘V̈œ˜ `iëˆÌi «ÀiÃiÀÛi` 6 °6 6 }œL> œ˜}ˆÌÕ`ˆ˜> ÃÌÀ>ˆ˜ ­-®] assessed with two-dimensional speckle tracking echocardiography, may provide “œÀi`iÌ>ˆi`ˆ˜vœÀ“>̈œ˜œ˜6ÃÞÃ̜ˆVv՘V̈œ˜°7/ i«ÀiÛ>i˜ViœvÃÕL̏i6 ÃÞÃ̜ˆV`ÞÃv՘V̈œ˜]>VVœÀ`ˆ˜}̜6-ˆ˜«>̈i˜ÌÃÜˆÌ  

(71) >˜`«ÀiÃiÀÛi` 6 ˆÃ՘Ž˜œÜ˜°˜>``ˆÌˆœ˜]`>Ì>œ˜Ì i«Àœ}˜œÃ̈VÛ>Õiœv6-ˆ˜Ì ˆÃ «œ«Õ>̈œ˜ÜˆÌ «ÀiÃiÀÛi`6 >Ài>VVՓՏ>̈˜}°8-10 Accordingly, the present ÃÌÕ`Þˆ˜ÛiÃ̈}>Ìi`Ì i«ÀiÛ>i˜Viœvˆ“«>ˆÀi`6-ˆ˜«Ài‡`ˆ>ÞÈÃ>˜``ˆ>ÞÈà «>̈i˜ÌÃÜˆÌ «ÀiÃiÀÛi`6 °ÕÀÌ iÀ“œÀiÌ iÀi>̈œ˜Ã ˆ«LiÌÜii˜6- >˜`Ì iVœ“Lˆ˜i`i˜`«œˆ˜Ìœv œÃ«ˆÌ>ˆâ>̈œ˜>˜`>‡V>ÕÃi“œÀÌ>ˆÌÞ>˜` all-cause mortality alone, was investigated.. METHODS Patient population From an ongoing registry of pre-dialysis and dialysis patients at the Leiden University Medical Centre, The Netherlands,11 «>̈i˜ÌÃ ÜˆÌ  «ÀiÃiÀÛi` 6  ­Ĉx䯮 >˜` iÜ 9œÀŽ i>ÀÌ ƂÃÜVˆ>̈œ˜ v՘V̈œ˜> V>Ãà ‡6] >ÃÃiÃÃi` LÞ transthoracic echocardiography performed during hemodynamic stable conditions, were selected. All patients were diagnosed with chronic kidney `ˆÃi>Ãi­ 

(72) ®ÃÌ>}iÎL‡x>VVœÀ`ˆ˜}̜Ì iÓä£Ó ˆ˜ˆV>*À>V̈ViՈ`iˆ˜ivœÀ Ì i Û>Õ>̈œ˜>˜`>˜>}i“i˜Ìœv 

(73) LÞˆ`˜iÞ

(74) ˆÃi>Ãi\“«ÀœÛˆ˜}œL>. 21.

(75) Chapter 2. "ÕÌVœ“ií

(76) "®°12*>̈i˜ÌÃޜ՘}iÀÌ >˜£nÞi>ÀÃœ`]«>̈i˜ÌÃÜˆÌ 6  x䯜Àˆ˜Ü œ“Ì iiV œV>À`ˆœ}À>« ÞÜ>ëiÀvœÀ“i``ÕÀˆ˜} œÃ«ˆÌ>ˆâ>̈œ˜ vœÀ]>ÃÜi>ë>̈i˜ÌÃÜˆÌ ˆ“ˆÌi`iV œV>À`ˆœ}À>« ˆViÝ>“ˆ˜>̈œ˜œÀÜˆÌ  inadequate image quality for off-ˆ˜i>˜>ÞÈÃ]ÜiÀiiÝVÕ`i`°/ iiiVÌÀœ˜ˆV> “i`ˆV> ÀiVœÀ`à ­ˆ8Æ ˆ«-œvÌ] Ƃ“ÃÌiÀ`>“] / i iÌ iÀ>˜`î >˜` Ì i `i«>À̓i˜Ì> V>À`ˆœœ}Þ ˆ˜vœÀ“>̈œ˜ ÃÞÃÌi“ ­ *

(77) ‡ÛˆÃˆœ˜Æ iˆ`i˜ 1˜ˆÛiÀÈÌÞ i`ˆV> i˜ÌÀi]iˆ`i˜]/ i iÌ iÀ>˜`îÜiÀiÀiۈiÜi`̜VœiVÌÌ iVˆ˜ˆV> `>Ì>°6-Ü>Ói>ÃÕÀi`ÜˆÌ ëiVŽiÌÀ>VŽˆ˜}iV œV>À`ˆœ}À>« Þ°6ÃÞÃ̜ˆV `ÞÃv՘V̈œ˜`iëˆÌi«ÀiÃiÀÛi`6 Ü>Ã`iw˜i`LÞ>Û>Õiœv6-œÜiÀÌ >˜ ÓÃÌ>˜`>À``iۈ>̈œ˜ÃLiœÜÌ i“i>˜Û>Õiœv6-`iÀˆÛi`vÀœ“ˆ˜`ˆÛˆ`Õ>Ã without structural heart disease.13 Patients were followed-up for the occurrence œv œÃ«ˆÌ>ˆâ>̈œ˜>˜`>‡V>ÕÃi“œÀÌ>ˆÌÞ>ÌÌ iiˆ`i˜1˜ˆÛiÀÈÌÞi`ˆV> Centre. The institutional review board approved this retrospective analysis of clinically acquired data and waved the need for patient written informed consent. Clinical characteristics Demographics, cardiovascular risk factors, medication use and laboratory results ÜiÀi ˆ˜VÕ`i` >à L>Ãiˆ˜i Vˆ˜ˆV> Û>Àˆ>Lið Ã̈“>Ìi` }œ“iÀՏ>À wÌÀ>̈œ˜ À>Ìi­i,®Ü>ÃV>VՏ>Ìi`LÞÌ i 

(78)  «ˆ`i“ˆœœ}Þ œ>LœÀ>̈œ˜­ 

(79) ‡ *® equation as recommended.12 Using the concentration of creatinine in a 24-hour urine specimen and the pre-dialysis plasma creatinine concentration, residual renal function was calculated.141ÌÀ>wÌÀ>̈œ˜À>ÌiÜ>ÃV>VՏ>Ìi`>ÃvœœÜÃ\“i>˜ ՏÌÀ>wÌÀ>̈œ˜ۜÕ“i­“®œvxÃiÃȜ˜ÃÉÃiÃȜ˜`ÕÀ>̈œ˜­ œÕÀ®ÉÌ>À}iÌÜiˆ} Ì­Ž}®° Delta systolic blood pressure was calculated by subtracting pre-dialysis systolic Lœœ`«ÀiÃÃÕÀivÀœ“«œÃ̇`ˆ>ÞÈÃÃÞÃ̜ˆVLœœ`«ÀiÃÃÕÀi° Ã̈“>Ìi`,Ü>à only measured in pre-dialysis patients, while residual renal function, dialysis type >˜``ˆ>ÞÈÃۈ˜Ì>}iÜiÀi“i>ÃÕÀi`ˆ˜`ˆ>ÞÈë>̈i˜ÌÃ>˜`ՏÌÀ>wÌÀ>̈œ˜À>Ìi and delta systolic blood pressure in hemodialysis patients. Transthoracic echocardiography Two-dimensional transthoracic echocardiography was performed with the patients in the left lateral decubitus position using commercially available systems ­6ˆÛˆ`ÇœÀ ™]i˜iÀ> iVÌÀˆV6ˆ˜}“i`]ˆÜ>Վii]7]1-Ƃ®iµÕˆ««i`ÜˆÌ  ΰxâœÀx-ÌÀ>˜Ã`ÕViÀð/ iiV œV>À`ˆœ}À>« ˆV`>Ì>ÜiÀi`ˆ}ˆÌ>ÞÃ̜Ài` ˆ˜Vˆ˜iœœ«vœÀ“>ÌvœÀœvv‡ˆ˜i>˜>ÞÈí V œ*>V££Ó°ä°£] i`ˆV>-ÞÃÌi“Ã] œÀÌi˜] œÀÜ>Þ®°Àœ“Ì i«>À>ÃÌiÀ˜>œ˜}‡>݈ÃۈiÜ]ˆ˜i>À`ˆ“i˜Ãˆœ˜ÃœvÌ i. 22.

(80) Impaired LV GLS in CKD and preserved LVEF. ivÌÛi˜ÌÀˆViÜiÀi“i>ÃÕÀi`œ˜‡“œ`iÀiVœÀ`ˆ˜}Ã>˜`6“>ÃÃÜ>Ã`iÀˆÛi` vÀœ“Ì i

(81) iÛiÀiÕÝvœÀ“Տ>>˜`ˆ˜`iÝi`̜Lœ`ÞÃÕÀv>Vi>Ài>°3 Using the biplane -ˆ“«Ãœ˜½Ã“iÌ œ`]6i˜`‡`ˆ>Ã̜ˆV>˜`i˜`‡ÃÞÃ̜ˆVۜÕ“iÃ>˜`6 ÜiÀi measured from the apical 4- and 2-chamber views.3 From the apical 4-chamber ۈiÜ]ivÌ>ÌÀˆ>­Ƃ®ۜÕ“iÜ>Ói>ÃÕÀi`]ÕȘ}Ì i`ˆÃŽÃՓ“>̈œ˜ÌiV ˜ˆµÕi >˜`ˆ˜`iÝi`vœÀLœ`ÞÃÕÀv>Vi>Ài>°/ÀˆVÕëˆ`>˜˜Õ>À«>˜iÃÞÃ̜ˆViÝVÕÀȜ˜ ­/Ƃ*- ®]>Ã>“i>ÃÕÀiœvÀˆ} ÌÛi˜ÌÀˆVՏ>Àv՘V̈œ˜]Ü>Ã>ÃÃiÃÃi`ˆ˜Ì ivœVÕÃi` apical 4-chamber view of the right ventricle applying anatomical M-mode.3 By measuring the width of the vena contracta, mitral regurgitation severity was }À>`i`Ãi“ˆ‡µÕ>˜ÌˆÌ>̈ÛiÞ]vÀœ“VœœÕÀ‡yœÜ

(82) œ««iÀ`>Ì>°15 Peak early diastolic ­ ® >˜` >Ìi `ˆ>Ã̜ˆV ­Ƃ® Ü>Ûi ÛiœVˆÌˆià ÜiÀi “i>ÃÕÀi` ÕȘ} «ÕÃi` Ü>Ûi

(83) œ««iÀÀiVœÀ`ˆ˜}ÃœvÌ i“ˆÌÀ>ˆ˜yœÜ°>ÌiÀ> ½Ü>ÛiÛiœVˆÌÞœvÌ i“ˆÌÀ> >˜˜ÕÕÃÜ>Ói>ÃÕÀi`ÜˆÌ VœœÀ‡Vœ`i`̈ÃÃÕi

(84) œ««iÀˆ“>}ˆ˜}­/

(85) ®ˆ˜Ì i>«ˆV> {‡V >“LiÀۈiÜ̜>ÃÃiÃÃ6Ài>Ý>̈œ˜°/ i É ½À>̈œÜ>Ã`iÀˆÛi`>Ã>“i>ÃÕÀi œv6wˆ˜}«ÀiÃÃÕÀið16/œµÕ>˜ÌˆvÞ6-]Ìܜ‡`ˆ“i˜Ãˆœ˜>ëiVŽi‡ÌÀ>VŽˆ˜} echocardiography was used on standard routine grayscale images of apical 4-, ӇV >“LiÀ>˜`œ˜}‡>݈ÃۈiÜð176-Ü>ëÀœÛˆ`i`LÞÌ iÜvÌÜ>Ài>ÃÌ i average peak systolic longitudinal strain value of the 3 apical views. Normally, 6-ˆÃ«ÀiÃi˜Ìi`>Øi}>̈ÛiÛ>ÕiÃȘViˆÌˆ˜`ˆV>ÌiÃÌ ià œÀÌi˜ˆ˜}œvÌ i “ÞœV>À`ˆÕ“Ài>̈Ûi̜Ì iœÀˆ}ˆ˜>i˜}Ì Æ œÜiÛiÀÌ i“>}˜ˆÌÕ`i­>L܏ÕÌi Û>Õi®œv6-ˆÃ«ÀiÃi˜Ìi`ˆ˜Ì ˆÃ>˜>ÞÈð17 Patients were divided into two }ÀœÕ«Ã>VVœÀ`ˆ˜}̜6-€£x°Ó¯­“œÀi«ÀiÃiÀÛi`®>˜`6-ć£x°Ó¯­“œÀi ˆ“«>ˆÀi`®]>VÕ̇œvvÛ>ÕiœLÌ>ˆ˜i`vÀœ“ÓÃÌ>˜`>À``iۈ>̈œ˜ÃLiœÜÌ i“i>˜ Û>Õiœv6-`iÀˆÛi`vÀœ“ i>Ì ÞVœ˜ÌÀœÃ°13 Follow-up The national death registry and case records were reviewed for the occurrence œv>‡V>ÕÃi“œÀÌ>ˆÌÞ`ÕÀˆ˜}vœœÜ‡Õ«°˜>``ˆÌˆœ˜] œÃ«ˆÌ>ˆâ>̈œ˜`ÕÀˆ˜} vœœÜ‡Õ«>vÌiÀÌ iˆ˜`iÝiV œV>À`ˆœ}À>« ÞÜ>ÃÀi}ˆÃÌiÀi`Ì ÀœÕ} V>ÃiÀiVœÀ` review. Finally, the occurrence of renal transplant during follow-up was recorded ȘViÌ ˆÃiÛi˜Ìˆ“«>VÌÃÈ}˜ˆwV>˜ÌÞœ˜Ì iœÕÌVœ“iœvÌ iÃi«>̈i˜Ìð Statistical analysis Categorical variables were presented as numbers and percentages and Vœ˜Ìˆ˜ÕœÕÃÛ>Àˆ>LiÃ>ÃÌ i“i>˜´ÃÌ>˜`>À``iۈ>̈œ˜° œ˜Ìˆ˜ÕœÕÃÛ>Àˆ>Lià without a normal distribution were presented as the median and interquartile. 23.

(86) Chapter 2. À>˜}i­+,®°*>̈i˜ÌÃÜiÀi`ˆÛˆ`i`ˆ˜ÌœÌܜ}ÀœÕ«Ã\6-€£x°Ó¯>˜`6- ć£x°Ó¯° >Ìi}œÀˆV>Û>Àˆ>LiÃÜiÀiVœ“«>Ài`LiÌÜii˜Ì i}ÀœÕ«ÃÕȘ}Ì i V ˆ‡ÃµÕ>ÀiÌiÃÌœÀˆÃ iÀ½ÃiÝ>VÌÌiÃÌ>˜`Vœ˜Ìˆ˜ÕœÕÃÛ>Àˆ>LiÃÜiÀiVœ“«>Ài` LiÌÜii˜ Ì i }ÀœÕ«Ã ÕȘ} Ì i -ÌÕ`i˜Ì½Ã /‡ÌiÃÌ œÀ >˜˜‡7 ˆÌ˜iÞ 1‡ÌiÃÌ] >à appropriate. Correlations between continuous variables were tested with the *i>ÀܘVœÀÀi>̈œ˜ÌiÃÌ°/œiÝ«œÀiÌ iˆ˜`i«i˜`i˜ÌVœÀÀi>ÌiÃœvÀi`ÕVi`6 ÃÞÃ̜ˆVv՘V̈œ˜­6-ć£x°Ó¯®]“Տ̈Û>Àˆ>ÌiLˆ˜>Àޏœ}ˆÃ̈VÀi}ÀiÃȜ˜Ü>à applied. Cumulative event-free survival rates for the composite endpoint of >‡V>ÕÃi“œÀÌ>ˆÌÞ>˜` œÃ«ˆÌ>ˆâ>̈œ˜>˜`>‡V>ÕÃi“œÀÌ>ˆÌÞ>œ˜iÜiÀi calculated using the Kaplan-Meier method. Comparisons between patients with 6-€£x°Ó¯>˜`«>̈i˜ÌÃÜˆÌ 6-ć£x°Ó¯ÜiÀi«iÀvœÀ“i`L>Ãi`œ˜Ì i œ}‡À>˜ŽÌiÃÌ°1˜ˆÛ>Àˆ>Li>˜`“Տ̈Û>Àˆ>Li œÝ«Àœ«œÀ̈œ˜> >â>À`>˜>ÞÃià ÜiÀi«iÀvœÀ“i`̜iÛ>Õ>ÌiÌ iˆ˜`i«i˜`i˜Ì>ÃÜVˆ>̈œ˜LiÌÜii˜6->˜` Ì iVœ“«œÃˆÌii˜`«œˆ˜Ìœv>‡V>ÕÃi“œÀÌ>ˆÌÞ>˜` œÃ«ˆÌ>ˆâ>̈œ˜°ƂӇÈ`i` *Û>Õiœvä°äxÜ>ÃVœ˜Ãˆ`iÀi`̜LiÃÌ>̈Ã̈V>ÞÈ}˜ˆwV>˜Ì°-Ì>̈Ã̈V>>˜>ÞÃià ÜiÀi«iÀvœÀ“i`ÕȘ}Ì i-*--ÜvÌÜ>Ài­6iÀȜ˜Óä°ä°ƂÀ“œ˜Ž] 9\  œÀ«®°. Figure 1.*ÀiÛ>i˜ViœvivÌÛi˜ÌÀˆVՏ>À­6®ÃÞÃ̜ˆV`ÞÃv՘V̈œ˜L>Ãi`œ˜6}œL>œ˜}ˆÌÕ`ˆ˜>ÃÌÀ>ˆ˜­-®Û>Õić£x°Ó¯ˆ˜«Ài‡`ˆ>ÞÈÃ>˜``ˆ>ÞÈë>̈i˜ÌÃÜˆÌ «ÀiÃiÀÛi`6 iiV̈œ˜vÀ>V̈œ˜­6 ®°

(87) iëˆÌi6 Ĉxä¯]ÎÓ¯œv«>̈i˜ÌÃà œÜi`6ÃÞÃ̜ˆV`ÞÃv՘V̈œ˜>VVœÀ`ˆ˜}̜ÃÌÀ>ˆ˜>˜>ÞÈð Ý>“«iÃœvÌܜ«>̈i˜ÌÃÜˆÌ >˜`ÜˆÌ œÕÌ6ÃÞÃ̜ˆV `ÞÃv՘V̈œ˜>Àià œÜ˜ˆ˜Ì iœÜiÀ«>˜iÃ\`iëˆÌi >ۈ˜}Ì iÃ>“i6 ]Ì i«>̈i˜Ìˆ˜ Ì iivÌ >ÃÃiÛiÀiÞÀi`ÕVi`6-]Ü ˆiÌ i«>̈i˜Ìˆ˜Ì iÀˆ} Ìà œÜØœÀ“>6-°. 24.

(88) Impaired LV GLS in CKD and preserved LVEF. RESULTS Patient population "vÓää«Ài‡`ˆ>ÞÈÃ>˜``ˆ>ÞÈë>̈i˜ÌíÈx¯“i˜]“i>˜>}iÈä´£{Þi>ÀîÜˆÌ  6 Ĉxä¯]£ÎÈ­Èn¯® >`6-€£x°Ó¯>˜`È{­ÎÓ¯®à œÜi`6-ć£x°Ó¯ ­ˆ}ÕÀi£®°*>̈i˜ÌÃÜˆÌ 6-ć£x°Ó¯ >`“œÀi>`Û>˜Vi` 

(89) ]à œÀÌiÀ`ˆ>ÞÈà vintage, higher heart rate and higher prevalence of associated comorbidities Vœ“«>Ài`̜«>̈i˜ÌÃÜˆÌ 6-€£x°Ó¯­/>Li£®°ÕÀÌ iÀ“œÀi]«>̈i˜ÌÃÜˆÌ  6-ć£x°Ó¯ >`> ˆ} iÀÕÃiœvœÀ>>˜ÌˆVœ>}Տ>̈œ˜>˜`œÜiÀ>LՓˆ˜iÛi Vœ“«>Ài`̜«>̈i˜ÌÃÜˆÌ 6-€£x°Ó¯­/>Li£®° "˜iV œV>À`ˆœ}À>« Þ]«>̈i˜ÌÃÜˆÌ 6-ć£x°Ó¯ >`Ì ˆVŽiÀˆ˜ÌiÀÛi˜ÌÀˆVՏ>À Ãi«ÌՓ>˜`«œÃÌiÀˆœÀÜ>>˜`>À}iÀ6“>ÃȘ`iÝVœ“«>Ài`̜«>̈i˜ÌÃÜˆÌ 6 -€£x°Ó¯°6i˜`‡ÃÞÃ̜ˆV`ˆ>“iÌiÀ>˜`ۜÕ“iÜiÀi>À}iÀˆ˜«>̈i˜ÌÃÜˆÌ 6 -ć£x°Ó¯Vœ“«>Ài`̜«>̈i˜ÌÃÜˆÌ 6-€£x°Ó¯°ƂëiÀˆ˜VÕȜ˜VÀˆÌiÀˆ> >«>̈i˜Ìà >`6 Ĉxä¯] œÜiÛiÀ«>̈i˜ÌÃÜˆÌ 6-ć£x°Ó¯à œÜi`œÜiÀ 6 Vœ“«>Ài`̜«>̈i˜ÌÃÜˆÌ 6-€£x°Ó¯­È£¯ÛðÈx¯ÀiëiV̈ÛiÞ®° >ÀÞ `ˆ>Ã̜ˆV“ˆÌÀ>>˜˜Õ>ÀÛiœVˆÌÞ­ ½®Ü>ÏœÜiÀ>˜`6wˆ˜}«ÀiÃÃÕÀiÃÜiÀi ˆ} iÀ ˆ˜«>̈i˜ÌÃÜˆÌ 6-ć£x°Ó¯Vœ“«>Ài`̜Ì iˆÀVœÕ˜ÌiÀ«>ÀÌí/>LiÓ®° 6CDNG Characteristics of pre-dialysis and dialysis patients with preserved left ventricular iiV̈œ˜vÀ>V̈œ˜>˜`ivÌÛi˜ÌÀˆVՏ>À­6®}œL>œ˜}ˆÌÕ`ˆ˜>ÃÌÀ>ˆ˜­-®ć£x°Ó¯ÛiÀÃÕà 6-€£x°Ó¯ 6>Àˆ>Li. 6-€£x°Ó¯ ­˜r£ÎÈ®. 6-ć£x°Ó¯ ­˜rÈ{®. P value. Clinical characteristics: Ƃ}i­Þi>Àî. xn´£Î. ÈÓ´£{. 0.107. Male gender. n{­ÈÓ¯®. {x­Ç䯮. 0.239.

(90) ˆ>ÞÈíÛð«Ài‡`ˆ>ÞÈî. {ä­Ó™¯®. ÎέxÓ¯®. 0.002.

(91) ˆ>ÞÈÃÌÞ«i­ i“œ`ˆ>ÞÈîI. ә­Çί®. ÓÇ­nÓ¯®. 0.349.

(92) ˆ>ÞÈÃۈ˜Ì>}i­`>ÞîI. £nx­n™‡ÎÇn®. nÇ­xä‡ÓÓx®. 0.040. 1ÌÀ>wÌÀ>̈œ˜À>Ìi­“É ÉŽ}®›. x°n­£°È‡n°£®. Ç°ä­Î°™‡£ä°£®. 0.252.

(93) iÌ>- *­““}®›. {°£´£Ç. ä°{´ÓÓ. 0.545. Renal transplantation future. ÈÇ­{™¯®. ÓÈ­{£¯®. 0.253. i>ÀÌÀ>Ìi­Li>ÌëiÀ“ˆ˜ÕÌi®. Çä´£{. Çx´£{. 0.023. -ÞÃ̜ˆVLœœ`«ÀiÃÃÕÀi­““}®. £ÎÇ´£™. £{£´ÓÎ. 0.265.

(94) ˆ>Ã̜ˆVLœœ`«ÀiÃÃÕÀi­““}®. Ǚ´£ä. ÇÇ´£Î. 0.400. œ`Þ“>ÃȘ`iÝ­Ž}ɓԮ. Óx´{. Óx´x. 0.635. £­£¯®. έx¯®. 0.103. 9ƂV>ÃÇ6. 25.

(95) Chapter 2 6CDNG Continued 6>Àˆ>Li. 6-€£x°Ó¯ ­˜r£ÎÈ®. 6-ć£x°Ó¯ ­˜rÈ{®. P value. Smoker. nÇ­Èȯ®. Îx­xǯ®. 0.253. Diabetes mellitus. ә­Ó£¯®. Óä­Î£¯®. 0.128. Hypertension. ££n­nǯ®. xέnί®. 0.459. Hypercholesterolemia. xä­Îǯ®. ÓέÎȯ®. 0.910. Previous myocardial infarction. ££­n¯®. Óä­Î£¯®. <0.001. *ÀiۈœÕà Ƃ É* . £È­£Ó¯®. Ó£­Îί®. <0.001. ™­Ç¯®. £È­Óx¯®. <0.001. £Î­£ä¯®. ™­£{¯®. 0.342. Peripheral artery disease ƂÌÀˆ>wLÀˆ>̈œ˜ Medications: Diuretics. nέÈί®. {Ó­Èȯ®. 0.757. Ƃ ˆ˜ ˆLˆÌœÀÉƂ,. nx­Èx¯®. Îx­xx¯®. 0.169. B-blocker. ș­xί®. Î{­xί®. 0.953. Calcium antagonist. È{­{™¯®. ÓέÎȯ®. 0.088. Statin. ș­xί®. În­x™¯®. 0.377. Antiplatelet. ÎÇ­Ón¯®. Óx­Î™¯®. 0.128. "À>>˜ÌˆVœ>}Տ>̈œ˜. £n­£{¯®. £Ç­Óǯ®. 0.028. Ç­x¯®. Ç­££¯®. 0.235. x°n­Ó°{‡n°È®. x°Î­{°£‡Ç°x®. 0.703. Nitrates Laboratory results: ,,­“É“ˆ˜É£°ÇΓԮI i, 

(96) ‡ *­“ɓˆ˜É£°ÇΓԮa. Ài>̈˜ˆ˜i­Õ“œÉ®a 1Ài>­““œÉ®. £n´Ç. £n´Ç. 0.942. ÎÓä´££{. Σ™´££Ç. 0.968. Ó£´È. ÓÓ´n. 0.553. œÀÀiVÌi`V>VˆÕ“­““œÉ®. Ó°Ó´ä°£. Ӱδä°Ó. 0.240. * œÃ« >Ìi­““œÉ®. £°{´ä°Î. £°{´ä°{. 0.633. *>À>Ì ÞÀœˆ` œÀ“œ˜i­«“œÉ®. £x­Ç‡Óx®. £Î­™‡Óx®. 0.847. ƂLՓˆ˜­}É®. {Ó´È. Ι´È. 0.001. ÕVœÃi­““œÉ®. È´Ó. Ç´Î. 0.238. 

(97) ‡V œiÃÌiÀœ­““œÉ®. Ó°x´£°Î. Ӱδ£°ä. 0.192. i“œ}œLˆ˜­““œÉ®. Ç°Ó´䰙. Ç°Ó´£°£. 0.916. Ii>ÃÕÀi`œ˜Þˆ˜`ˆ>ÞÈë>̈i˜Ìð›i>ÃÕÀi`œ˜Þˆ˜ i“œ`ˆ>ÞÈë>̈i˜Ìðai>ÃÕÀi` œ˜Þˆ˜«Ài‡`ˆ>ÞÈë>̈i˜ÌðƂ ]>˜}ˆœÌi˜Ãˆ˜‡Vœ˜ÛiÀ̈˜}i˜âޓiÆƂ, ]>˜}ˆœÌi˜Ãˆ˜ ÀiVi«ÌœÀLœVŽiÀÆ Ƃ ]VœÀœ˜>ÀÞ>ÀÌiÀÞLÞ«>ÃÃ}À>vÌÆ 

(98) ‡ *]V Àœ˜ˆVŽˆ`˜iÞ`ˆÃi>Ãi i«ˆ`i“ˆœœ}ÞVœ>LœÀ>̈œ˜Æi,]iÃ̈“>Ìi`}œ“iÀՏ>ÀwÌÀ>̈œ˜À>ÌiÆ

(99) ]œÜ‡`i˜ÃˆÌÞ lipoprotein; NYHA, New York Heart Association; PCI, percutaneous coronary intervention; RRF, residual renal function; SBP, systolic blood pressure. Continuous data are presented >Ói>˜´-

(100) œÀ“i`ˆ>˜­ˆ˜ÌiÀµÕ>À̈iÀ>˜}i®° >Ìi}œÀˆV>`>Ì>>Ài«ÀiÃi˜Ìi`>ØՓLiÀà and percentages.. 26.

(101) Impaired LV GLS in CKD and preserved LVEF 6CDNG  Echocardiographic characteristics of pre-dialysis and dialysis patients with «ÀiÃiÀÛi`ivÌÛi˜ÌÀˆVՏ>ÀiiV̈œ˜vÀ>V̈œ˜>˜`ivÌÛi˜ÌÀˆVՏ>À­6®}œL>œ˜}ˆÌÕ`ˆ˜> ÃÌÀ>ˆ˜­-®ć£x°Ó¯ÛiÀÃÕÃ6-€£x°Ó¯ 6>Àˆ>Li. 6-€£x°Ó¯ ­˜r£ÎÈ®. 6-ć£x°Ó¯ ­˜rÈ{®. P value. 6-/`­““®. £ä´Ó. £Ó´Î. <0.001. *7/`­““®. £ä´Ó. ££´Ó. 0.003. 6

(102)

(103) ­““®. xä´Ç. x£´Ç. 0.145. £ä£´Ó{. £Ó™´{È. <0.001. 6 -

(104) ­““®. Σ´È. Îδn. 0.025. 6

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