incremental reduction in risk of death associated with use of guideline- recommended therapies in...

Incremental Reduction in Risk of Death Associated with Use of Guideline-

Recommended Therapies in Patients with Heart Failure: A Nested Case Control

Analysis of IMPROVE HF

Gregg C. Fonarow, Nancy M. Albert, Anne B. Curtis, Mihai Gheorghiade, Yang Liu, Mandeep R. Mehra, Christopher M.

O'Connor, Dwight Reynolds, Mary N. Walsh, Clyde W. Yancy

Fonarow GC, et al. J Am Heart Assoc. 2012;1:16-26.

Disclosures

• The IMPROVE HF registry is sponsored by Medtronic

• The sponsor had no role or input into the selection of end points or quality measures used in the study

• Outcome Sciences, Inc., a contract research organization, independently performed the practice site chart abstractions for IMPROVE HF, stored the data, and provided benchmarked quality of care reports to practice sites. Outcome Sciences received funding from Medtronic.

• Individually identifiable practice site data were not shared with either the steering committee or the sponsor

• Individual author disclosures are provided in the manuscript


Background: IMPROVE HF Nested Matched Case-Control Analysis

• Despite evidence from clinical trials, questions remain about translation of efficacy and safety of guideline-recommended heart failure (HF) therapies to real-world effectiveness in clinical practice

• A few observational study analyses explored the association between application of guideline-recommended therapies with clinical outcomes in HF, but not specific and incremental contributions of each therapy

• The goal of this analysis was to evaluate individual and incremental benefits for guideline-recommended HF therapies associated with 24-month survival


Background: IMPROVE HF Nested Matched Case-Control Analysis

• New HF therapies are tested on a background of existing guideline-recommended therapies, and relative clinical value of each new guideline-recommended therapy, independent of other therapies, has not been well studied

• Consequently with new evidence, professional society guidelines usually recommend that each new therapy be added to other established therapies

• Observational clinical and comparative effectiveness research has the potential to better inform clinical decision making


Study Objectives

The objectives of this study were to:

1)Evaluate the individual benefits associated with each of seven current ACC/AHA guideline-recommended therapies for HF and their association with 24-month survival in outcomes with chronic HF and reduced LVEF.

2)Determine the incremental gains associated with the guideline-recommended therapies on 24-month survival.


Methods: Definition of Cases and Controls

A nested matched case-control design was used because a large cohort of patients was available, enabling more explicit control of known powerful confounders, and because analysis would be less impacted by loss to follow-up.

Cases: Patient with HF who died from ANY cause within 24 months of follow-up (all-cause mortality used because less subject to interpretation).

Controls: Cohort patients who survived to 24 months.


Methods: Matching

• Cases/Controls matched on basis of their propensity score, and matched at 1:2 ratio using Greedy matching technique

• Logistic regression model used to generate probability of death

• Matches generated on the basis of non-missing covariates

• Per subsequent slides, cases and controls were generally well-matched


Methods: Guideline-Recommended Therapies

• Seven ACC/AHA HF guideline-recommended therapies (Class I) were prospectively selected:

– Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB)

– ß-blocker– Aldosterone antagonist– Anticoagulation therapy for atrial fibrillation/flutter (AF)– Cardiac resynchronization therapy with or without ICD (CRT)– Implantable cardioverter defibrillator with or without CRT (ICD)– Heart failure (HF) education

• Each therapy selected on basis of potential to improve patient outcomes, precision of definition, construct and content validity, and feasibility

• Patients who met guidelines-specified eligibility criteria for each individual therapy (with no contraindication, intolerance, or other documented reasons for not receiving it) were eligible for inclusion in the analyses for that therapy


Statistical Methods

• For each HF therapy, for eligible patients, the unadjusted odds ratio of death was determined using a logistic regression model with the therapy as the predictor variable and no covariate adjustment

• A univariate logistic regression analysis was then performed for each patient and practice characteristic assessed in this study to identify potential covariates for the multivariate logistic model

• These characteristics were fitted into a multivariate logistic regression model, with treatment as the main effect and the potential confounders as covariates, to determine the OR of death for each therapy among therapy-eligible patients who received the treatment at baseline versus therapy-eligible patients who did not receive baseline treatment in each study group

• Therapies were sequenced on the basis of their β-coefficients and the order in which they are commonly prescribed in clinical practice

• An additional set of analyses was conducted to evaluate the association between total number of guideline-recommended therapies received by all patients at baseline and death within 24 months


Results: Baseline Patient Characteristics for the 1:2 Matched Cohort

Characteristics

CohortP

Total (n = 4,128)) Case (Dead) (n = 1,376) Control (Alive) (n = 2,752)

Age, mean (SD), y 71.7 (11.8) 72.0 (12.4) 71.6 (11.5) 0.2396

Sex, n (%) Male Female

2,966 (71.9%)1,162 (28.1%)

980 (71.2%)396 (28.8%)

1,986 (72.2%)766 (27.8%)

0.5246

Race, n (%) Black/African American White Other Not documented/Missing

377 (9.1%)1,869 (45.3%)69 (1.7%)1,813 (43.9%)

145 (10.5%)627 (45.6%)14 (1.0%)590 (42.9%)

232 (8.4%)1,242 (45.1%)55 (2.0%)1,223 (44.4%)

0.0006

Insurance, n (%) Medicare Medicaid Private/Commercial Other None Not documented/Missing

2,829 (68.5%)134 (3.2%)786 (19.0%)118 (2.9%)37 (0.9%)224 (5.4%)

953 (69.3%)52 (3.8%)242 (17.6%)43 (3.1%)12 (0.9%)74 (5.4%)

1,876 (68.2%)82 (3.0%)544 (19.8%)75 (2.7%)25 (0.9%)150 (5.5%)

0.4963

Ischemic HF etiology, n (%) 2,893 (70.1%) 996 (72.6%) 1,897 (69.3%) 0.0781

Previous MI 1,715 (41.5%) 557 (40.5%) 1,158 (42.1%) 0.3258

History of CABG 1,413 (34.2%) 476 (34.6%) 937 (34.0%) 0.7279

History of PCI 1,082 (26.2%) 361 (26.2%) 721 (26.2%) 0.9800

History of Atrial Fibrillation 1,474 (35.7%) 492 (35.8%) 982 (35.7%) 0.9634


Characteristics

CohortP

Total (n = 4,128) Case (Dead) (n = 1,376) Control (Alive) (n = 2,752)

History of Hypertension 2,612 (63.3%) 874 (63.5%) 1,738 (63.2%) 0.8194

History of Diabetes 1,464 (35.5%) 495 (36%) 969 (35.2%) 0.6290

History of COPD 801 (19.4%) 285 (20.7%) 516 (18.8%) 0.1329

History of PVD 514 (12.5%) 176 (12.8%) 338 (12.3%) 0.6407

History of Depression 410 (9.9%) 151 (11.0%) 259 (9.4%) 0.1136

NYHA Class, n (%) I II III IVNot Documented

1,335 (32.3%)1,612 (39.1%)990 (24.0%)84 (2%)107 (2.6%)

419 (30.5%)558 (40.6%)331 (24.1%)34 (2.5%)34 (2.5%)

916 (33.3%)1,054 (38.3%)659 (23.9%)50 (1.8%)73 (2.7%)

0.2379

LVEF, % Mean (SD) Median (25th, 75th percentiles)

25.1 (7)25 (20, 30)

24.9 (7)25 (20, 30)

25.2 (7)25 (20, 30)

0.3102

Blood Pressure Systolic, mmHg, median (25th, 75th percentiles)Diastolic, mmHg, median (25th, 75th percentiles)

118 (106, 130)70 (60, 76)

118 (106, 130)69 (60, 76)

118 (108, 130)70 (60, 76)

0.75060.0785



CharacteristicsCohort

PTotal (n = 4,128) Case (Dead) (n = 1,376) Control (Alive) (n = 2,752)

Resting HR, bpm, Median (25th, 75th percentile)

72 (64, 80) 72 (64, 80) 71.5 (64, 79) 0.7007

Pulmonary Rales on last exam, n (%) 144 (3.5%) 41 (3.0%) 103 (3.7%) 0.4515

Edema on last exam, n (%) 896 (21.7%) 313 (22.7%) 583 (21.2%) 0.5173

Serum Sodium, mEq/Lmedian (25th, 75th percentiles)

140 (137, 142) 139 (137, 142) 140 (137, 142) 0.5941

Serum Urea Nitrogen, mg,dLMedian (25th, 75th percentiles)

23 (17, 31) 23 (17, 32) 23 (17, 30.5) 0.3465

Serum Creatinine, mg/dLMedian (25th, 75th percentiles)

1.3 (1.0, 1.6) 1.3 (1.0, 1.6) 1.3 (1.0, 1.6) 0.1723

Serum Potassium, mEq/LMedian (25th, 75th percentiles)

4.4 (4.1, 4.7) 4.4 (4.1, 4.8) 4.4 (4.1, 4.7) 0.8566

QRS Duration, msMedian (25th, 75th percentiles)

130 (102, 160) 126 (104, 158) 132 (102, 160) 0.7010



Results: Practice Characteristics

CharacteristicsCohort

PTotal (n = 4,128) Case (Dead) (n = 1,376) Control (Alive) (n = 2,752)

Census Region, n (%) South West Central Northeast

1,613 (39.1%)584 (14.1%)800 (19.4%)1131 (27.4%)

553 (40.2%)185 (13.4%)258 (18.8%)380 (27.6%)

1,060 (38.5%)399 (14.5%)542 (19.7%)751 (27.3%)

0.6075

Outpatient Practice Setting, n (%) Non-university, non-teaching Non-university, teaching University, teaching

2,821 (68.3%)914 (22.1%)393 (9.5%)

943 (68.5%)316 (23.0%)117 (8.5%)

1,878 (68.2%)598 (21.7%)276 (10%)

0.2360

Multi-specialty, n (%) 943 (22.8%) 325 (23.6%) 618 (22.5%) 0.4015

Electronic health record system, n (%) Paper Electronic Mixed

1,933 (46.8%)1,443 (35.0%)752 (18.2%)

636 (46.2%)473 (34.4%)267 (19.4%)

1,297 (47.1%)970 (35.2%)485 (17.6%)

0.3758

HF Nurse in practice (>1FTE APN), n (%) 1698 (41.1%) 553 (40.2%) 1145 (41.6%) 0.3628

No. of electrophysiologists in practice Mean (SD) Median (25th, 75th percentile)

1.7 (1.7)1 (0, 3)

1.7 (1.7)1 (0, 3)

1.7 (1.8)1 (0, 3)

0.4108

No. of interventionalists in practice Mean (SD) Median (25th, 75th percentile)

5.1 (3.3)5 (3, 6)

5.0 (3.3)5.0 (3, 6)

5.1 (3.3)5.0 (3, 6)

0.6872

No. of HF clinic sessions in practice Mean (SD) Median (25th, 75th percentiles)

1.5 (0.5)2 (1, 2)

1.5 (0.5)2 (1, 2)

1.5 (0.5)2 (1, 2)

0.9649

No. of cardiologists in practice Mean (SD) Median (25th, 75th percentiles)

13.9 (11.6)10 (7, 18)

13.6 (10.9)10 (7, 18.5)

14 (11.9)10 (7, 18)

0.2364

No. of HF patients managed annually Mean (SD) Median (25th, 75th percentiles)

3,601 (3968.6)2,319 (700, 5000)

3,565 (3820.2)2,319 (750, 5000)

3,619.4 (4043)2,319 (700, 5000)

0.6948


Results: Use of Guideline-Recommended Therapies in Cases (Dead) and Controls (Alive)

Use of guideline-recommended therapies at baseline in cases and controls. Baseline use of each of the therapies for cases (dead at 24 months) compared to controls (alive at 24 months).


Results: Cases vs. Controls 24-Month Mortality Unadjusted/Adjusted Odds Ratios

Quality Measure Treated, n (%)

Not Treated, n (%)

Unadjusted OR (95% CI)

p Adjusted OR (95% CI)

p

ACEI/ARB Cases (dead) Controls (alive)

969 (77.9%)2221 (86.4%)

275 (22.1%)351 (13.6%)

0.56 (0.47-0.66) < 0.0001 0.56 (0.47–0.67) < 0.0001

B-Blockers Cases (dead) Controls (alive)

1,059 (84.1%)2,332 (92.6%)

200 (15.9%)185 (7.4%)

0.42 (0.34-0.52) < 0.0001 0.42 (0.34-0.52) < 0.0001

Aldosterone Antagonists Cases (dead) Controls (alive)

127 (43.9%)246 (41.0%)

162 (56.1%)354 (59.0%)

1.13 (0.85-1.50) 0.4047 1.05 (0.74-1.51) 0.7707

Anticoagulants for AF Cases (dead) Controls (alive)

307 (69.1%)691 (75.8%)

137 (30.9%)221 (24.2%)

0.72 (0.56-0.92) 0.0096 0.73 (0.57-0.95) 0.0179

ICD Cases (dead) Controls (alive)

513 (52.0%)1,240 (63.6%)

473 (48.0%)709 (36.4%)

0.62 (0.53-0.72) < 0.0001 0.62 (0.53-0.73) < 0.0001

CRT Cases (dead) Controls (alive)

68 (41.2%)180 (56.1%)

97 (58.8%)141 (43.9%)

0.55 (0.38-0.80) 0.0020 0.44 (0.29-0.67) 0.0001

HF Education Cases (dead) Controls (alive)

1,042 (75.7%)2,246 (81.6%)

334 (24.3%)506 (18.4%)

0.70 (0.60-0.82) < 0.0001 0.73 (0.62-0.85) < 0.0001


Results: Mortality Reduction Based on Number of Guideline-Recommended Therapies at Baseline

24-Month MortalityAdjusted Odds Ratios (95% CI Displayed)

24-Month MortalityAdjusted Odds Ratios (95% CI Displayed)

Number of Therapies (vs. 0 or 1 therapy)

2 therapies

3 therapies

4 therapies

5, 6, or 7 therapies

Odds Ratio(95% confidence interval)

0.63 (0.47-0.85)(p = 0.0026)

0.38 (0.29-0.51)(p < 0.0001)

0.30 (0.23-0.41)(p < 0.0001)

0.31 (0.23-0.42)(p < 0.0001)

0 0.5 1 1.5 2


Incremental Benefits with HF Therapies(Cumulative % Reduction in Odds of Death at 24 Months)

-28% to -49%P<0.0001

-54% to -71%P<0.0001

-68% to -81%P<0.0001

-75% to -86%P<0.0001

-77% to -88%P<0.0001

-72% to -87%P<0.0001


Incremental Benefit with HF Therapies(Cumulative % Reduction in Odds of Death at 24 Months Associated with Sequential Treatments)

+20% to -68%P=0.1566

-43% to -91%P<0.0001

-70% to -96%P<0.0001


Summary of Results

• Individual benefits were demonstrated for each of the guideline-recommended therapies, with a single exception

• The strong associations between ACEI/ARB and beta blocker use and improved survival are consistent with clinical trial data

• Anticoagulation for AF was associated with reduced risk of mortality

• CRT strongly and independently associated with improved survival

• ICD significantly associated with a 38% lower odds of 2-year mortality

• Among the individual HF therapies evaluated, beta blockers and CRT seemed to provide the greatest individual benefits

• In contrast, aldosterone antagonist use was NOT associated with lower mortality after multivariate adjustment, a finding which requires further study


Summary of Results

• The study was among the first looking at individual and incremental clinical effectiveness of guideline-recommended therapies for patients with HF and reduced LVEF

• Using a nested case-control design, the impact of several guideline-recommended HF therapies, applied in current clinical practice in real-world patients, could be evaluated

• Substantial incremental benefits demonstrated with 81-90% reduction in the odds of 24-month mortality

• The positive association between progressive use of therapies appeared to plateau after any 4-5 therapies were applied

• The ability to independently value HF therapies may provide rationale for choosing among treatments when a choice must be made – for reasons of tolerance, cost and/or adherence


Limitations: Nested Case-Control Analysis

• Individual therapy analyses did not adjust for use of other background therapy

• Even after propensity matching/risk adjustment, differential indications for each therapy as a function of HF severity may still have influenced incremental benefit analyses

• Other measured/unmeasured confounding variables that would have strengthened or weakened association for some or all therapies

• Majority of patients receiving CRT received a CRT-D device – likely diminished ability to ascertain incremental benefit of CRT in some of the analyses

• Associations between use of guideline-recommended therapies and mortality do not determine causality – associations may reflect clinical effectiveness, and they may alternatively reflect treatment selection bias also


Conclusions

• This analysis demonstrated that – Guideline-recommended therapies for patients with HF and reduced LVEF

are associated with individual and incremental decreased risk of 24-month mortality

• Beta blocker and CRT had the strongest survival benefits observed

• Incremental benefit with each successive guideline-recommended therapy, plateauing after any 4-5 therapies were applied

• Provides further evidence for clinical effectiveness of guideline-recommended HF therapies for patients in real-world clinical practice

• Results suggest that benefit accrues incrementally with application of these therapies in the outpatient setting with 81-90% reductions in the odds of 24-month mortality

• These results provide further rationale for using systems, performance improvement, and HF disease management to ensure the implementation of guideline-recommended HF therapies into clinical practice


Back-Up Slides

IMPROVE HF Study Overview

• Largest, most comprehensive performance improvement study for HF patients in the outpatient setting

• Designed to enhance quality of care of HF patients by facilitating adoption of evidence-based, guideline-recommended therapies:

– Evaluate utilization rates of evidence-based, guideline-recommended HF therapies at baseline and over the course of the performance improvement intervention (chart audit and feedback; use of performance measures)

– Multifaceted, practice-specific performance improvement toolkit including clinical decision support tools (reminder systems)

– Sites attended an educational workshop to set treatment goals and develop a customized clinical care pathway (educational outreach)

Fonarow GC, et al. Am Heart J. 2007;154:12-38.

Patient Population

• To be enrolled in IMPROVE HF, patients had to have heart failure or post-myocardial infarction left ventricular dysfunction with left ventricular ejection fraction of 35% or less

• There were 15,177 patients from 167 cardiology and multispecialty practices in the United States evaluated at baseline and enrolled in the longitudinal cohort

• At the 24-month follow-up 11,621 of the 15,177 patients (76.6%) had documentation of vital status

• A total of 2,507 patients (16.5%) were lost to follow-up and 1,048 (6.9%) were seen in practices (n = 12) that did not complete the follow-up assessment

Fonarow GC, et al. Circulation. 2011;123:1601-1610.

Methods: Study Design and Patient Disposition

LongitudinalCohortLongitudinalCohort

Two Single-Time-PointCohorts

Two Single-Time-PointCohorts

Process Improvement Intervention (165 sites)

Baseline Chart Review

167 sites15,177 patients

Baseline Chart Review


12-Month Chart Review












Total Sites 167Patients Enrolled 34,810

Total Chart Reviews 63,143Total # of Site Visits 782





• Longitudinal cohort included the same patients reviewed at 3 time points

• Single-time-point cohorts included separate patients from the same practices and unique from the longitudinal cohort, as well as from each other

• Longitudinal cohort included the same patients reviewed at 3 time points

• Single-time-point cohorts included separate patients from the same practices and unique from the longitudinal cohort, as well as from each other


Methods: Guideline-Recommended Quality Measures

• Seven quality measures with strong evidence prospectively selected:– Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker

(ARB)*– ß-blocker*– Aldosterone antagonist– Anticoagulation therapy for atrial fibrillation/flutter (AF)*– Cardiac resynchronization therapy with or without ICD (CRT)– Implantable cardioverter defibrillator with or without CRT (ICD)– Heart failure (HF) education*

• Patients deemed eligible for individual quality measure based on meeting guideline criteria, without contraindications, intolerance, or other documented reasons for non-treatment

• Steering committee selected quality measures based on potential to improve patient outcomes, definition precision, construct and content validity, feasibility

* Included as ACC/AHA outpatient HF performance measure, endorsed by National Quality Forum.* Included as ACC/AHA outpatient HF performance measure, endorsed by National Quality Forum.


IMPROVE HF Outpatient Process Measures

Yancy CW, et al. Circulation. 2005;112:154-e235.Bonow RO, et al. J Am Coll Cardiol. 2005;46:1144-1178.

Methods: Patient Selection, Practice Selection, Data Collection, and Management

• Patient Inclusion:– Clinical diagnosis of HF or prior MI

with at least two prior clinic visits within 2 years

– LVEF ≤ 35% or moderate to severe left ventricular dysfunction

• Patient Exclusion:– Cardiac transplantation– Estimated survival < 1 year from

non-cardiovascular condition

• Average of 90 eligible patients per practice randomly selected for each of three study cohorts

• Practices: Outpatient cardiology (single specialty or multi-specialty) practices from all regions of the country

• Data quality measures– 34 trained, tested chart review

specialists– Training oversight by study steering

committee members– Monthly quality reports– Automated data field range, format,

unit checks

• Chart abstraction quality– Interrater reliability averaged

0.82 (kappa statistic)– Source documentation audit sample

concordance rate range of 92.3% to 96.3%

• Coordinating center: Outcome Sciences, Inc. (Cambridge, MA)– Individual practice data not shared with

sponsor or steering committee


Methods: Study Design and Patient Disposition

• Patients who were eligible for treatment but not treated at baseline and who crossed over within the first 12 months of the intervention were excluded from each measure

• Patients who were eligible for treatment but not treated at baseline and who crossed over within the first 12 months of the intervention were excluded from each measure


Methods: Practice Specific Performance Improvement Intervention

Practice Survey:

• 96% adopted one or more performance improvement strategies

• 85% used benchmarked quality reports

• 60% employed one or more IMPROVE HF tools

* Use or participation was encouraged but not mandatory. Practices could adopt or modify tools.* Use or participation was encouraged but not mandatory. Practices could adopt or modify tools.


-

IMPROVE HF Performance Intervention:Benchmarked Practice Profile Report

IMPROVE HF Performance Improvement Tools

• As part of an enhanced treatment plan, IMPROVE HF provided evidence-based best-practices algorithms, clinical pathways, standardized encounter forms, checklists, pocket cards, chart stickers, and patient education and other materials to facilitate improved management of outpatients with HF

• The materials can be downloaded from www.improvehf.com

• The materials are also included in the Circulation online-only Data Supplement


IMPROVE HF Practice Specific Education and Implementation Tools

www.improvehf.comwww.improvehf.com

Evidence Based Algorithmsand Pocket Cards

Patient Education Materials

Clinical Assessment and Management Forms

Clinical Trials and Current Guidelines

Dissemination of best practices:• Webcasts• Online Education• Newsletters

Brief Statement

IndicationsImplantable cardioverter defibrillators (ICDs) are indicated for ventricular antitachycardia pacing and ventricular defibrillation for automated treatment of life-threatening ventricular arrhythmias. Cardiac Resynchronization Therapy (CRT) ICDs are indicated for ventricular antitachycardia pacing and ventricular defibrillation for automated treatment of life-threatening ventricular arrhythmias and for the reduction of the symptoms of moderate to severe heart failure (NYHA Functional Class III or IV) in those patients who remain symptomatic despite stable, optimal medical therapy and have a left ventricular ejection fraction less than or equal to 35% and a prolonged QRS duration. CRT IPGs are indicated for the reduction of the symptoms of moderate to severe heart failure (NYHA Functional Class III or IV) in those patients who remain symptomatic despite stable, optimal medical therapy, and have a left ventricular ejection fraction less than or equal to 35% and a prolonged QRS duration. Contraindications IPGs and CRT IPGs are contraindicated for dual chamber atrial pacing in patients with chronic refractory atrial tachyarrhythmias; asynchronous pacing in the presence (or likelihood) of competitive paced and intrinsic rhythms; unipolar pacing for patients with an implanted cardioverter defibrillator because it may cause unwanted delivery or inhibition of ICD therapy; and certain IPGs are contraindicated for use with epicardial leads and with abdominal implantation. ICDs and CRT ICDs are contraindicated in patients whose ventricular tachyarrhythmias may have transient or reversible causes, patients with incessant VT or VF, and for patients who have a unipolar pacemaker. Warnings/PrecautionsChanges in a patient’s disease and/or medications may alter the efficacy of the device’s programmed parameters. Patients should avoid sources of magnetic and electromagnetic radiation to avoid possible underdetection, inappropriate sensing and/or therapy delivery, tissue damage, induction of an arrhythmia, device electrical reset, or device damage. Do not place transthoracic defibrillation paddles directly over the device. Additionally, for CRT ICDs and CRT IPGs, certain programming and device operations may not provide cardiac resynchronization. Also for CRT IPGs, Elective Replacement Indicator (ERI) results in the device switching to VVI pacing at 65 ppm. In this mode, patients may experience loss of cardiac resynchronization therapy and/or loss of AV synchrony. For this reason, the device should be replaced prior to ERI being set. Potential ComplicationsPotential complications include, but are not limited to, rejection phenomena, erosion through the skin, muscle or nerve stimulation, oversensing, failure to detect and/or terminate arrhythmia episodes, and surgical complications such as hematoma, infection, inflammation, and thrombosis. An additional complication for ICDs and CRT ICDs is the acceleration of ventricular tachycardia. See the device manual for detailed information regarding the implant procedure, indications, contraindications, warnings, precautions, and potential complications/adverse events. For further information, please call Medtronic at 1 (800) 328-2518 and/or consult Medtronic’s website at www.medtronic.com. Caution: Federal law (USA) restricts these devices to sale by or on the order of a physician.

UC201205289 ENFebruary 2012

incremental reduction in risk of death associated with use of guideline- recommended therapies in...

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