Renale denervatie Ontzenuwd? Nationaal Hypertensie Congres Vrijdag 7 februari 2014 Michiel Voskuil
Hype?
Animatie Simplicity
Simulatie cathlab
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=>*?./@/)>$ABC$8.9%&.$D./+/@&.$E7927&* $ Klinisch bewijs: Simplicity programma Enrollment Complete / In Follow Up Symplicity HTN-1
Series of Non-randomised Pilot Studies n =153
3 yr
Symplicity HTN-2
Randomised Controlled Trial (1:1) n = 106
2 yr
Enrolling / Planning SYMPLICITY HTN-3 SYMPLICITY HF
Randomised Controlled Trial (2:1), n=530 Feasibility Study n=40
Global SYMPLICITY Registry Prospective Registry n=5,000 Symplicity HTN-Japan Symplicity HTN-4 Symplicity HTN-India
Randomised Controlled Trial (1:1) n=100
Completed Enroll Enroll Enroll
Randomised Controlled Trial (2:1) n= 530+
Plan
Single-arm Trial n= 40
Plan
Klinisch bewijs: EnligHTN #$%#"
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•
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• AD!$"/)M$'M&*$@9+)79.$9L$;XT$?)'<$)9$6#*9+')7&)#$=&L#)>$O$FP@&@>$/+$A#'/')&+)$ G!C3$Y$>#&7$L9..9"5J?$ • A#'J.)'$JN./S#6$)9$'J??97)$R=$EZ[$&+6$?79U/6#$G#&.)M$F@9+9*/@$#U/6#+@#$L97$ F+./2G!C*#+),$V&+6*&7($A&+69*/S#6$!7/&.$ 7#/*%J7'#*#+)$ • A&+69*/S#6$H+)#7+&N9+&.$!7/&.$)9$#')&%./'M$=&L#)>$&+6$ Fa#@NU#+#''$9L$)M#$F+./2G!C$=>')#*3$A#6J@N9+$/+$DW$#U#+)'$
Symplicity HTN-1; 36 maanden FU
F=D$QT0Y$
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Symplicity HTN-1; nierfunctie FU Mean ± SD
Na+ (mmol/L)
K+ (mmol/L)
SCr (μmol/L)
eGFR (mL/min/1.73m2)
Baseline
140.4 ± 3.9 (143)
4.1 ± 0.6 (145)
83.8 ± 20.1
83.6 ±19.7
3 Months
140.4 ± 3.1
(145) 82.6 ±21.0
6 Months
(125) 140.5 ± 3.2
4.1 ± 0.5 (125)
(143) 85.8 ± 22.6 (132) 85.2 ± 20.1
(132) 82.6 ± 20.9
12 Months
(136) 140.1 ± 3.3
(142) 85.4 ± 19.8
(142) 81.8 ± 19.5
4.1 ± 0.4 (43)
(130) 92.9 ± 29.8 (43)
(130) 76.8 ± 22.8 (43)
4.2 ± 0.9 (29)
92.0± 32.5 (28)
74.3 ± 28.0 (29)
24 Months
(130) 139.9 ± 3.0 (43)
36 Months
139.7 ± 243 (29)
F=D$QT0Y$
4.1 ± 0.4 (136) 4.0 ± 0.4 (129)
Symplicity HTN-2; SBP 30 mmd FU 6m Primary Endpoint Randomization Control Crossover† 12m post procedure
18m post procedure
24m post procedure
mm Hg
6m post procedure
6m post randomization
F=D$QT0Y$
12m post randomization
18m post randomization
24m post randomization
30m post randomization
Global Simplicity Registry; 149 sites >
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Global Simplicity Registry; ABPM f$04T$
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Relatie ABPM – office RR
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Simplicity HTN-3 design
Persbericht Medtronic – donderdag 9 januari 2014
.., failed to meet its primary efficacy endpoint. The trial met its primary safety endpoint, !
Gevolgen • =J'?#+6$=lZEVHDH!l$G!C54$/+$)M#$R<=
')#*$\=)$cJ6#$&.7#&6>$')9??#6$F+./2M)+$HW^$ • D9+N+J#$)M#$8.9%&.$=lZEVHDH!l$?9')5*&7(#)$'J7U#/..&+@#$7#2/')7>$$ • D9+N+J#$7#+&.$6#+#7U&N9+$')J6/#'$#U&.J&N+2$9)M#7$+9+5 M>?#7)#+'/9+$/+6/@&N9+'$ • D9+N+J#$/+U#'N2&)97$/+/N&)#6$')J6/#'$ • EJ%./@&N9+$7#'J.)'$[DD$QT04$\QX5Y0$*&&7)K$n&'M/+2)9+^$
Major issues remaining! • E&No+)#+$'#.#@N#$ • B#U/@#$2#7#.&)##76#$S&(#+$ • Z#N+2$#a#@)$?79@#6J7#$
Varkenscyclus! Waarneming
inductie
evaluatie (falsificatie / verificatie
Resultaat
Hypothese
deductie
Toetsing / experiment
Voorspelling
Sympathisch zenuwstelsel – bloeddruk
epM*K$Z<$#)$&.<$C&)$A#U$D&76/9.$QT0Y30T,41;q4b1$
Samenvatting concept RDN • A#+&.#$\&a#7#+)#^$'>*?&)M/'@M#$S#+J"#+$S/r+$%#)79((#+$/+$U#7'@M/..#+6#$ U97*#+$U&+$M>?#7)#+'/#$ • A#+&.#$6#+#7U&N#$?&')$/+$MJ/6/2#$/6##$U&+$?&)M9L>'/9.92/#3$?#7@J)&+#$ 7#+&.#$6#+#7U&N#$/'$U997&.$)#@M+9.92/'@M#$/++9U&N#$ • [..##+$6&)&$\G!C50$#+$Q$`K$G!C5Y$5^$"&)$%#)7#s$#a#@NU/)#/)$/+$)M#7&?/#$ 7#'/')#+)#$M>?#7)#+'/#$ • =>*?&)M/'@M#$M>?#7&@NU/)#/)$'?##.)$99($79.$/+$&+6#7#$S/#()#%##.6#+,$ M&7t&.#+K$@M79+/'@M#$+/#7S/#()#K$9%#'/)&'$g*#)&%99.$'>+6799*$g$)>?#$HH$ BZK$#)@$!$79.$ABCu$
Goede patiënten selectie • A#'/')#+)#$M>?#7)#+'/#$ – =>')9./'@M#$%.9#667J($9?$?9./$f01T$**$G2$ – f$Y$)>?#+$&+NM>?#7)#+'/U&$\`$6/J7#N@J*^$ – 4-FT+0/+"N*/")//+"'/N*?-F/"*?&)M>,$f$QT*Vg*/+g0?#7)#+'/#$\[eEZw^$#+$J/)'.J/)#+$'#@J+6&/7#$ 997S&(#+$ =>*?./@/)>$G!C50$H+U#'N2&)97'<$G>?#7)#+'/9+<$QT003;b,X005X0b3$=>*?./@/)>$G!C5Q$H+U#'N2&)97'<$V&+@#)<$QT0T3Yb1,0XTY50XTX$
• Investigator initiated study (PI Peter Blankestijn, UMCU) • Financial support by: – ZonMw – Unrestricted grant Medtronic
• Intervention financed by health insurance (“conditional reimbursement”), so far only applicable for Medtronic device • Meeting at CVZ 20 Jan 2014: expanding conditional reimbursement to other device(s)?
• ZJ.N5@#+)#7$7&+69*/S#6$@9+)79..#6$)7/&.$ 2 RDN + standard medication
1
:
Standard medication
$$ $$ • [email protected]'/9+$9L$YTT5;TT$?&N#+)'<$ • E&7N@/?&N9+$9L$Q1$BJ)@M$@#+)#7'<$
• =)J6>$')&7)#6$Z&>$QT0Y$
Objectives .294'2,"-KL+M7N+!" • ABC$7#6J@#'$eEK$&66#6$)9$J'J&.$@&7#K$@9*?&7#6$)9$J'J&.$@&7#$&.9+#K$&''#''#6$%>$[eEZ$ J+,";+M-()'2,"-KL+M7N+;!" • Fa#@)$9L$ABC$9+$)M#$J'#$9L$eE5.9"#7/+2$&2#+)'$$ • !M#$#a#@)$9L$ABC$/+$6/a#7#+)$'J%279J?',$$ – &@79''$')7&)&$9L$#8IA$\#8IA$QT51T$*Vg*/+$&+6$#8IAx1T$*Vg*/+$?#7$0$9L$./L#<$
In- and exclusion criteria O(M6P;9-("M29:+29'$ • H+6/U/6J&.$M&'$&$*#&+$6&>5N*#$=eE$f$0Y;$**G2K$&'$6#)#7*/+#6$"/)M$)M#$J'#$9L$[eEZK$"M/.#$)M#$ ?&N#+)$J'#'$Y$97$*97#$&+NM>?#7)#+'/U#$&2#+)'$L97$&)$.#&')$Y$*9+)M'$?7/97$)9$/[email protected]'/9+<$ • H+6/U/6J&.$/'$f0:$>#&7'$9L$&2#<$ @QM6P;9-("M29:+29'$ • H+6/U/6J&.$M&'$&$)7#&)&%.#$'#@9+6&7>$@&J'#$9L$M>?#7)#+'/9+$ • H+6/U/6J&.$M&'$&+$#8IA$%#.9"$QT$*Vg*/+g0$&+&)9*>$)M&)$/'$/+#./2/%.#$L97$)7#&)*#+)$ • H+6/U/6J&.$M&'$&+>$'#7/9J'$*#6/@&.$@9+6/N9+K$"M/@M$/+$)M#$9?/+/9+$9L$)M#$/+U#'N2&)97K$*&>$ &6U#7'#.>$&a#@)$)M#$'&L#)>$&+6g97$#a#@NU#+#''$9L$)M#$?&7N@/?&+)$97$)M#$')J6><$ • H+6/U/6J&.$/'$@J77#+).>$#+79..#6$/+$&+9)M#7$/+U#'N2&N9+&.$67J2$97$6#U/@#$)7/&.<$
=)&)J'$9L$?&7N@/?&N+2$@#+)#7'$
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[email protected]'/9+'$?#7$@#+)#7$
SNS; multiorgaan effector
QTTb$F+@>@.9?/&$e7/)&++/@&K$/+@$
DREAMS studie Denervation of the REnal Artery in Metabolic Syndrome
z z z z z
R+;9S(,$E79'?#@N#U#K$9%'#7U&N9+#.#$L#&'/%/./)>$')J6/#$ R-+6S2-+8,$E&No+)#+$*#)$M#)$*#)&%99.$'>+6799*$$ .294'92"+9()8P(:!$H+'J./+#$2#U9#./2M#/6$ H+MP()'92"+9()8P(:!"%.9#667J(K$A[[=$&@NU/)#/)K$./?/6#+$#+$&6/?9(/+#$ O(M6P;9+"M29:+29'" z W#7M9926$+J@M)#7$2.J@9'#$\'#7J*$f;<1$**9.gV^$*#)$2#%7J/($U&+$ *&h<$0$&+N6/&%#N@J*$$ z Q45JJ7'$'>')9./'@M#$%.9#667J($xgk$0YT**G2$*#)$2#%7J/($U&+$ *&h<$0$&+NM>?#7)#+'/UJ*$ z Z/+/*&&.$0$&66/N9+##.$@7/)#7/J*$*#)&%99.$'>+6799*$ z
G>?#7)7/2.>@#7/6#*/#K$.&&2$GBV5@M9.#')#79.K$&%69*/+&.#$&6/?9'/)&'$
LVH en diastolische functie na RDN
c$[*$D9..$D&76/9.$QT0Q3;X\0T^,XT05XTX$
DIASTOLE studie Denervation of the renAl sympathetIc nerveS in hearT failure with nOrmal Lv Ejection fraction
z R+;9S(,$E79'?#@N#U#K$2#7&+69*/'##76#$')J6/#$ z R-+6S2-+8,$E&No+)#+$*#)$M#)$M&7t&.#+$*#)$+97*&.#$FI$$ z .294'92"+9()8P(:!$F@M9$?&7&*#)#7',$FgF K$[765[6$#+$./+(#7$%9#S#*$ U9.J*#$/+6#h$ z H+MP()'92"+9()8P(:!"U#/./2M#/6K$9?+&*#'$U997$GIK$Z[DFK$$ z O(M6P;9+"M29:+29'" z =>*?)9*#+$U&+$M&7t&.#+$ z C97*&.#$9L$*/.6$&%+97*&.#$'>')9./'@M#$VW$LJ+@N#$\VWFI$f;Td^$ z !#(#+#+$U&+$6/&')9./'@M#$VW$6>'LJ+@N#$ z Q4J$%.9#667J(*#N+2$2#*/66#.6${$04TgXT$**G2$
Renale flow in RDN Flow-/drukmetingen mbv combowire gedurende RDN
Z&ML9J6K$I<$#)$&.<$G>?#7)#+'/9+$1TK$40Xq4Q4$\QT0Q^$
Renale flow in RDN Flow-/drukmetingen mbv combowire gedurende RDN
Symplicity Spyral™ Multi-Electrode Renal Denervation Catheter R+;9S("T-'6"
H,4869M9:,"H8,2'6" .2-)PM:"U+':P2+;"
A#6J@#$?79@#6J7&.$N*#$"M/.#$*&/+)&/+/+2$'/*/.&7$@./+/@&.$9J)@9*#'$ &+6$7#&''J7&+@#$9L$'J@@#''$@9*?&7#6$)9$97/2/+&.$&+6$?79U#+$ =>*?./@/)>$I.#h™$D&)M#)#7$ " 0$*/+J)#$&%.&N9+$@>@.#$ " 4$#.#@)796#'K$/+6#?#+6#+).>$'#.#@)&%.#$ " 1I$2J/6#$@&)M#)#7$@9*?&N%.#$ " C9+59@@.J'/U#$ " C&)J7&.$@9+L97*&%/./)>$
Symplicity Spyral™ Multi-Electrode Renal Denervation Catheter • • •
Fa#@NU#$/+$Y5:$**j$6/&*#)#7$7#+&.$ &7)#7/#'$ m+#$'/S#$v)'$*9')$ =/*/.&7$&%.&N9+$?&|#7+$)9$=>*?./@/)>$I.#h$
*Feasibility study was conducted in patients with vessel diameter of 4-8 mm
Patiënt voorbeeld z E&No+)#K$4:$r&&7$ z W9972#'@M/#6#+/',$*/27&/+#K$6>'./?/6#*/#K$QT0T,$M>?#7)#+'/#$ z Vm,$$ q C/#)$S/#(#$?&No+)#<$V,$0<1T*K$8,$bY(2K$%J/(9*U&+2$XQ<;@*$ q e.9#667J($7#@M)',$04Yg0TY3$./+(',$0Y:g0TT$ z Q45JJ7'$AA,$2#*/66#.6,$04;gX4$**G2$ z V&%,$2.J@9'#,$b<0$**9.gVK$@7#&N+/+#,$10$}*9.gV$$ z [@)J#.#$*#6/@&N#,$?#7/+69?7/.$066$4*2K$#S#)79.$066$0T*2$ z =@7##+/+2'?79)9@9.,$2##+$'#@J+6/&/7#$997S&(#+$g$2#'@M/()#$&+&)9*/#$
Patiënt voorbeeld; MRI
Patiënt voorbeeld; Ao angio
Rechts
Geschikt: • Geen stenoses • Diameter " 4mm
Links
Selectief; zenuwbanen rondom a renalis z -9*#+$U&+&L$_$!0T5VQ$ z W9.2#+$&$A#+&./'$+&&7$6#$+/#7$ z V/22#+$U997&.$/+$&6U#+NN&$
Patiënt voorbeeld
Patiënt voorbeeld
Patiënt voorbeeld; epicrise z W9#.)$S/@M$%#)#7K$9+)'?&++#+$ z [eEZ,$8#*/66#.6,$0Q;g:4$**G2K$GA$bbg*/+$ z ZAH$0$r&&7,$2##+$+/#7&7)#7/#')#+9'#$ z V&%,$
Patiënt voorbeeld; epicrise
Take home messages • Renale denervatie is veelbelovende behandeling voor sympaticus gedreven ziektebeelden • Procedure is eenvoudig en veilig • Effect zeer variabel: meting succes procedure?! • HTN-3: echt negatief / causa? Sympathy! • Studies naar RDN bij andere ziektebeelden onderweg; nieuwe ontwikkelingen catheters (multiple electrodes, radialis)
Take home messages • $A#+&.#$6#+#7U&N#$/'$U##.%#.9U#+6#$%#M&+6#./+2$U997$'>*?&N@J'$ 2#67#U#+$S/#()#%##.6#+$ • $E79@#6J7#$/'$##+U9J6/2$#+$U#/./2$ • $Fa#@)$U&7/&%#.,$*#N+2$'J@@#'$?79@#6J7#uw$ • $G!C5Y,$#@M)$+#2&N#L$g$@&J'&u$=>*?&)M>w$ • $=)J6/#'$+&&7$ABC$%/r$U#7'@M/..#+6#$S/#()#%##.6#+$\9&$M&7t&.#+K$ /+'J./+#$7#'/')#+N#^$9+6#7"#2$$ • C/#J"#$9+)"/((#./+2#+$@&)M#)#7'$\*J.N?.#$#.#@)796#'K$7&6/&./'^$
Vasculaire geneeskunde Wilko Spiering Frank Visseren Cardiologie Willemien Verloop Martine Beeftink Lisette Hubens Michiel Voskuil Pieter Doevendans
Klinische anatomie Ronald Bleys
Nefrologie Eva Vink Rosa de Jager Esther de Beus Jaap Joles Peter Blankestijn
Interventieradiologie Evert-Jan Vonken Willem Mali
Nucleaire geneeskunde Asbjorn Scholtens
Radiologie Tim Leiner Birgitta Velthuis
Animatie
