R.Mantovan Cesena

"Curiosare tra le raccomandazioni delle nuove linee guida sul pacing e resincronizzazione cardiaca"

Roberto MANTOVAN, MD, PhDDepartment of Cardiology

Osp. M. Bufalini - CESENA (Italy)

Roberto MANTOVAN, MD, PhDRoberto MANTOVAN, MD, PhDDepartment of CardiologyDepartment of Cardiology

Osp. M. Bufalini Osp. M. Bufalini -- CESENA (Italy)CESENA (Italy)

R.Mantovan Cesena

R.Mantovan Cesena

Topics

1. Indications for pacing2. Indications for CRT

a) Sinus rhythmb) Atrial fibrillationc) HF and conventional pacemaker indicationd) Backup ICD in CRT

3. Indications for pacing in specific conditions

R.Mantovan Cesena

2007 Guidelines

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1. Indications for Pacing• Classification was based on etiology and now

on clinical presentation (ECG)

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1. Pacing Overview

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1. Pacing in Persistent Bradycardia

• Sinus node diseasePacing mode

New: DANPACE

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DANPACE: AAIR vs DDDR• 1,415 SSS pts. were randomized to an AAIR or

DDDR pacemaker and followed for 5.4 years• No difference in survival; AAIR group developed

more AF and had more reoperations

Nielsen JC. European Heart Journal 2011; 32: 686–696

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1. Pacing in Intermittent Documented Bradycardia

New: ISSUE III

New: ISSUE III

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ISSUE III• Inclusion: neurally mediated syncope, ≥3 episodes in

last 2 years, age >40 years• 511 pts received a Reveal; 89 had syncope and

received a PM - randomization to PM ON or OFF

Brignole M. Circulation 2012; 125: 2566-2571

p=0.04

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Undocumented Reflex Syncope and Unexplained Syncope

New: was IIa

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%60

50

40

30

20

10

00

Blanc 84

Claesson 07

Claesson 07

Menozzi 93

Crilley 97 Morley 82

0.5 1 1.5 2 2.5

Brignole 92 (a) No therapy

Pacemaker

Brignole 92 (b)

Sugrue 86

Brignole 92 (b)

3 3.5 4 Lopes 11Claesson 07

Claesson 07

Sugrue 86Walter 78 Brignole 92 (a)

Blanc 84 Stryjer 86

Years

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Undocumented Reflex Syncope and Unexplained Syncope

New: was IIa

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ISSUE 3

SYNCOPE

Syncope recurrence after PM therapy

according to tilt test response

1.00

0.90

0.80

0.70 PM, asystolic TT

0.60

0.50 PM, non-asystolic TT

0.40 log rank: p=0.53

0.30

0.20

0.10

0.00

0 3 6 9 12 15 18 21Months

Number at risk

PM TT+ Asyst 14 8 6 6 5 4 3 2PM TT+ No Asyst 12 6 4 3 3 2 1 1

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1. Pacing in Intermittent Documented Bradycardia

Pacing mode

NEW

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1. Bundle Branch BlockNew: B4

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Diagnosis, management, and outcomes of

patients with syncope and bundle branch block B4

European Heart Journal (2011) 32, 1535–1541

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1. Bundle Branch Block

New: Press

Santini M et al: Circ Arrhythm Electrophysiol. 2013;6:101-107.)

END POINT(1)syncope, (2)symptomatic presyncopal episodes associated with a device intervention (ventricular pacing), and (3)(3) symptomatic episodes associated with intermittent or permanent atrioventricular block (any degree).

R.Mantovan Cesena

Topics

1. Indications for pacing

2. Indications for CRTa) Sinus rhythmb) Atrial fibrillationc) HF and conventional pacemaker indicationd) Backup ICD in CRT

3. Indications for pacing in specific conditions

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CRT: still a “never ending story” of NR pts?

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

48%

18%

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Suboptimal CRT Response

Mullens, JACC 2009

Potential reasons for suboptimal CRT response

c

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Troubleshooting in CRT

Poole JE, Circulation 2010; 122: 1553-61

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Effects of cardiac resynchronization therapy on disease progression

“Effects of cardiac resynchronization therapy on disease progression in chronic heart failure” Erwan Donal, Christophe Leclercq, Cecilia Linde, and Jean-Claude Daubert* EHJ January 2006

R.Mantovan Cesena

Evidence based benefits CRT NYHA III-IV

COMPANION

All cause mortality or unplanned hospitalization

All cause mortality

CARE-HF

All cause mortality or unplanned hospitalization for major cardiovascular event

Bristow et al., NEJM 2004; Cleland et al, NEJM 2005

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�

Level IA

QRS > 120 ms?

Yes

No

� �EF < 35%?

Yes

No

CRT

All patients on optimal medical therapy

ESC 2008 Guidelines – CRT/CRT-DAlgoritmo a prova di scimmia!

NYHAIII/IV?

Yes

No

Level IA

CRT-D

Dickstein et al. Eur Heart J 2008

Reasonable expectation

of survival >1 year?

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Il sonno della ragione genera mostri

F. Goya

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ESC Guidelines 2010 (devices in HF)

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Evidence based benefits CRT NYHA II

RAFT

REVERSE (24 mos)

MADIT CRT

Statistically significant interactions:� QRS duration, p=0.003 favoring

intrinsic QRS≥150 ms;� QRS morphology, p=0.046 favoring

LBBB .

Combined endpoint: Death or HF hospitalization

Linde C et al. Am Heart J 2006;151: 288–294.Moss AJ et al. N Engl J Med. 2009;361(14):1329-38.Tang AS. N Engl J Med 2010

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ESC Guidelines 2010 (devices in HF)

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Effectiveness of Cardiac Resynchronization Therapy byQRS Morphology in the Multicenter Automatic Defibri llator Implantation Trial–

Cardiac Resynchronization Therapy (MADIT-CRT)Circulation. 2011;123:1061-1072.)

• No clinical benefit was observed in patients with a non-LBBB QRS pattern (right bundle-branch block or intraventricular conduction disturbances)

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Madit-crtRaft

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CompanionCare-HF?

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• Because these severely symptomatic patients have much to gain and because there was no subgroup of patients that clearly did not benefit from CRT, individuals in NYHA functional class III and IV have been given the broadest indication for CRT.

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2a. CRT in Sinus Rhythm

NEW

NEW

NEW

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HF, EF < 35%, QRS > 120 ms

• Female gender

•• LBBBLBBB /wide QRS

• NON-isch DCMP

• Contractile reserve

• Age• NYHA IV• A-Fib• COPD• Diabetes

Probably will be SUPER responder

• Ischemic etiology– Scar– Ischemia

• Pulm. HT• Chronic

Renal dysf.• Narrow qrs

Probably will NOT respond

Correct clinical choice

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ESC Guidelines 2013

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2a. CRT in Sinus Rhythm - Pacing Mode

• Similar to EHRA/HRS consensus statement

Daubert JC. EHRA/HRS Consensus Statement. Europace 2012; 14: 1236–1286

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% BiV Pacing and Outcome

• Analysis of survival of 36,935 patients followed by remote monitoring (Latitude)

• Highest survival if % BiV pacing is above 98%, both for patients with and without AF

Survival by median %BiV pacing and AFSurvival per quartile % BiV pacing

Hayes DL. Heart Rhythm 2011; 8: 1469-1475

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The higher % of pacing is mandatory in resychronization therapy

Otimal AV delay either at rest or during effortWith the technical improvement of recent CRT devices and appropriate fine-tuning of devices with specific algorithms designed to improve CRT delivery, we can reasonably expect that the relatively high number of partial or complete non-responders will decrease.

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2b. CRT in Persistent AF

New: was IIb

New: was IIb

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2b. CRT in Persistent AF

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% of CRT during AF?

• All patients received digoxin, beta-blockers, and amiodarone for rate control; device interrogation showed 90% BiV pacing.

• Only 9 (47%) patients had effective pacing.

• Long-term respondersto CRT had a significantly higher percentage of fully pacedthan nonresponders.

• Conclusions Pacing counters overestimate the degree of effective BIV pacing

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�Four year survival in 1285 patients undergoing cardiac resynchronization therapy (CRT): The importance of at rioventricular junction ablation By M. Gasparini (World congress Sept 2-6 2006, Barcelona)

�Study in 4 Centers, FU 24 Months�1285 patients were implanted with CRT devices from August 1995 to August 2005�1042 pts were in sinus rhythm (SR) and 243 (19%) patients AF. �AFabl group: patients was achieved either by ablating the atrioventricular junction (AVJ) in 118 pts�AFnoabl group: patients prescribing chronotropic-negative drugs in 125 pts

Conclusions: In patients with AF undergoing CRT, AVJ ablation significantly reduces long-term all-cause mortality rate.

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2c. CRT in PM Upgrades or PM Indication with Reduced EF

1. Many small studies: Results comparable to De novo CRT

2. Clinical perspective:A strategy of initially conventional anti-brady pacing, with later upgrade in case of worsening symptoms seems reasonable.

New: Block HF

New: was IIa

R.Mantovan CesenaPoole et al Complications With Pacemaker and ICD Re placements, Circulation. 2010;122:1553-1561.)

Major complications occurred in 15.3% of 713 cohort 2 patients. transvenous lead addition for replacement or upgrade

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2c. CRT in PM Upgrades or PM Indication with Reduced EF

New: Block HF

New: was IIa

R.Mantovan CesenaN engl j med 368;17 nejm.org april 25, 2013

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BLOCK HF: Study Design• Comparison between CRT ON and OFF in

AV block

CRT ON

• AV block• EF ≤50%• NYHA Class I-III

Enrolmentn=918

RandomisationDouble-blindedn=691

Primary end point:Time to first event

(all cause mortality, HF urgent care, ≥15% increase in LVESVi)

Follow-up

CRT OFF

®

12 m.

1:1ON vs OFF

24 m.

Curtis AB. J Cardiovasc Electrophysiol 2007; 18: 965-971

Enrollment: December 2003 – November 2011

CRT implant

30-60 d.

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Primary Endpoint Results: Mortality/HF Urgent Care/LVESVI

Curtis AB. N Engl J Med 2013; 368: 1585-1593

Hazard ratio: 0.74 (0.60 - 0.90)

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Clinical Components of Primary Endpoint: Mortality/HF Urgent Care Visits

Curtis AB. N Engl J Med 2013; 368: 1585-1593

Hazard ratio: 0.73 (0.57 - 0.92)

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Note: Table below includes pre-randomization AE’s

Number of Adverse Events (N, % of Subjects)

CRT-P CRT-D

BiV (N=243) RV (N=241) BiV (N=106) RV (N=101)

Procedure-related Complications 50 (41, 17%) 32 (25, 10%) 18 (18, 17%) 21 (16, 16%)

System-related Complications*Generator-relatedLV lead-related

41 (36, 15%)10 (10, 4%)16 (15, 6%)

37 (31, 13%)11 (11, 5%)13 (13, 5%)

48 (40, 38%)32 (32, 30%)

6 (6, 6%)

34 (24, 24%)13 (12, 12%)10 (9, 9%)

* Subcategories for other system-related complicati ons such as RA or RV-related complications not incl uded

Adverse Events

Curtis AB. N Engl J Med 2013; 368: 1585-1593

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RAFT trial

During the first 30 days after device implantation, there were 118 device-or implantation-related complications among the 888 patients receiving

ICD–CRT, as compared with 61 of 898 patients in the ICD group (P<0.001)

ICD group CRT-D group

Hemo/Pneumothorax 8 (0.9%) 11 (1.2%)

Pocket hematoma 11 (1.2%) 14(1.6%)

Device/Pocket infection

16 (1.8%) 21 (2.4%)

Lead dislodgement 20 (2.2%) 61 (6.9%)

CS dissection 0 11 (1.2%)

Tang A SL, N Engl J Med 2010

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2d. CRT with concomitant ICDTable 17

No recommendation concerning CRT-D or -P

R.Mantovan Cesena

Topics

1. Indications for pacing2. Indications for CRT

a) Sinus rhythmb) Atrial fibrillationc) HF and conventional pacemaker indicationd) Backup ICD in CRT

3. Indications for pacing in specific conditions

R.Mantovan Cesena

3. Special Indications• Pacing as a treatment for Atrial

Fibrillation

NEW

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MRI in patients with implantedcardiac devices

Recommendations Class Level

1) Conventional cardiac devices .

In patients with conventional cardiac devices, MRI at 1.5 T can beperformed with a low risk of complications if appro priate precautionsare taken (see additional advice).

IIb B

2) MRI-conditional PM systems .

In patients with MR-conditional PM systems, MRI at 1.5 T can be IIa Bdone safely following manufacturer instructions.

www.escardio.org/guidelinesEuropean Heart Journal2013; 34: 2281-2329

Europace2013; 15: 1070-1118

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Remote managementof arrhythmias and device

Recommendations Class Level

Device-based remote monitoring should be considered in order to

provide earlier detection of clinical problems (e.g . ventricular

tachyarrhythmias, atrial fibrillation) and technica l issues (e.g. lead

fracture, insulation defect).

IIa A

www.escardio.org/guidelinesEuropean Heart Journal2013; 34: 2281-2329

Europace2013; 15: 1070-1118

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3. Special Indications

TAVI HOCMNEW

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1. Pacing in Persistent Bradycardia

• Acquired AV blockPacing mode

NEW

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Small randomised crossovers studies (2-6 months)

comparing upgrading to CRT to RV-pacingin pts with PM indication (mostly high degree AV block)

who have heart failure NYHA III-IV and LVEF < 40%

Upgrading to CRT resulted in symptomatic improvements and

reduced hospitalisations compared RV pacing

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Controlled Studies or Survey comparingde novo CRT to upgrading to CRT (FU 3-38 M)

Upgraded pts had similar improvements as de novo CRT pts

R.Mantovan Cesena(Heart Rhythm 2009;6:468–473)

AGE Diabetes

NYHA BUN

Non sinus Rhythm

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• Multivariate Cox analysis identified five variables, age 65 years, NYHA class III–IV, diabetes, non–sinusrhythm, and increased levels of BUN, as independent risk predictors of overall mortality

(Heart Rhythm 2009;6:468–473)

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• Patients with three or more of these risk factors were characterized by a 6-year mortality rate of 68%, compared with 43% in those with one to two risk factors and 19% in patients with no risk factors.

(Heart Rhythm 2009;6:468–473)

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Predict CRT Response

Gorcsan and Prinzen, Understanding the Cardiac Substrate and the Underlying Physiology, Heart Rhythm, Vol 9, No 8S, August Supplement 2012