Disclosures L. Brent Mitchell, MD Industry Disclosures Study - - PowerPoint PPT Presentation

Disclosures – L. Brent Mitchell, MD

Industry Disclosures Study Disclosures

• Guidant
• Medtronic
• St. Jude
• Cambridge Heart
• General Electric
• AVID
• CIDS
• MUSTT
• SCD-HeFT
• DINAMIT
• RAFT

No ICD ICD No CRT

medical treatment ICD

CRT

CRT pacemaker CRT defibrillator

ICDs and CRTs for Dummies

Available Platforms

No ICD ICD No CRT

medical treatment ICD

CRT

CRT pacemaker CRT defibrillator

ICDs and CRTs for Dummies

Available Platforms

Mirowski M et al. N Engl J Med 303:322-4, 1980

The Implantable Defibrillator – Michel Mirowski (1980)

ICDs and CRTs for Dummies

ICDs and CRTs for Dummies

FILTER Potential ICD Patients Higher SCD Risk Lower SCD Risk

ICDs and CRTs for Dummies

Risk Stratification for ICD

Modified from Myerburg et al Ann Intern Med 119:1187-1197, 1993

10 20 30 40

Overall ASHD risk Factors Manifest ASHD EF <0.35 VT/VF survivor

Events/year (%) 100 200 300 Events/year (thousands)

ICDs and CRTs for Dummies

Sudden Cardiac Death

In meta-analysis of secondary prevention trials of ICD therapy versus medical therapy in patients with prior life-threatening ventricular tachyarrhythmias, use of the ICD is associated with a reduction in all-cause mortality of: 1. 10%

• 2. 20%
• 3. 30%
• 4. 50%

Touch Pad Question 1

ICDs and CRTs for Dummies

ICDs and CRTs for Dummies

0.5 1 1.5 2 RELATIVE RISK

STUDY N RR

AVID 1016 0.62 (0.47-0.81) CIDS 659 0.82 (0.61-1.10) CASH 191 0.83 (0.52-1.33) OVERALL 1866 0.73 (0.59-0.89)

Connolly et al: Eur Heart J 21:2071, 2000

All-Cause Mortality – ICD versus Amio

10 20 30 40 50 60 1 2 3 4 5 Years % Mortality

Amio ICD

LVEF > 35% 10 20 30 40 50 60 1 2 3 4 5 Years % Mortality LVEF  35%

Amio ICD

Secondary Prevention ICDs – Effect of LVEF

Connolly et al. Eur Heart J 21:2071-78, 2000

ICDs and CRTs for Dummies

Modified from Myerburg et al Ann Intern Med 119:1187-1197, 1993

10 20 30 40

Overall ASHD risk Factors Manifest ASHD EF <0.35 VT/VF survivor

Events/year (%) 100 200 300 Events/year (thousands)

ICDs and CRTs for Dummies

Sudden Cardiac Death

All-Cause Mortality - ICD versus Control

Nanthakumar et al. J Am Coll Cardiol 44:2166-72, 2004

STUDY N RR

MADIT 196 0.41 (0.26 – 0.69) CABG –PATCH 900 1.08 (0.84 – 1.39) MUSTT 514 0.46 (0.34 – 0.62) CAT* 104 2.16 (0.46 – 10.22) MADIT – II 1232 0.71 (0.55 – 0.92) AMIOVIRT 103 0.92 (0.51 – 1.66) COMPANION 903 0.57 (0.40 – 0.81) DEFINITE 458 0.65 (0.40 – 1.09) DINAMIT 674 1.08 (0.76 – 1.55) SCD-HeFT 1676 0.77 (0.62 – 0.96) All Trials 7253 0.76 (0.63 – 0.91)

0.4 0.2 0.6 0.8 1.0 1.4 1.2 1.6

RELATIVE RISK

heterogeneity p = 0.0005

ICDs and CRTs for Dummies

No ICD ICD No CRT

medical treatment ICD

CRT

CRT pacemaker CRT defibrillator

ICDs and CRTs for Dummies

Available Platforms

10 Trials 0.76 (0.63-0.91)

ICDs and CRTs for Dummies

Who Should Receive an ICD?

Patients at a annual risk of sudden death that exceeds the hazard of having an ICD Provided that the patient agrees with the goal of preventing sudden death Preferably in a scenario where use of the ICD has been proven effective in an RCT

No ICD ICD No CRT

medical treatment ICD

CRT

CRT pacemaker CRT defibrillator

ICDs and CRTs for Dummies

Available Platforms

Cardiac Dyssynchrony

Effects of Abnormal Activation Sequences

• atrioventricular asynchrony
• negative LA - LV: LA contraction against closed MV
• long LA - LV: late diastolic MR decreases LV filling time
• interventricular asynchrony
• decreased LV filling time
• septum recruited to RV ejection
• intraventricular asynchrony
• some LV contraction before aortic valve opening
• some LV contraction after aortic valve closure
• wasted work stretching noncontracting regions
• uncoordinated papillary muscles leads to MR
• decreased diastolic LV filling time
• intramural asynchrony
• contraction is non-transmural

STUDY N RR

MUSTIC SR 58 3.00 (0.13 – 70.7) MUSTIC AF 43 2.19 (0.09 – 50.9) MIRACLE 453 0.74 (0.36 – 1.53) COMPANION 925 0.85 (0.66 – 1.09) CARE HF 813 0.67 (0.53 – 0.86) All Trials 2292 0.76 (0.64 – 0.90)

RAFT Investigators

0.4 0.2 0.6 0.8 1.0 1.4 1.2 1.6

RELATIVE RISK

All-Cause Mortality – CRT vs Control Class III/IV Pts

ICDs and CRTs for Dummies

No ICD ICD No CRT

medical treatment ICD

CRT

CRT pacemaker CRT defibrillator

ICDs and CRTs for Dummies

Available Platforms

5 Trials 0.76 (0.64-0.90)

ICDs and CRTs for Dummies

Who Should Receive CRT?

Patients with symptomatic CHF, low LVEF and evidence of contractile dys-synchrony Unfortunately, at present, CRT response

• ccurs in only 2/3 treated patients

CRT is often associated with reversal of adverse LV remodelling (importance?)

No ICD ICD No CRT

medical treatment ICD

CRT

CRT pacemaker CRT defibrillator

ICDs and CRTs for Dummies

Available Platforms

0.5 1 1.5 2 HAZARD RATIO

STUDY N HR

COMPANION 903 0.64 (0.48-0.86)

Bristow MR et al: N Engl J Med 350:2140-50, 2004

ICDs and CRTs for Dummies

All-Cause Mortality – CRT-D versus Med Rx

No ICD ICD No CRT

medical treatment ICD

CRT

CRT pacemaker CRT defibrillator

ICDs and CRTs for Dummies

Available Platforms

STUDY N RR MIRACLE ICD II 186 1.19 (0.17-8.26) CONTAK CD 490 0.69 (0.33-1.45) MIRACLE ICD 474 0.66 (0.39-1.11) All Trials 1150 0.69 (0.45-1.04)

RAFT Investigators

0.5 1 1.5 2 RELATIVE RISK

ICDs and CRTs for Dummies

All-Cause Mortality – CRT versus CRT-D

No ICD ICD No CRT

medical treatment ICD

CRT

CRT pacemaker CRT defibrillator

ICDs and CRTs for Dummies

Available Platforms

3 Trials 0.69 (0.45-1.04)

No ICD ICD No CRT

medical treatment ICD

CRT

CRT pacemaker CRT defibrillator

ICDs and CRTs for Dummies

Available Platforms

10 Trials 0.76 (0.63-0.91) 5 Trials 0.76 (0.64-0.90) 3 Trials 0.69 (0.45-1.04)

No ICD ICD No CRT

medical treatment ICD

CRT

CRT pacemaker CRT defibrillator

ICDs and CRTs for Dummies

Available Platforms

?

Multicentre Automatic Defibrillator Implantation Trial – Cardiac Resynchronization Therapy (MADIT - CRT)

COMPARISON: composite of all-cause mortality and HF events comparing ICD with CRT versus ICD only on background of optimal medical Rx PATIENTS: ischemic (NYHA Class I or II) CCM or nonischemic (NYHA Class II) CCM LVEF ≤ 0.30, QRSd ≥ 0.13 sec in sinus rhythm for whom ICD is planned DESIGN: double-blind, randomized, parallel-group clinical trial target 1820 patients, 3:2 randomization designed as sequential monitoring trial

Moss AJ et al. N Engl J Med 361:xxx-xxx, 2009

Primary outcome – CHF event / all-cause mortality

10 20 40 30 Cumulative Incidence 1 2 3 4 Years of Follow-up ICD CRT-ICD

HR = 0.75 (95% CI: 0.62 – 0.91) p = 0.003

Multicentre Automatic Defibrillator Implantation Trial – Cardiac Resynchronization Therapy (MADIT - CRT)

Moss AJ et al. N Engl J Med 361:1329-38, 2009

COMPARISON: composite of total mortality / CHF hospitalization comparing pts receiving a CRT ICD to those receiving an ICD alone PATIENTS: planned 1800 pts with Class II / III CHF (only Class II after Feb 2006) with an indication for an ICD and LVEF ≤ 0.30 and QRSd ≥ 0.12 (≥ 0.20 if paced) on

• ptimal medical therapy

DESIGN: “double-blind”, parallel-group RCT (1:1) 85% power for 25% RRR from 11% control rate

Resynchronization in Ambulatory Heart Failure (RAFT)

Tang AS et al. N Engl J Med 363:2385-95, 2010

Resynchronization in Ambulatory Heart Failure (RAFT)

Tang AS et al. N Engl J Med 363:2385-95, 2010

Primary outcome – CHF hospitalization / mortality

10 20 40 50 30 Cumulative Incidence 1 2 3 4 6 Years of Follow-up 5 60 ICD CRT-ICD

HR = 0.75 (95% CI: 0.64 – 0.87) p < 0.001

Resynchronization in Ambulatory Heart Failure (RAFT)

Tang AS et al. N Engl J Med 363:2385-95, 2010

Secondary outcome – all-cause mortality

10 20 40 50 30 Cumulative Incidence 1 2 3 4 6 Years of Follow-up 5 ICD CRT-ICD

HR = 0.75 (95% CI: 0.62 – 0.91) p = 0.003

Resynchronization in Ambulatory Heart Failure (RAFT)

Subgroup Analysis

permanent AF / AFL sinus / atrial paced QRSd < 150 ms QRSd ≥ 150 ms QRSd paced ≥ 200 ms LBBB RBBB IVCD PACED LVEF < 0.20 LVEF ≥ 0.20

CRT – ICD better ICD better 0.4 0.2 0.6 0.8 1.0 1.4 1.2 1.6 1.8 2.0

HR

Tang ASL et al. N Engl J Med 363:2385-95, 2010

p = 0.14 p = 0.003 p = 0.046 p = 0.05

ICDs and CRTs for Dummies

Who Should Receive CRT - Defibrillator?

Patients with symptomatic CHF, low LVEF and evidence of contractile dys-synchrony that have an annual risk of sudden death that exceeds the hazard of having an ICD Provided that the patient agrees with the goal of preventing sudden death and understands that symptom improvement

• ccurs in only 2/3 treated patients

Preferably in a scenario where use of CRT- ICD has been proven effective in an RCT

ICDs and CRTs for Dummies

With Or Without an Atrial Lead?

In the absence of a current or anticipated indication for brady pacing, ICD only pts are best treated with a VVI - ICD AV resynchronization is an important part

• f cardiac resynchronization; CRT only

pts are best treated with atrio-biV CRT Similarily, CRT-D pts are best treated with an atrio-biVentricular device

“In conclusion, this patient is being discharged from the hospital after presenting with a severe idiopathic dilated cardiomyopathy, congestive heart failure, and an LVEF of 0.22. While in hospital he was seen by EP (Dr. Mitchell) who declined to provide the patient with an CRT defibrillator. Instead, he wants the patient to be reassessed in three months time. I hope he does not die of in the interim.”

ICDs and CRTs for Dummies

When?

Secondary Prevention - Class I Indications

1. Cardiac arrest due to VF or VT not due to a transient or reversible cause. (Level of Evidence: A) 2. Spontaneous sustained VT in association with structural heart disease. whether hemodynamically stable or unstable (Level of Evidence: B) 3. Syncope of undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at EPS (Level of Evidence: B)

ICD Implantation ACC/AHA/HRS (2008)

Secondary Prevention - Class IIa Indications

1. Syncope of undetermined origin in pts with significant LV dysfunction and nonischemic dilated cardiomyopathy (Level of Evidence: C) 2. Sustained VT in pts with normal or near-normal LV function (Level of Evidence: C)

Primary Prevention - Class I Indications

1. LVEF ≤ 0.35 due to prior MI who are at least 40 days post-MI and are in NYHA Class II or III. (Level of Evidence: A) 2. LVEF ≤ 0.30 due to prior MI who are at least 40 days post-MI and are in NYHA Class I. (Level of Evidence: A) 3. LVEF ≤ 0.40 due to prior MI with nonsustained VT and with inducible VF or sustained VT at electrophysiologic study. (Level of Evidence B) 4. LVEF ≤ 0.35 due to nonischemic dilated cardiomyopathy who are in NYHA Class II or III. (Level of Evidence: B)

ICD Implantation ACC/AHA/HRS (2008)

Primary Prevention - Class IIa Indications

1. Non-hospitalized patients awaiting cardiac transplantation (Level of Evidence: C) 2. Uncommon cardiac conditions with risk factors for sudden cardiac death. (Level of Evidence: B or C)

Secondary Prevention - Class III Indications

1. Notwithstanding indications an ICD is not indicated for patients with no reasonable expectation of survival with acceptable function for one year. (Level of Evidence: C) 2. Pts with incessant VT / VF. (Level of Evidence: C) 3. Pts with significant psychiatric illnesses that may be aggravated by an ICD

• r that may preclude device follow-up. (Level of Evidence: C)

4. Pts with Class IV CHF symptoms who are not candidates for cardiac transplantation or CRT-D. (Level of evidence C)

ICD Implantation ACC/AHA/HRS (2008)

Class I Indications

1. Cardiac arrest due to VF or VT not due to a transient or reversible cause. (Level of Evidence: A) 2. Spontaneous sustained VT in association with structural heart disease. (Level of Evidence: B) 3. Syncope of undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at EPS when drug therapy is ineffective, not tolerated, or not preferred. (Level of Evidence: B) 4. Spontaneous sustained VT in patients who do not have structural heart disease that is not amenable to other treatments. (Level of Evidence: B) 5. Patients with ischemic heart disease ± mild to moderate CHF symptoms and LVEF ≤ 0.30, measured at least one month post-MI and 3 months post

• revascularization. (Level of Evidence: A)

ICD Implantation CCS Consensus (2004)

Class IIa Indications

1. Patients with ischemic heart disease and LVEF 0.31 – 0.35 measured at least

• ne month post-MI and three months post-revascularization with inducible

VF / sustained VT at EPS (Level of Evidence: B) 2. Patients with non-ischemic cardiomyopathy ≥ 9 months, LVEF ≤ 0.30, and NYHA Class II-III CHF. (Level of Evidence: B) 3. Patients with familial or inherited conditions such as but not limited to long QT syndrome, hypertrophic cardiomyopathy, Brugada syndrome, or ARVD, and at high risk for life-threatening tachyarrhythmias. (Level of Evidence B)

ICD Implantation CCS Consensus (2004)

Class IIb Indications

1. Patients with ischemic heart disease, prior MI, LVEF 0.31 – 0.35 with either no inducible VF / sust VT at EPS, or without an EPS. (Level of Evidence C) 2. Patients with non-ischemic cardiomyopathy ≥ nine months, LVEF 0.31 – 0.35 and NYHA Class II-III CHF. (Level of Evidence C) 3. Severe symptoms (e.g. syncope) attributable to sustained VT/VF while awaiting cardiac transplantation. (Level of evidence C)

ICD Implantation CCS Consensus (2004)

Class III Indications

1. Syncope of undetermined cause in a patient without structural heart

• disease. (Level of Evidence: C)

2. Incessant VT / VF (Level of Evidence: C) 3. VT / VF due to a transient or reversible disorder (e.g. AMI, electrolyte imbalance, trauma) or VT amenable to surgical catheter ablation (e.g. RV

• utflow tract VT, idiopathic LV VT) (Level of Evidence: C)

ICD Implantation CCS Consensus (2004)