1. Early CRT Intervention Reduces Death and Heart Failure Events : Updated Insight from MADIT-CRT Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy .

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3. Building to the Next Question:
MADIT-II: Easier to Qualify for SCD Protection
31%
MADIT-II
Size: 1218 U.S. patients
Endpoint: All-cause mortality (patient follow-up = 20 months)
Published: NEJM 2002
Reduction in the risk of death in heart attack survivors with ICDs, when compared to conventional medical therapy (CMT) alone (p = 0.016).
Building to the Next Question:
ICD therapy in patients with chronic ischemic heart disease improved survival but were the same patients with increased risk of heart failure (HF) events.1
MADIT II: Easier to Qualify for SCD Protection
MADIT-II was a breakthrough trial in 2002 that proved prophylactic ICDs save lives in patients with a prior MI and low EF. Some of the additional data from MADIT-II pointed out that while we have the great ability to save lives from SCA – there’s also a need in many of these patients to prevent HF.
Respective 39% & 58% increase in risk of first & recurrent HF hospitalizations during follow-up.1
“These findings should direct more attention to the prevention of HF in patients who receive an ICD.”1
37 percent relative reduction in the risk of death for ICD patients at 96 months
Note to speaker: RV pacing is associated with worsening heart failure, and MADIT-II was conducted before this was well-proven. However, please note that within the Goldberg article even when RV pacing is slight – patients were still at risk of developing worsening heart failure. Quote from manuscript’s Conclusion Section: “Our findings show that the life-prolonging benefit of ICD therapy is associated with increased HF events. The augmented rate of HF after appropriate defibrillator shocks suggests that high-risk patients whose lives are saved by ICD therapy are at increased risk for subsequent HF events.” The same patients at risk of needing ICD therapy were the same patients at risk for HF events.
*Compared to CMT alone. Goldenberg I, et al. Presented 5/14/2009, HRS session.html. 1. Goldenberg I, et al. Circulation, June

4. Building to the Next Question:
SCD-HeFT: Preventing SCD in Heart Failure Patients
23%
SCD-HeFT
Size: 2521 patients in North America and New Zealand
Endpoint: All-cause mortality
Published: NEJM 2005
Reduction in the risk of all-cause mortality when using an ICD, in combination with conventional drug therapy (CDT), when compared to CDT alone (p = 0.007)
Building to the Next Question:
ICD therapy saved NYHA Class II/III patients’ lives from tachyarrhythmias – but a major cause of mortality remained: heart failure (31% of deaths, evenly distributed among treatment arms).1
SCD-HeFT – Preventing SCD in Heart Failure:
SCD-HeFT was another landmark ICD trial in 2005 that proved both ischemic and non-ischemic heart failure patients benefit from SCD protection. However, Dr. Packer’s substudy from this data clearly pointed out that while we can save their lives from tachyarrhythmias – a major cause of mortality remained HF in these Class II/III HF patients.
Mode of death substudy showed death from tachyarrhythmia was reduced by 60% in the device arm, without appreciably changing the mortality from other causes.1
1 Packer DL, Bernstein R, Wood F, et al. Impact of Amiodarone versus implantable cardioverter defibrillator therapy on the mode of death in congestive heart failure patients in the SCD-HeFT trial. Heart Rhythm. 2005;2:S38. Abstract AB20-2.

5. Building to the Next Question:
COMPANION: Providing New Access to CRT
20%
COMPANION
Size: 1520 U.S. patients
Endpoint: All-cause mortality or first hospitalization
Published: NEJM 2004
Reduction in the risk of all-cause mortality or first hospitalization with CRT-D, in combination with OPT, compared to OPT alone (p = 0.011)
Building to the Next Question:
CRT-Ds save lives in NYHA Class III/IV HF patients, but pump failure was the most common cause of death (44.4%).1
70% of HF patients are in NYHA Class I/II.2 There is a need to slow their progression to symptomatic heart failure.
COMPANION – Providing New Access to CRT:
Finally, I want to mention the COMPANION data. COMPANION proved CRT-D can save lives in late-stage HF patients (Class III-IV). But the data showed that pump failure was still the most common cause of death – urging us to want to prevent or slow any patient’s progression to this stage of symptomatic heart failure.
Speaker Note: Recommend being prepared to address the question regarding the fact that we did not see a significant reduction in pump failure death in COMPANION. Recommend pointing to the symptomatic relief, QoL, etc. that a CRT can provide an NYHA Class III/IV patient that an ICD (and even OPT) can't provide.
Please note that this slide speaks to the primary endpoint. Secondary endpoint data is included as a backup slide if you wish to use it.
Carson P, et al, JACC, 2005 Dec 20; 46(12):
O'Connell JB, Bristow MR. Economic impact of heart failure in the United States: time for a different approach. J Heart Lung Transplant Jul-Aug;13(4):S

6. Ability to save lives from sudden cardiac death…
Key Learning
Bottom Line:
MADIT II
Ability to save lives from sudden cardiac death…
SCD-HeFT
Key Learning:
Taken altogether, this sequence of successful trials taught us some key points that are now standard of care guidelines.
In MADIT-II and SCD-HeFT it was proven that these patients need and benefit from defibrillators. The ICD helped restore rhythmicity, but in the sub-analyses we learned many of these patients went on to have worsening HF.
It takes CRT to help restore contractility.
In COMPANION, late-stage heart failure patients were able to benefit from CRT-D devices because of the restoration of BOTH the rhythmicity (from the “D”) and contractility (from the CRT) in one device -- both saving and improving their lives.
But, we haven’t yet solved the issue of HF – certainly not in earlier stage HF patients.
…heart failure remains an issue
COMPANION

7. Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT)

8. Introduction
Heart failure remains a significant health concern; a heart failure event is associated with a five-fold increase in mortality in 5 years.
Cardiac resynchronization therapy with defibrillation (CRT-D) has been demonstrated to reduce mortality and hospitalizations, improve symptoms, and increase exercise capacity.
Prior to MADIT-CRT, Boston Scientific CRT-Ds were indicated by FDA for the treatment of patients with the following conditions:
Moderate to severe heart failure (NYHA Class III/IV) despite optimal pharmacological therapy
Reduced systolic function (LVEF  35%)
Wide QRS (QRS duration ≥ 120 ms)
Introduction:
As you know, heart failure remains a significant health concern; a heart failure event is associated with a five-fold increase in mortality in five years.
Cardiac resynchronization therapy with defibrillation (CRT-D) has been demonstrated in published results to reduce mortality and hospitalizations, improve symptoms, and increase exercise capacity in patients with New York Heart Association Class III/IV heart failure; thus FDA previously limited the CRT-D indication to those patients, specifically patients with:
Moderate-severe heart failure despite optimal pharmacological therapy,
Reduced systolic function (LVEF = 35%)
Wide QRS (QRS duration = 120 ms)

9. Rationale for Undertaking MADIT-CRT
Currently, patients with severe left ventricular systolic dysfunction, a wide QRS complex, and asymptomatic or mildly symptomatic heart failure are indicated for prophylactic ICD therapy without CRT
Although ICD therapy is effective for the prevention of sudden cardiac arrest, it does not slow the progression of heart failure
However, progression of heart failure in these patients is associated with increased mortality and diminished quality of life
Retrospective studies of CRT-D in NYHA Class I/II patients reported improvement in echocardiographic variables, suggesting a potential role for CRT-D earlier in the disease process
Accordingly, MADIT-CRT was undertaken to determine if early intervention with CRT-D in patients with asymptomatic or mild heart failure could reduce death and heart failure events
Rationale for Undertaking MADIT-CRT:
Patients with severe left ventricular systolic dysfunction, a wide QRS complex, and with asymptomatic or mildly symptomatic heart failure were indicated for prophylactic ICD therapy without CRT.
Although ICD therapy is effective for the prevention of sudden cardiac arrest, it does not slow the progression of heart failure, and the progression of heart failure in these patients is associated with increased mortality and diminished quality of life.
Retrospective studies of CRT-D in NYHA Class I-II patients reported improvement in echocardiographic variables, suggesting a potential role for CRT-D earlier in the disease process.
Thus, MADIT-CRT was undertaken to determine if early intervention with CRT-D in patients with asymptomatic or mild heart failure could reduce death and heart failure events.
Higgins et al, JACC (2001)- CONTAK CD
Abraham et al, Circulation (2004)- Scd HeFT
Higgins et al, JACC (2001)
Abraham et al, Circulation (2004)

10. MADIT-CRT Primary/Secondary Effectiveness Hypotheses
Primary: It was hypothesized that CRT-D would reduce the risk of the combined endpoint of all-cause mortality or heart failure event, whichever came first, when compared with ICD in patients with asymptomatic or mildly symptomatic heart failure with left ventricular dysfunction and wide QRS
A heart failure event was defined as a patient having signs and symptoms of heart failure, with either:
Intravenous decongestive therapy in an outpatient setting, or
Augmented intravenous or oral decongestive therapy during in-hospital stay
Secondary: Evaluate the effects of CRT-D, relative to ICD, on the patient-specific rates of recurrent heart failure events over the full study period
Primary and Secondary Effectiveness Hypotheses:
Primary Effectiveness Hypothesis
The primary endpoint was designed to determine if CRT-D would reduce the risk of the combined end point of all-cause mortality or heart failure event, whichever came first, when compared with ICD, in patients with asymptomatic or mildly symptomatic heart failure with left ventricular dysfunction and wide QRS.
A heart failure event (HFE) was defined as a patient having signs and symptoms of heart failure with either:
Receiving intravenous decongestive therapy (IV diuretics, IV neseritide, IV inotropes) in an outpatient setting, or
Receiving an augmented heart failure regimen with oral or intravenous therapy during in-hospital stay
Secondary End Point Hypothesis
The secondary endpoint was designed to evaluate the effects of CRT-D, relative to ICD, on the patient-specific rates of recurrent heart failure events over the full study period.
In MADIT-CRT, both the primary and secondary hypotheses were hard, objective endpoints.

11. Study Design
Designed to detect a 25% reduction in the risk of the primary end point
Wang-Tsiatis group-sequential design
95% power at a two-sided significance level of 5%
Sample size requirement of 1820 patients
Randomized controlled trial
Randomization on a 3:2 basis to CRT-D/ICD
Stratified by ischemic status and clinical center
Data analyzed on an intention-to-treat basis
Study Design:
The study was designed to detect a 25% reduction in the risk of the primary end point with CRT-D as compared to ICD, which required a sample size of 1820 patients.
MADIT-CRT was a randomized controlled trial on a 3:2 basis, CRT-D/ICD
The study was stratified by ischemic status and center, and
Data were analyzed on an intention-to-treat basis, meaning that patient data was analyzed based on how the patients were randomized.

12. Main Inclusion Criteria
Ischemic heart disease (NYHA Class I or II) or non-ischemic heart disease (NYHA Class II) for at least three months prior to entry
Optimal pharmacologic therapy
Beta blockers, ACE/ARB, and statins (ischemic patients) unless not tolerated or contraindicated
Left ventricular ejection fraction ≤ 30%
QRS duration ≥ 130 ms
Sinus rhythm
Main Inclusion Criteria:
In order to participate in MADIT-CRT, patients needed to have Ischemic heart disease (NYHA Class I or II) or non-ischemic heart disease (NYHA Class II) for at least three months prior to entry.
Patients were on optimal heart failure pharmacologic therapy: including Beta blockers, ACE/ARB, and statins (ischemic patients) unless not tolerated or contraindicated
All patients needed to have a Left ventricular ejection fraction = 30%,
A QRS duration = 130 ms, and have sinus rhythm by an ECG.

13. Main Exclusion Criteria
Currently implanted pacemaker, ICD, or CRT device
Current indication for CRT
Atrial fibrillation within one month of entry
NYHA Class III/IV within three months of entry
CABG, PCI, or MI within three months of entry
Main Exclusion Criteria:
Patients were excluded from MADIT-CRT if they were implanted with a pacemaker, ICD, or CRT device;
If they had an indication for CRT;
If they had atrial fibrillation within one month of study entry,
If they were in NYHA Class III/IV within three months of study entry, or if
They had a coronary artery bypass graft surgery (CABG), percutaneous coronary intervention (PCI) (balloon and/or stent angioplasty), or a myocardial infarction (MI) within three months of entry into the study.

14. MADIT-CRT: Methods Led by Dr. Arthur J. Moss
Largest randomized NYHA Class I/II CRT-D trial to date
Enrollment
1820 patients, 110 centers, countries
Average follow-up
34.3 months
Commercially available devices provided by Boston Scientific were used
Baseline Evaluation
To document inclusion/exclusion criteria and establish baseline heart statusa
Randomization (3:2 CRT-D:ICD)
Stratified by center and ischemic status
CRT-D + OPT
(1089 patients)
ICD + OPT
(731 patients)
Clinic Follow-up Visits
1 month post-enrollment/randomization, 3 months post-randomization, and quarterly thereafter to a common study
closure dateb
MADIT-CRT was led by Dr. Arthur J. Moss at the University of Rochester, in Rochester, New York. The largest NYHA Class I or II CRT-D trial to date, MADIT-CRT followed 1820 patients for an average of 34.3 months. The study was conducted at 110 investigational centers across 14 countries. Commercially available devices provided by Boston Scientific were used.
The study was powered to detect a 25% reduction in the risk of the primary endpoint with CRT-D, as compared to ICD. Patients were randomized on a 3 to 2 basis to either CRT-D or ICD alone. The study was stratified by ischemic status and center, and data were analyzed on an intention-to-treat basis.
aBaseline evaluation includes history and physical exam, electrocardiogram, and echocardiogram. Patients are randomized and then baseline testing is completed including BNP (US only), quality-of-life assessment, 6-minute walk test, and Holter monitor recording (CRT-D patients only).
bThe 12-month follow-up visit includes echocardiogram, BNP (US only), 6-minute walk test, Holter monitor recording (CRT-D patients only), and device interrogation. Other follow-up visits include history and physical exam, clinical events, and device interrogation. Quality-of-life assessments were conducted at 6-month intervals.
Moss AJ, et al. N Engl J Med. 2009;361: 14

15. Study Milestones Primary endpoint was met on June 22, 2009
Results were published online on Sep. 1, 2009, in the NEJM and presented as a late-breaker at ESC
Published in print in the NEJM on Oct. 1, 2009
PMA submitted to the FDA in December 2009
FDA requested updated results through Dec. 31, 2009
FDA panel took place on Mar. 18, 2010, and there was unanimous recommendation for approval of the expanded CRT-D indication for the MADIT-CRT left bundle branch block (LBBB) sub-population
Study Milestones:
The primary endpoint was met on June 22, 2009 and a press release was issued.
Dr. Moss, in conjunction with the MADIT-CRT Executive Committee, published the results in the New England Journal of Medicine on-line on September 1 and he presented the results at the European Society of Cardiology late-breaker in Barcelona, Spain.
The same results were published in print in the NEJM on October 1.
BSC submitted the pre-market application in December 2009, based on the June 22 data.
FDA then requested updated data through December 31, 2009 to determine if the results persisted over time.
The Center for Devices and Radiological Health (CDRH) Panel was scheduled on March 18, BSC and FDA presented the study results to the physician panel, and the panel voted for a unanimous approval of the expanded CRT-D indication for the MADIT-CRT left bundle branch block sub-population.
The data through December 31, 2009 supports BSC labeling and will be presented in the following slides: please keep in mind, the addition of 6 months of data explains why the results published in the NEJM and in any abstracts or manuscripts published by Dr. Moss and the Executive Committee, differ from Boston Scientific labeling.

16. Previously Published and Updated Results
34%
57%
MADIT-CRT met its endpoint in June 2009 and results were published in the September 2009 NEJM online addition.
Results showed that CRT-D was associated with a 34% reduction in the relative risk of the primary endpoint
Primary effectiveness endpoint achieved
The FDA requested to see additional 6 months of data analyzed (through December 2009)
It was subsequently discovered and validated that in the LBBB subgroup, patients received substantial benefit from CRT-D. Non-LBBB patients did not show evidence of benefit. The LBBB sub-group made up approximately 70% of the total MADIT-CRT population.
MADIT-CRT met it’s end point in June, 2009 and results were published in the September 2009 NEJM online addition
FDA requested an additional 6 months of data to see if the benefit of CRT-D persisted over time
Now this is where it get’s interesting
This data consisted of a subgroup analysis based on pre-specified clinical baseline characteristics that revealed statistically significant interactions with gender and QRS width.
During a sub-analysis investigation of benefit in female patients, a disparity in the prevalence of LBBB between women and men was discovered in which women were more likely than men to have LBBB.
The study results were then examined by LBBB and, indeed, LBBB was associated with substantially greater improvement across all endpoints as compared to the entire study population. Non-LBBB patients did not show evidence of benefit.
N Engl J Med Oct 1;361(14): Epub 2009 Sep 1. Cardiac-resynchronization therapy for the prevention of heart-failure events.
Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, Estes NA 3rd, Foster E, Greenberg H, Higgins SL, Pfeffer MA, Solomon SD, Wilber D, Zareba W; MADIT-CRT Trial Investigators.

17. Consistent Results with LBBB across Subgroups
The consistency of these results across all the pre-specified subgroups is remarkable. This whisker plot reflects the study results across all the subgroups. The dashed line corresponds with the hazard ratio for the LBBB subpopulation. Everything to the left of 1 favors CRT-D therapy. Everything to the right reflects lack of CRT-D benefit. You will notice that all the results are to the left of 1, indicating that CRT-D reduces death and first heart failure events in all patients regardless of their baseline demographics, as compared to ICD.

18. LBBB Sub-population Baseline Demographics
LBBB Baseline Demographics:
Patient characteristics were well-balanced between the groups. A comparison of the LBBB sub-population to the full population revealed that the LBBB sub-population included a greater proportion of women, a greater mix of non-ischemic patients in Class II heart failure, and a greater mean QRS width. Otherwise, there were no substantial differences between the two populations.

19. Exploratory Analysis - Hypothesis Generating Only: LBBB Echocardiographic Outcomes
One of the tertiary endpoints was based on echocardiographic outcomes. Please keep in mind that this is an exploratory analysis that is hypothesis generating only. It is compelling however. The LBBB subpopulation had a reduction in left ventricular end systolic volume of 62 ml with CRT-D, compared to a19ml reduction with ICD. Similarly, this population had a reduction in left ventricular diastolic volume of 57ml with CRT-D as compared to 15ml reduction with ICD. Additionally, a12% increase in left ventricular ejection fraction was seen with CRT-D as compared to a 3% increase with ICD in the LBBB sub-population. Please keep in mind that this is an exploratory analysis.
To speakers: While the medical community may have different interpretations as to what this echo data represents clinically, speakers cannot state, suggest, or imply that this data demonstrates any sustained or persistent structural changes (ie, reverse remodeling) with CRT therapy. Speaker's presentations and discussions are limited to the data shown here and no interpretation of this data can be made. Please conclude that this data is for hypothesis generation only.
CRT therapy was ON during echocardiographic measurements and may have influenced the results.

20. Results
In asymptomatic or mild heart failure, patients with wide QRS, LV dysfunction, and LBBB on stable optimal heart failure pharmacologic therapy, CRT-D, as compared to ICD, was significantly associated with:
An acceptable safety profile
Primary endpoint showed:
57% reduction (p < 0.001) in the risk of a composite of all-cause mortality or heart failure events. This was driven by:
35% reduction (p = 0.048) in the risk of all-cause mortality, and a
63% reduction (p < 0.001) in the risk of heart failure events
In asymptomatic or mild heart failure patients with a wide QRS, LV dysfunction, and LBBB on stable optimal heart failure pharmacologic therapy, CRT-D, as compared to ICD, was significantly associated with an acceptable safety profile.
When looking at the composite primary endpoint comprised of all-cause mortality or heart failure events, there was a relative risk reduction of 57% that was driven by a relative reduction of 35% in the risk of death and a relative reduction of 63% in the risk of heart failure events.
The secondary endpoint showed a relative reduction of 43% in the risk of recurrent heart failure events.
Secondary endpoint showed: 43% reduction (p = 0.001) in the risk of recurrent heart failure events 20 20

21. New Boston Scientific CRT-D Indication
Boston Scientific Cardiac Resynchronization Therapy Defibrillators (CRT-Ds) are indicated for patients with heart failure who receive optimal pharmacologic therapy (OPT) for heart failure and who meet any one of the following classifications:
Moderate to severe heart failure (NYHA Class III/IV) with EF ≤ 35% and QRS duration ≥ 120 ms
Left bundle branch block with QRS ≥ 130 ms, EF ≤ 30% and mild (NYHA Class II) ischemic or nonischemic heart failure or asymptomatic (NYHA Class I) ischemic heart failure
Recently, the FDA approved Boston Scientific’s expanded CRT-D indication to include patients with left bundle branch block with QRS ≥ 130 ms, EF ≤ 30% and mild (NYHA Class II) ischemic or nonischemic heart failure or asymptomatic (NYHA Class I) ischemic heart failure 21 21

22. Identification of patients
In order to successfully identify NYHA Class I and II heart failure patients most likely to benefit from CRT-D therapy, begin with an ECG analysis to screen for LBBB and a wide QRS
Identification of Patients:
In order to successfully identify NYHA Class I and II heart failure patients most likely to benefit from CRT-D therapy, begin with an ECG analysis to screen for wide QRS and LBBB.
Questions to consider for discussion with audience
Do you think you’ll find that early intervention with CRT-D will have similar effects on frequency and duration of heart failure events and hospitalizations in your patients compared to the data in MADIT-CRT?
With this new indication, are you more likely to treat patients sooner rather than later?
You may have been concerned in the past about identifying the most appropriate patients for CRT-D, how might this new indication with LBBB address that concern?
What are the top concerns of your patient when you discuss device therapy? Do those concerns interfere with the care that you would like to provide?
Are the needs of the MADIT-CRT patient different than other CRT-D patients?
How is the patient conversation different for someone receiving a CRT-D instead of the “stand by insurance policy” of an ICD?
How many NYHA Class I and II patients do you see in a week?
How many of those have LBBB and a wide QRS?

23. Thank you
Questions?

24. CRT-D Systems from Boston Scientific CRM
Indications and Usage
Boston Scientific Cardiac Resynchronization Therapy Defibrillators (CRT-Ds) are indicated for patients with heart failure who receive stable optimal pharmacologic therapy (OPT) for heart failure and who meet any one of the following classifications:
Moderate to severe heart failure (NYHA Class III-IV) with EF ≤ 35% and QRS duration ≥ 120 ms
Left bundle branch block (LBBB) with QRS ≥ 130 ms, EF ≤ 30%, and mild (NYHA Class II) ischemic or nonischemic heart failure or asymptomatic (NYHA Class I) ischemic heart failure
CONTAK RENEWAL® 3 CRT-Ds Indications and Usage: Cardiac Resynchronization Therapy Defibrillators (CRT-Ds) are indicated for patients with moderate to severe heart failure (NYHA III/IV) who remain symptomatic despite stable, optimal heart failure drug therapy, and have left ventricular dysfunction (EF  35%) and QRS duration  120 ms.
Contraindications
There are no contraindications for this device.
Warnings
Read the product labeling thoroughly before implanting the pulse generator to avoid damage to the system. Such damage can result in patient injury or death. Program the pulse generator Tachy Mode to Off during implant, explant or postmortem procedures to avoid inadvertent high voltage shocks. Always have sterile external and internal defibrillator protection available during implant. If not terminated in a timely fashion, an induced tachyarrhythmia can result in the patient's death. Ensure that an external defibrillator and medical personnel skilled in CPR are present during post-implant device testing should the patient require external rescue. Advise patients to seek medical guidance before entering environments that could adversely affect the operation of the active implantable medical device, including areas protected by a warning notice that prevents entry by patients who have a pulse generator. Do not expose a patient to MRI device scanning. Strong magnetic fields may damage the device and cause injury to the patient. Do not subject a patient with an implanted pulse generator to diathermy since diathermy may cause fibrillation, burning of the myocardium, and irreversible damage to the pulse generator because of induced currents. Do not use atrial-tracking modes in patients with chronic refractory atrial tachyarrhythmias. Tracking of atrial arrhythmias could result in VT or VF. Do not use atrial-only modes in patients with heart failure because such modes do not provide CRT. LV lead dislodgment to a position near the atria can result in atrial oversensing and LV pacing inhibition. Physicians should use medical discretion when implanting this device in patients who present with slow VT. Programming therapy for slow monomorphic VT may preclude CRT delivery at faster rates if these rates are in the tachyarrhythmia zones. Do not kink leads. Kinking leads may cause additional stress on the leads, possibly resulting in lead fracture. Do not use defibrillation patch leads with the CRT-D system, or injury to the patient may occur. Do not use this pulse generator with another pulse generator. This combination could cause pulse generator interaction resulting in patient injury or lack of therapy delivery. For specific models, when using a subpectoral implantation, place the pulse generator with the serial number facing away from the ribs. Implanting the pulse generator subpectorally with the serial number facing the ribs may cause repetitive mechanical stress to a specific area of the titanium case, potentially leading to a component failure and device malfunction.
Precautions
For information on precautions, refer to the following sections of the product labeling: clinical considerations; sterilization, storage and handling; implant and device programming; follow-up testing; explant and disposal; environmental and medical therapy hazards; hospital and medical environments; home and occupational environments. Advise patients to avoid sources of electromagnetic interference (EMI) because EMI may cause the pulse generator to deliver inappropriate therapy or inhibit appropriate therapy.
Potential Adverse Events
Potential adverse events from implantation of the CRT-D system include, but are not limited to, the following: allergic/physical/physiologic reaction, death, erosion/migration, fibrillation or other arrhythmias, lead or accessory breakage (fracture/insulation/lead tip), hematoma/seroma, inappropriate or inability to provide therapy (shocks/pacing/sensing), infection, procedure related, and component failure. Patients may develop psychological intolerance to a pulse generator system and may experience fear of shocking, fear of device failure, or imagined shocking. In rare cases severe complications or device failures can occur.
Refer to the product labeling for specific indications, contraindications, warnings/precautions and adverse events. Rx only.
(Rev. M)

25. ICD Systems from Boston Scientific CRM
ICD Indications and Usage
ICDs are intended to provide ventricular antitachycardia pacing and ventricular defibrillation for automated treatment of life-threatening ventricular arrhythmias. ICDs with atrial therapies are also intended to provide atrial antitachycardia pacing and atrial defibrillation treatment in patients who have or are at risk of developing atrial tachyarrhythmias.
Contraindications
Use of ICD systems are contraindicated in: Patients whose ventricular tachyarrhythmias may have reversible cause, such as 1) digitalis intoxication, 2) electrolyte imbalance, 3) hypoxia, or 4) sepsis, or whose ventricular tachyarrhythmias have a transient cause, such as 1) acute myocardial infarction, 2) electrocution, or 3) drowning. Patients who have a unipolar pacemaker.
Warnings
Read the product labeling thoroughly before implanting the pulse generator to avoid damage to the ICD system. Such damage can result in patient injury or death. Program the pulse generator ventricular Tachy Mode to Off during implant, explant or post-mortem procedures to avoid inadvertent high voltage shocks. Always have sterile external and internal defibrillator protection available during implant. If not terminated in a timely fashion, an induced tachyarrhythmia can result in the patient’s death. Ensure that an external defibrillator and medical personnel skilled in cardiopulmonary resuscitation (CPR) are present during post-implant device testing should the patient require external rescue. Patients should seek medical guidance before entering environments that could adversely affect the operation of the active implantable medical device, including areas protected by a warning notice that prevents entry by patients who have a pulse generator. Do not expose a patient to MRI device scanning. Strong magnetic fields may damage the device and cause injury to the patient. Do not subject a patient with an implanted pulse generator to diathermy since diathermy may cause fibrillation, burning of the myocardium, and irreversible damage to the pulse generator because of induced currents. Do not use atrial tracking modes (or an AVT device) in patients with chronic refractory atrial tachyarrhythmias. Tracking of atrial arrhythmias could result in VT or VF. (Applies to dual-chamber devices only.) Do not use this pulse generator with another pulse generator. This combination could cause pulse generator interaction resulting in patient injury or lack of therapy delivery. Do not kink leads. Kinking leads may cause additional stress on the leads, possibly resulting in lead fracture. For specific models, when using a subpectoral implantation, place the pulse generator with the serial number facing away from the ribs. Implanting the pulse generator subpectorally with the serial number facing the ribs may cause repetitive mechanical stress to a specific area of the titanium case, potentially leading to a component failure and device malfunction.
Precautions
For information on precautions, refer to the following sections of the product labeling: clinical considerations; sterilization, storage and handling; implantation and device programming; follow-up testing; explant and disposal; environmental and medical therapy hazards; home and occupational environments. Advise patients to avoid sources of electromagnetic interference (EMI) because EMI may cause the pulse generator to deliver inappropriate therapy or inhibit appropriate therapy.
Potential Adverse Events
Potential adverse events from implantation of the ICD system include, but are not limited to, the following: allergic/physical/physiologic reaction, death, erosion/migration, fibrillation or other arrhythmias, lead or accessory breakage (fracture/insulation/lead tip), hematoma/seroma, inappropriate or inability to provide therapy (shocks/pacing/sensing), infection, procedure related, psychologic intolerance to an ICD system - patients susceptible to frequent shocks despite antiarrhythmic medical management/imagined shocking, and component failure. In rare cases severe complications or device failures can occur.
Refer to the product labeling for specific indications, contraindications, warnings/ precautions and adverse events. Rx only.
(Rev. M)

26. Back up slide

27. 36% COMPANION Clinical Question
COMPANION: Providing New Access to CRT Therapies
COMPANION
Clinical Question
Does CRT therapy, used in combination with optimal pharmacologic therapy (OPT), significantly improve the quality and duration of life for patients with late-stage symptomatic heart failure versus using OPT alone? 1
Size: 1520 U.S. patients
Endpoint: All-cause mortality or first hospitalization
Published: NEJM 2004
36%
COMPANION: Providing New Access to CRT Therapies – Secondary Endpoint:
COMPANION demonstrated CRT-D can save lives in late-stage HF patients (Class III-IV). But the data showed that pump failure was still the most common cause of death – urging us to want to prevent or slow any patient’s progression to this stage of symptomatic heart failure.
**Source:
(1) 1 Bristow MR, et al, NEJM, 2004 ; 350 (21):
Reduction in the risk of all-cause mortality when using a CRT-D, in combination with OPT, when compared to OPT alone (p value:0.004) 1
1 Bristow MR, et al, NEJM, 2004 ; 350 (21):