Resincronizzazione cardiaca: opportunità sospinta anche dalle … · 2018-03-29 ·...

Resincronizzazione cardiaca: opportunità sospinta anche dalle nuove

tecnologie?

Davide Giorgi, MD

U.O. Cardiologia

Elettrofisiologia e Cardiostimolazione

P.O. San Luca

Lucca (Italy)

La CRT Oggi: efficace e riconosciuta…

Ponikowski P, Voors AA & al.

2016 ESC GL acute & chronic HF. Eur Heart J 2016 May

Indicazione di classe I / II (a-b) in pz HF-sintomatici con:

- terapia medica ottimale

- LVEF ridotta

- dissincronia elettrica (QRS>130ms)

… ma ci sono ancora molti NON-Responder

Daubert JC & al. Heart Rhythm 2012 (CRT consensus document)

45%

20%

Daubert JC & al. Eur Heart J 2016;

doi:10.1093/eurheartj/ehw270

Come ridurre la non risposta alla CRT?

AccurataSELEZIONE PZ.

• Aderenza alle Linee Guida

• Tecniche di Imaging

• Valutazione Comorbidità

• Nuovi parametri ECG

PersonalizzareProcedura

d’IMPIANTO

• Assesment pre-impianto

• Valutazione aree Scar

• Aree attivazione tardiva

• Morfologia

• Quadripolare vs bipolare

• Endo LV / MSP / MPP

Personalizzare

Programmazione post-IMPIANTO

• Metodi ECO-guidati

• Tecniche non invasive

• Funzioni DEVICE-based:

• STATICHE

• AUTOMATICHE

Fattore di non riposta: aderenza alle LG

▪Tra 30-40% dei pazienti non riceve trattamenti basati su evidenze

scientifiche

▪ Tra 20-25% dei pazienti riceve trattamenti non necessari o addirittura dannosi

Una sintesi di tutte le principali

LG internazionali, compresa la

valutazione costo-efficacia

NICE

G.Boriani et al., HFC 13, 2017, 117-137

Stratificazione la prognosi del paziente:

lo score EAARN

Kathib et al., European Journal of Heart Failure (2014) 16, 802–809

Score EAARN: 608 pz.; follow up 10 anni

Per statificare la prognosi dei pazienti candidati alla CRT.

EAARN: EF<22%; Age >70 anni; AF; Renal Disf. GDR<60 mL/min/1.73m2; NYHA IV

“In our view, an EAARN score ≥3

should not be an absolute

contraindication, because the

score does not include

symptomatic benefits of CRT. It

may, however, help physicians

to individualize CRT therapy.

Furthermore, it highlights the need

to start the therapy at the earliest

stages of disease, avoiding if

possible the implant of CRT

devices in patients with very

advanced heart disease and

systemic involvement”

• Durata LVAT max (tempo di attivazione LV)

• Vettorcardiografia: QRSarea (indicatore ritardo LV) QRSarea > 69μVs predittore risposta

Selezione del paziente: E’ davvero sufficiente il

solo QRS?LBBB valutato attraverso ECG: parametro molto specifico (funziona), ma poco

sensibile (come predittore di risposta)

Nuove proposte:

• Misure Echo standard

• Echo speckle tracking difficoltà riproduzione risultati con software diversi (standardizzazione)

Selezione del paziente tramite imaging

Everdingen et al., Cardiovasc Ultrasound. 2017 Oct 18;15(1):25. Doltra et al.Volume 7, Issue 10, October 2014, Pages 969-979

Non accordo su possibilità di stratificazione pz attraverso valutazione dissincronia

meccanica per imaging (studio Prospect)

Problema: non standardizzazione delle misure

Echo speckle tracking

Technology evolution in CRT can help in reducing the rate of NR

1. Accurate SELECTIONof candidate Pts

2. IMPLANT customization

3. CRT SettingsOptimization during

POST-IMPLANT

IndicationEtiologyMorphologyStructureClinical history……

• Sarebbe opportuno un mappaggio cardiaco completo difficile esecuzione

• Ritardo Q-LV solo pochi punti misurabili, info troppo parziale /poco pratica?

• Strategia di mezzo: mappaggio elettroanatomico coronarico intra-proceduraletramite NAVX

Selezione ramo target, come personalizzare il

pacing? - 1

Engels et al. J. of Cardiovasc. Trans. Res. (2016) 9:257–265

• Body surface Activation Mapping (BSAM, non invasiva)

• Parametro: SDAT (deviazione standard delle attivazioni)

• SDAT si riduce del 20% con stimolazione BIV vs basale

• Ulteriore riduzione del 26% nel ramo target (tutte eziologie dei pz.)

• Pazienti con LBBB e QRS>150 ↑ SDAT basale ↑ riduzione SDAT

Selezione ramo target, come personalizzare il

pacing? - 2

Modalità di stimolazione: Nuovi approcci alla CRT…

MSP would appear be one way of potentially overcoming NR in addition to other novel pacing techniques (i.e. LV endocardial)

Rinaldi CA & al. A review of MSP to achieve CRT. Europace 2015

TRANS-SEPTAL orTRANS-APICAL

+ Miglior terapia di pacing+ Attivazione LV fisiologica+ minor stimolazione frenico+ liberta di scelta del sito LVp

- Tecnica non semplice- Necessità di OAT - pochi dati a lungo termine(safety / efficacy)

Approccio TRANSVENOSO Approccio Endocardico

Evoluzione della terapia CRT

LV1-RV (@ t0)

LV2-RV (@ t1)

BIP LV 4P LV 4P LV+ MPP

BIVp (RV+LV1):

• 1 LV vector (non-progr.)

• 1 among few LV vectors

• Ritardo RV-LV progr.

BIVp (RV+LV1):

• 1 among many LV vect.

• Progr. RV-LV delay

MPP (RV + 2 LV vectors)

• 2 among many LV vect.

• Progr. RV-LV delay• LV1-LV2 sequential• LV1-LV2 simultaneous

Una “CRT-multisito” può essere ottenuta in modi

diversi…

with a single LV lead or more leads …

Rinaldi CA & al. A review of MSP to achieve CRT. Europace 2015

In-LINEresynchronization

1 RV lead + 1 4P LV lead

Between-AREAsresynchronization

1 RV lead + 1 LV lead+

1 lead (RV or LV)

Multi-Area-Pacing in CRT dedicated technologies

…CRT-D systemmodified header with 3 V ports

• SKIPS using Y-ADAPTORS• ALLOWS hypothetical TriV configur.:

• Dual-site LV

• Dual-site RV

Dual-site LV

(1RV+2LV)

Dual-site RV

(2RV+1LV)

Multi-Point LV pacing• UNIFORM and FASTER activation front

• BY-PASS of SCAR regions (reduces conduction delays

between electrically disconnected regions)

Author/Journal Size Method Comparison Outcome FU

Gutleben KCDSTM 2012

N = 59 Ao-VTI MPP vs. BiV+QuickOpt

Ao-VTI ACUTE + M1

Pappone CHFSA 2013

N = 43 LVEF, LVESV, NYHA MPP vs. BiV LVEF, LVESV, NYHA ACUTE + M3

Rinaldi AJCF 2013

N = 52 Safety+ Ts-SD(12 LV segments)

MPP vs. BiV OK safety;Dyssynchrony

ACUTE

Thibault BEuropace 2013

N = 21 LV dP/dt MPP vs. BiV LV dP/dt ACUTE

Pappone CHR 2014

N = 44 PV loop(dP/dt, SW, SV, EF)

MPP vs. BiV All param. ACUTE

Rinaldi AJICE 2014

N = 40 Strain-echoLVOT-VTI

MPP vs. BiV All param. ACUTE

MP LVp ACUTELY improves the

hemodynamic performance

1717

STUDIO MPP-IDE, MULTICENTRICO; N = 381 PZ RANDOMIZZATI (1:1) BIV VS. MPP

Una stimolazione LV Multi-Point « mirata »migliora il tasso di responder (vs. BiV)

Bi-V arm MPP arm

70%

100%

25%

75%

29.9%

70.1%

Endpoint primario di efficacia1

Non-inferiority

Tasso di

Non

responder

Tasso di

Responder

La stimolazione LV MP con un ritardo minimo tra i 2 vettori

di stimolazione LV ha fornito il miglior tasso di risposta1

1. Tomassoni GF.et al. Late-Breaking Clinical Trials I, LBCT01-03 - Safety and efficacy of Multipoint

Pacing in Cardiac Resynchronization Therapy: The MultiPoint Pacing (MPP) IDE Study. Presented

at Heart Rhythm 2016 - 05/05/16.

< 30 mm SpacialSeparation (n=115)

≥ 30 mm Spatial Separation & > 5 ms Timing Delay

(n=32)

≥ 30 mm Spatial Separation & 5 ms

Timing Delay (n=52)

63%

87%

69%

Analisi ancillare1

Tasso di risposta nei sottogr. del

braccio MPP

60%

100%

Zanon F & al. MPP by a LV 4P lead improves the acute hemodynamic response to CRT compared with conventional BiVp at any site.

Heart Rhythm 2015

ACUTE effects of MP LVpn = 29 pts - mean age 72 yrs NYHA II/III: 17%/83%

Ischemic CMP 62% Mean EF 29% - mean QRS 183ms

LBBB 66%, RBBB 21%, IVCD 7% PM-dependant 7%

All pts, all veinsWORST site (dP/dt)

BEST site (dP/dt)

Zanon F & al. Optimization of LVp site plus MPP improves remodeling and clinical response to CRT at 1 year. Heart Rhythm 2016

MP LVp: mid & long-term OUTCOMES

bip LV lead bip or 4P LV lead +

LV site optim.

4P LV lead +

LV site optim +

MPP ON

Hemod. / Clinical Response @ 1Y FU:1. ESVi: delta-LVESV>15%

2. NYHA: delta > -1 class

3. Packer: death / HFH / NYHA > -1

Multi-Point LVp “AMPLIFIES” the

hemodynamic and clinical response to CRT

n = 110 CRT-D pts

CRT3P-MPP

Umar F et al. Europace 2016;18:1227-34

A novel approach for

CRT in ISCHEMIC pts

with extensive scar

New frontiers of MP LVp:

ISCHEMIC PTS

Proprietary and confidential — do not distribute

2012First MPP device

implanted in Italy

MPP Experience : esperienza

1475 pazienti arruolati!

10 studi in acuto - 239 pz

5 studi in cronico - 936 pz

L’elettrocatetere: Quartet™

Dimensioni

47 mm

30 mm

20 mm

Lunghezze (cm) 75, 86, 92

Diametro esterno (F) 4,7 F corpo, 4 F sezione distale

Introduttore 5 F (lume interno)

1. Punta distale 1: D1

2. Medio 2: M2

3. Medio 3: M3

4. Prossimale 4: P4

Dimensioni nominali connettore SJ4-LLLL (mm);

20mm

10mm

17mm

95o

110oAnatomy targets for “Double-Bend” Quartet™

LV LEAD

This shape may be useful for medium sized vessels rather than larger vessels that require greater fixation.

Anatomy targets for “Small-S” Quartet™ LV

Lead

The smaller shape may be best for shorter vessels that can accommodate the entire curve

20 mm10 mm

10 mm vs 17 mm

8 mm

(Vs 16 mm)

Anatomy targets on “wide-spaced” Quartet™

LV LEAD

This shape and spacing may be best for longer vessels that can accommodate the large S-curve and all electrodes.

20 mm

27mm (vs 10 mm)

13 mm

(vs 17 mm)16 mm

L’elettrocatetere: Quartet™Benefici

P4

M3

M2

D1

Ridurre la necessità direintervento/revisione chirurgica

Offrire opzioni per la gestione di PNS e altre soglie di stimolazione

Garantire la scelta del miglior sito distimolazione senza comprometterela stabilità dell’elettrodo

Diminuire i costi per ospedalizzazionie revisione chirurgica vs Bipolare

MultiPointTM PacingMultiPoint™ pacing delivers two pulses from the Quartet™ LV lead per pacing cycle, resulting in a more uniform ventricular contraction

• Allows LV first or RV first

• Delays between pulses are programmable

Confronto tra stimolazione da un singolo dipoloe una linea di dipoli– propagazione longitudinale

Convex excitation front Flat excitation front

La stimolazione da un singolo dipolo produce un fronte d’onda più lento del 15% rispetto a una linea di dipoli

IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 42, NO. 10, OCTOBER 1995

Concept of Multipoint Pacing: Early Experimental Evidence

Muscle bundle with horizontal fiber orientation

Spach MS, et al. Circ Res. 1982;50:175 -191

nonuniform conduction, slow activation, delay of ± 15 ms between 1 - 4

single point

pacing

simultaneous

multipoint

pacing

uniform conduction, faster activation, virtually no delay between 1 - 4

1234

1234

1

2

3

4

1

2

3

4

30

MultiPoint Pacing

La stimolazione multisito è

basata sul concetto di stimolare e

catturare un volume maggiore di

muscolo ventricolare e di

generare fronti d’onda piatti

Questo risulta in un tempo di

conduzione più veloce e migliora

la sincronia e la funzione

cardiaca

▪ Cattura un’area più ampia

▪ Arruola le aree attorno alle

cicatrici

▪ Migliora il pattern di

depolarizzazione e

ripolarizzazione

▪ Migliora i parametri

emodinamici in acuto/cronico

▪ Migliora la resincronizzazione

LBBB patients with longer RV-LV activation delay at CRT implantation had greater improvement in NT-proBNP, EF, and significantly better clinical outcome1

Reduction of risk of HF

hospitalization or death

for RV-LV delay ≥ 86 ms56%

Kosztin M. et al. Europace Journal, June 2015 (n=125)1

Reduction of risk of HF

hospitalization or death

for RV-LV delay ≥ 86 ms

and LBBB77%

1. Kosztin M. et al. Longer right to left ventricular activation delay at cardiac resynchronization therapy implantation is associated with improved clinical outcome in left

bundle branch block patients . Europace Journal, June 2015. Prospective, observational, cohort study. Patients with EF ≤ 35%, QRS ≥ 120ms and successful CRT

implantation. 2.2 years median time follow-up.

Longer RVS-LVS interval at pacing site: independent predictor of CRT response?

“Apical pacing should be avoided in CRT”

72%Increased risk for

HF/death with apical pacing1

Years from randomization

Pro

bab

ilit

y o

f H

F o

r D

eath

Left Ventricular Lead Position and Clinical Outcome in MADIT-CRT Trial. Singh J. et al., Circulation, 20111

Death

or hosp

italiz

atio

n fo

r m

anagem

ent o

f HF (%

)

Months since randomization

Sites of LV lead implantation and response to CRT

observations from REVERSE trial. Thebault C et

al., European Heart Journal, 20121

73% Increased risk for

HF/death with apical pacing1

Long veins Short veins Narrow or tortuous veins

ACUITY™ X4 Spiral LACUITY™ X4 Spiral S ACUITY™ X4 Straight

The Acuity™ X4 family of LV leads offers different electrode spacing to

accommodate individual anatomy and to help you pace at your target location

ACUITY™ X4 – Effective Proximal Pacing Options

3D Spiral with Multiple Electrodes

17 Pacing Vectors

Electrical Delays to LV Lead - QLV

Inside the heartBlue lines show the spread

of electrical activation

inside the heart

Quadripolar LV

pacing lead

We can measure the electrical delay:

1. From the beginning of ventricular activation (Q point)

2. To each LV lead electrode

This is the Q-LV interval.

(e.g. for a quadripolar lead, you can measure 4 QLV values)

Q-LV interval

Surface

ECG

LV EGM

8. Gold M., et al. The relationship between ventricular electrical delay and left ventricular remodeling with cardiac resynchronization therapy. European Heart Journal. (2100) 32:2516-2524.

Electrical dyssynchrony, as measured by QLV, was strongly and independently

associated with reverse remodeling and QOL with CRT8

Example of RVS-LVS delay test results from a Rally X4 Study patient. Data on file

Boston Scientific Reference Guide for X4 CRT-D and CRT-D 359209-001 EN Europe 2013-04. AUTOGEN X4 reference guide supplement (part# 359386-001)

One additional click

for a potential lifetime benefit

VectorGuide™ is designed to quickly identify the

best of 17 vectors options based on clinically

relevant tests including RVS-LVS delay

Maximizing CRT response:VectorGuide Identify the longest RVS-LVS interval

Single Site Pacing

• Single site LV pacing: 2 ventricular pacing pulses, separated by an optional offset

• MultiSite LV Pacing: 3 ventricular pacing pulses, separated by optional offsets

MultiSite Pacing Technology Overview

LV Pace1

RV Pace

LV Offset

2

Example 1:

Offset = 0ms

Single Site Pacing


• MultiSite LV pacing: 3 ventricular pacing pulses, separated by optional offsets

LV Pace1

RV Pace

LV Offset

2

Example 2:

Offset = 40ms


MultiSite Pacing

1st

LV Pace (LVa)1

2nd

LV Pace (LVb)

RV Pace3

LVaLVb Offset

LVbRV Offset

2



Example 1:

No Offset“simultaneous pacing”


MultiSite Pacing

1st

LV Pace (LVa)1

2nd

LV Pace (LVb)

RV Pace3

LVaLVb Offset

LVbRV Offset

2



Example 2:10ms LVaLVb Offset

10ms LVbRV Offset

“sequential pacing”


4040

Tutte le case oggi propongono una soluzione MP

MPP sincro & sequenziale

216 combinazioni

MPP su un canale

5 combinazioni

MPP sincro & sequenziale

106 combinazioni

MPP sequenziale

60 combinazioni

MPP sincrono (doppio canale)

48 combinazioni

Torniamo alle Linee Guida..

L’ottimizzazione della programmazione serve?

Brignole M et al. ESC Pacing/CRT Guidelines. EHJ 2013;34:2281-329

GL ESC CRT 2013 raccomandazione “tiepida”

(in termini di beneficio clinico: ottimizzazione vs. pratica clinica standard)

Tecnologie “DEVICE-based” per ottimizzare AVD &/or VVD

Lunati M & al.

JAFIB 2014 Aug/Sep Vol.

7(2)

QuickOpt (SJM)IEGM-based

SmartDelay (BSx)

IEGM-based

STATIC optimization(during FU visit only)

SonR (LivaNova-Sorin)Hemodynamic method

Adaptive-CRT (Mdt)IEGM-based

AUTOMATIC optimiz.

(continuous over time)

SonR sensor / SonR system:

Automatic Hemodynamic Optimization1. SonR SENSORa micro-accelerometer realized

in the tip of the SonRtip RA lead.

The SonR signal correlates with

the

global myocardial contractilityMICRO-ACCELEROMETER

2. SonR SYSTEM (SonRtip + CRT-D):

able to optimize (weekly,

automatically)

AVD & VVD, at rest & under effort

The RESPOND-CRT study assessed the SAFETY

and EFFICACY of continuous SonR optimiz. of

AVD/VVD

vs. Echo AV/VV optimization at discharge

CRT Optimization Clinical Response(% Responders, Packer’s clinical combined EP)

ClinicalPractice

(NO optimiz.)

Echo or STATIC Optimization(device-based)

@ in-hospital FU

AUTOMATIC optim.(device-based),

ambulatory (continuous)

RESPOND-

CRT

(FU 12M)


DX Technology for CRTBIOTRONIK’s DX Technology provides atrial diagnostics to CRT patients without an atrial lead.

In some CRT patients,

physicians decide not to

implant an atrial lead.

Using the DX option in CRT

allows

• atrial diagnostics

• AV sinchrony during CRT

• SMART dual chamber SVT-

VT discrimination.

Advantages of two leads CRT: complications risk reduction

The risk of atrial lead complications resulting

in reinterventions was 1.3% (ICD/CRT-D),

and the risk of left ventricular lead

complications was 1.8% (CRT-D).

50 dual chamber ICD: 5 atrial lead

dislodgments, and 1 atrial lead had

to be revised because of

undersensing, event rate 12%.

DX Technology for CRT: why


Heart failure diagnostic tools and reports help you take a multifactorial approach to

treating patients—by leveraging all of these sensors at once, our reports deliver

more accurate results that help you make more informed decisions.

Daily Heart Rate

Heart Rate Variability (SDANN)

AT/AF Burden

RV Rating during AT/AF

% LV Paced

V-Therapy

Thoracic Impedance

Activity Level

Night Heart Rate

Respiratory Rate

Weight

Blood Pressure

Sleep Incline

Heart Failure Sensor Suite


• HeartLogic™ Composite Index calculated daily using:– First and third heart sounds– Thoracic impedance– Respiration rate– Ratio of respiration rate to tidal volume– Heart rate– Patient activity

• HeartLogic Index of 16 selected as nominal threshold– Higher threshold reduces sensitivity– Lower threshold increases unexplained

alerts

Average HeartLogic Index Trend in MultiSENSE

Study for Patients with and without Heart

Failure Events

Patients with HFE

Patients without HFE

Beginning 29 days pre-event

the HeartLogic Index was

higher (p<0.05) than baseline

average (180 to -90 days)1Boehmer J et al. Presented at American Heart Association 2016:

http://www.abstractsonline.com/pp8/#!/4096/presentation/60291

Heart LogicBenefit of Multifactorial Approach Validation:

The MultiSENSE Study

51

Conclusioni

▪ Nonostante la CRT sia riconosciuta come terapia efficace ed abbia un ruolo

ben preciso nelle LG HF più recenti, ancora oggi si osservano tassi elevati di

NR.

▪La tecnologie di ultima generazione possono contribuire in modo

significativo alla riduzione del tasso di NR, in particolare attraverso:

-Nuovi parametri per la selezione / stratificazione dei pazienti candidati

alla CRT

-Ottimizzazione della configurazione di pacing

-Monitoraggio dello stato emodinamico del paziente

-Ottimizzazione sistematica ed emodinamica dei parametri di

stimolazione

▪Il ruolo della stimolazione Multi Point come strumento di riduzione del tasso

di NR deve ancora essere chiarito. I moderni dispositivi ad elevata longevità,

permetteranno un utilizzo più estensivo di questa modalità di pacing.

.

Resincronizzazione cardiaca: opportunità sospinta anche dalle … · 2018-03-29 ·...

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Transcript of Resincronizzazione cardiaca: opportunità sospinta anche dalle … · 2018-03-29 ·...