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DynaMed Plus

DynaMed Plus is the next-generation clinical reference tool physicians can rely on for fast, easy access to point-of-care decision support. Written by a team of specialized physicians and researchers, content is updated several times daily to include information on the latest evidence-based research, providing practice-changing answers to clinical questions with optimized speed. 

Cardiac resynchronization therapy (CRT)

  • Updated 2017 Mar 21 02:12:00 PM: review of right heart-pulmonary circulation unit and cardiac resynchronization therapy (Am Heart J 2017 Mar) view update
  • FDA warns of potential cybersecurity vulnerabilities associated with St. Jude Medical's radio frequency (RF)-enabled implantable cardiac devices and Merlin@home Transmitter (FDA MedWatch 2017 Jan 9) view update
  • FDA warns of premature battery depletion in implantable cardioverter defibrillators and cardiac resynchronization therapy defibrillators manufactured by St. Jude Medical before May 2015 (FDA Safety Communication 2016 Oct 11) view update

 

Overview and Recommendations

Background

  • Interventricular dyssynchrony occurs when there is a difference in timing of contractions between the right and left ventricle.
  • It is most commonly associated with conduction abnormalities and in particular left bundle branch block.
  • Cardiac resynchronization therapy (CRT) uses biventricular pacing to restore synchronous contraction of the left and right ventricle.
  • CRT can be used in Interventricular dyssynchrony with medication refractory heart failure to improve cardiac function and treatment of heart failure.
  • CRT is often used in combination with a defibrillator (CRT-D).

Evaluation

  • Obtain the following tests in patients with medication refractory heart failure to determine if they are candidates for CRT:
    • transthoracic echocardiogram or other modality to determine left ventricular ejection fraction (LVEF)
    • electrocardiogram to determine the rhythm, and to evaluate QRS morphology and duration

Management

  • Offer CRT if left ventricular ejection fraction (LVEF) is ≤ 35%, left bundle branch block (LBBB) QRS morphology, and QRS interval is ≥ 150 milliseconds (Strong recommendation).
  • Consider CRT if LVEF is ≤ 35% and either of (Weak recommendation):
    • QRS has non-LBBB morphology and QRS interval is > 150 millisecondsr
    • QRS has LBBB morphology and QRS interval is 120-149 milliseconds
  • CRT may also be considered if LVEF is ≤ 35%, QRS has non-LBBB morphology and QRS interval is 120-150 milliseconds (Weak recommendation).
  • Do not use CRT in patients with (Strong recommendation):
    • Class I or II heart failure, QRS interval < 150 milliseconds, and non-LBBB
    • comorbidities and/or frailty that limit survival with good functional capacity to < 1 year
  • In patients for whom an implantable cardioverter defibrillator (ICD) is planned, offer CRT with defibrillator (CRT-D) (Strong recommendation).
  • Consider CRT-D implantation if CRT is planned and the patient has a life expectancy of > 1 year, NYHA Class II heart failure, ischemic heart disease, or lack of comorbidities (Weak recommendation).

Overview

 

General Information

Description

  • Cardiac resynchronization therapy (CRT) is used to correct ventricular dyssynchrony caused by conduction abnormalities in patients with medication refractory heart failure who are in sinus rhythm(1, 2, 3)
  • CRT uses biventricular pacing to restore synchronous contraction of the left and right ventricle(1)
  • benefits of CRT may include(1, 2, 3)
    • reduction in heart failure symptoms without increase in myocardial energy consumption
    • improved ventricular contraction
    • reduced mitral regurgitation
    • reverse ventricular remodeling
    • improved left ventricular ejection fraction
  • CRT can be delivered via CRT pacemaker or CRT-defibrillator (CRT-D)(6)

Epidemiology

  • CRT indicated in 5%-10% of patients with heart failure(3)
    • estimated 400,000 patients per year may be suitable for CRT in Europe
  • CRT use increased from 2005 to 2011(3)

Heart Failure Classification

New York Heart Association (NYHA) heart failure classification

NYHA Functional Classification:
NYHA ClassPatient Symptoms
Class I (mild)
  • No limitation of physical activity
  • Ordinary physical activity does not cause symptoms of heart failure (undue fatigue, palpitations, and dyspnea)
Class II (mild)
  • Slight limitation of physical activity
  • Comfortable at rest, but ordinary physical activity results in symptoms of heart failure
Class III (moderate)
  • Significant limitation of physical activity
  • Comfortable at rest, but less than ordinary activity causes symptoms of heart failure
Class IV (severe)
  • Unable to carry out any physical activity without symptoms of heart failure or symptoms of heart failure at rest
Abbreviation: NYHA, New York Heart Association.

Reference - Circulation 2013 Oct 15;128(16):e240 PDF

American College of Cardiology Foundation/American Heart Association (ACCF/AHA) heart failure classification

ACCF/AHA Staging of Heart Failure:
Stage AAt high risk for heart failure but without structural heart disease or symptoms of heart failure
Stage BStructural heart disease but without signs or symptoms of heart failure
Stage CStructural heart disease with prior or current symptoms of heart failure
Stage DRefractory heart failure requiring specialized interventions
Abbreviation: ACCF/AHA, American College of Cardiology/Foundation/American Heart Association.

Reference - Circulation 2013 Oct 15;128(16):e240 PDF

Interagency Registry for Mechanically Assisted Support (INTERMACS) advanced heart failure profiles

  • INTERMACS clinical profiles
      Level 1Level 2 Level 3 Level 4 Level 5 Level 6 Level 7
    DescriptionCritical cardiogenic shock ("crash and burn")Progressive decline on inotropic support ("sliding on inotropes”)Stable but inotrope dependent, (“dependent stability")Resting symptoms (“frequent flyer”)Exertion intolerant, houseboundExertion limited (“walking wounded”)Advanced NYHA III (“symptoms, placeholder”)
    Hemodynamic StatusPersistent hypotension despite rapidly escalating inotropic support and eventually IABP, and critical organ hypoperfusionIV inotropic support with acceptable values of blood pressure and continuing deterioration in nutrition, renal function, or fluid retentionStability reached with mild to moderate doses of inotropes but demonstrating failure to wean from them because of hypotension, worsening symptoms, or progressive renal dysfunctionPossible weaning of inotropes but experiencing recurrent relapses, usually fluid retentionSevere limited tolerance for activity, comfortable at rest with some volume overload and often with some renal dysfunctionLess severe limited tolerance for activity and lack of volume overload, fatigue easilyPatient without current or recent unstable fluid balance, NYHA class II or III
    Time Frame for InterventionWithin hoursWithin daysElective over weeks to monthsElective over weeks to monthsVariable urgency, dependent on nutrition and organ functionVariable urgency, dependent on nutrition and organ functionNot currently indicated
    Abbreviations: IABP, intra-aortic balloon pump; NYHA, New York Heart Association.

Indications

  • Scottish Intercollegiate Guidelines Network (SIGN) recommendations for cardiac resynchronization therapy (CRT) with defibrillation (CRT-D) or pacing (CRT-P) in patients with heart failure with reduced ejection fraction (left ventricular ejection fraction ≤ 35%) based on New York Heart Association (NYHA) functional class and presence of left bundle branch block (LBBB)
    • in patients with NYHA class IV heart failure
      • CRT-P recommended if (SIGN Strong recommendation)
        • QRS interval ≥ 150 milliseconds in patients with and without LBBB
        • QRS interval 120-149 milliseconds in patients with and without LBBB
      • CRT not recommended if QRS interval < 120 milliseconds (SIGN Strong recommendation)
    • in patients with NYHA class III heart failure, CRT-P or CRT-D recommended if (SIGN Strong recommendation)
      • QRS interval ≥ 150 milliseconds in patients with and without LBBB
      • QRS interval 120-149 milliseconds in patients with LBBB
    • in patients with NYHA class II heart failure, CRT-D recommended if (SIGN Strong recommendation)
      • QRS interval ≥ 150 milliseconds in patients with and without LBBB
      • QRS interval 120-149 milliseconds in patients without LBBB
    • in patients with NYHA class I heart failure, CRT-D recommended if patients with QRS interval ≥ 150 milliseconds in patients with and without LBBB (SIGN Strong recommendation)
    • patients receiving CRT should be offered pre- and post-placment counseling, including discussion of potential shocks from device and device activation (SIGN Good Practice Point)
    • Reference - Scottish Intercollegiate Guidelines Network (SIGN) National clinical guideline for management of chronic heart failure (SIGN 2016 Mar PDF)

Contraindications

  • CRT contraindicated in patients with
  • CRT should not be used as rescue therapy for patients with stage D heart failure(1)
  • defer CRT implantation in patients with acutely decompensated heart failure who depend on inotropes or have unstable ventricular arrhythmias until medical status improves(6)

Efficacy

Cardiac resynchronization therapy (CRT) in heart failure

  • two cardiac resynchronization pacemakers manufactured by Medtronic FDA approved for expanded use in patients with atrioventricular block and less severe heart failure (FDA Press Release 2014 Apr 10)
  • CRT may reduce mortality in patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony (level 2 [mid-level] evidence)
    • based on systematic review of trials with methodologic limitations
    • systematic review of 26 randomized trials evaluating implantable cardioverter defibrillator (ICD) for ventricular arrhythmias or CRT for heart failure
    • all trials comparing CRT to optimal medical therapy had unclear allocation concealment and/or no blinding
    • definitions for left ventricular systolic dysfunction and cardiac dyssynchrony were as described by trial investigators (no arbitrary cutoff used for inclusion)
    • 4 trials compared CRT to optimal medical therapy or CRT plus ICD in patients with heart failure due left ventricular systolic dysfunction (LVSD) and cardiac dyssynchrony despite optimal medical treatment
    • comparing CRT to optimal medical therapy
      • CRT associated with
        • decreased all-cause mortality in analysis of 4 trials with 2,307 patients
          • risk ratio (RR) 0.75 (95% CI 0.58-0.96)
          • NNT 10-100 with 25% all-cause mortality in optimal medical therapy group
        • decreased heart failure-related mortality in analysis of 2 trials with 1,738 patients
          • RR 0.67 (95% CI 0.51-0.88)
          • NNT 15-60 with heart failure-related mortality in 14% of optimal medical therapy group
        • decreased hospitalization due to heart failure in analysis of 4 trials with 2,249 patients
          • RR 0.61 (95% CI 0.44-0.83)
          • NNT 6-20 with hospitalization due to heart failure in 30% of optimal medical therapy group
        • decreased worsening of heart failure in analysis of 3 trials with 1,383 patients
        • increased improvement by ≥ 1 NYHA class (RR 1.68, 95% CI 1.52-1.86) in analysis of 3 trials with 1,908 patients
        • improved health-related quality of life in analysis of 4 trials with 1,976 patients
      • no significant differences in
        • total cardiac deaths in 2 trials with 983 patients
        • sudden cardiac death in analysis of 3 trials with 1,854 patients, results limited by significant heterogeneity
    • comparing CRT plus ICD vs. optimal medical therapy in 1 trial with 903 patients
      • all-cause mortality at 1 year 12% vs. 19% (p = 0.003, NNT 15)
      • total cardiac mortality 12.8% vs. 18.8% (p = 0.006, NNT 17)
      • ≥ 1 hospitalization due to heart failure 28% vs. 36% (p = 0.008, NNT 13)
      • CRT plus ICD also significantly reduced sudden cardiac death
    • comparing CRT plus ICD vs. CRT alone in 1 trial with 1,212 patients
      • total cardiac mortality 12.8% vs. 17.7% (p = 0.02, NNT 21)
      • CRT plus ICD also significantly reduced sudden cardiac death
      • no significant differences in all-cause mortality and hospitalization due to heart failure
    • Reference - Health Technol Assess 2014 Aug;18(56):1
  • CRT associated with decreased adverse clinical events in class I-IV heart failure patients with QRS interval ≥ 150 milliseconds but not in patients with QRS interval 120-149 milliseconds (level 2 [mid-level] evidence)
    • based on systematic review without assessment of trial quality
    • systematic review of 5 randomized trials evaluating CRT for reducing adverse clinical events in patients with heart failure
      • patients stratified by QRS interval (120-149 milliseconds defined as moderately prolonged, ≥ 150 milliseconds as severely prolonged)
      • 2 trials included 1,738 patients with NYHA Class III-IV symptoms (severely prolonged QRS interval in 64%)
      • 3 trials included 4,228 patients with NYHA Class I-II symptoms (severely prolonged QRS interval in 60%)
    • all studies used composite outcome for adverse clinical events including
      • all-cause mortality in all trials
      • any hospitalization in 1 trial
      • any cardiovascular hospitalization in 1 trial
      • heart failure-related event or hospitalization in 3 trials
    • control conditions included medical therapy in 3 trials, no CRT in 1 trial, CRT implanted but turned off in 1 trial
    • range of mean follow-up was 12-40 months
    • CRT associated with decreased risk of composite adverse clinical events in patients with severely prolonged QRS interval in
      • all patients (risk ratio [RR] 0.6, 95% CI 0.53-0.67)
      • patients with NYHA Class I-II symptoms (RR 0.47, 95% CI 0.37-0.6)
      • patients with NYHA Class III-IV symptoms (RR 0.67, 95% CI 0.57-0.8)
    • no significant differences in risk of composite adverse clinical events in patients with moderately prolonged QRS interval in
      • all patients
      • patients with NYHA Class I-II symptoms
      • patients with NYHA Class III-IV symptoms
    • Reference - Arch Intern Med 2011 Sep 12;171(16):1454
  • CRT may not reduce mortality or heart failure-related hospitalization in patients with non-left bundle branch block QRS morphology (level 2 [mid-level] evidence)
    • based on subgroup analyses of randomized trials in systematic review
    • systematic review of randomized trials comparing CRT vs. control in patients with non-left bundle branch block (LBBB) QRS morphology
      • review included 6 trials with 6,914 patients, including subgroup of 1,683 patients with non-LBBB QRS morphology
      • patients had NYHA Class I-IV symptoms, QRS interval ≥ 120 milliseconds, and left ventricular ejection fraction (LVEF) ≤ 30% or ≤ 40%
    • CRT defibrillator or CRT pacemaker was evaluated alone or in combination with medical therapy
    • controls included no treatment, implantable cardioverter-defibrillator, medical therapy, and implantable cardioverter-defibrillator plus medical therapy
    • no significant differences between groups in
      • mortality in analysis of 3 trials
      • hospitalization due to heart failure in analysis of 3 trials
      • composite outcome of mortality or hospitalization due to heart failure in analysis of 5 trials, results limited by significant heterogeneity
    • Reference - Heart 2015 Sep 15;101(18):1456
  • insufficient evidence to evaluate CRT in patients with left ventricular systolic dysfunction, prolonged QRS interval, and right bundle branch block
    • based on systematic review of 5 randomized trials evaluating CRT in 5,456 patients with left ventricular systolic dysfunction and prolonged QRS interval
    • no trials compared patients with right bundle branch block to those without
    • Reference - Heart Rhythm 2011 Jul;8(7):1083

Cardiac resynchronization therapy for Class III/IV heart failure

  • CRT reduces mortality and hospitalization rate, and improves quality of life and ejection fraction for patients with Class III/IV heart failure and prolonged QRS interval > 150 msec, but not in patients with moderately prolonged (120-150 msec) QRS interval
    • CRT reduces mortality and hospitalization and improves quality of life for patients with NYHA Class III or IV heart failure and prolonged QRS interval (level 1 [likely reliable] evidence)
      • based on 3 systematic reviews
      • addition of CRT to optimal medical therapy reduces mortality in patients with NYHA Class III or ambulatory IV heart failure and QRS interval > 150 milliseconds (level 1 [likely reliable] evidence)
        • based on systematic review
        • systematic review of 12 randomized trials evaluating addition of CRT to optimal medical therapy or ICD in 7,538 patients with NYHA Class III or ambulatory IV heart failure and mean QRS interval 153-176 milliseconds
        • CRT plus optimal medical therapy vs. optimal medical therapy alone evaluated in 5 trials with 2,355 patients and > 98% with NYHA Class III or ambulatory IV heart failure symptoms
          • CRT reduced mortality (relative risk [RR] 0.73, 95% CI 0.62-0.85)
          • NNT 11-27, assuming 25% mortality with optimal therapy alone
          • all 5 trials favored CRT, but only 1 was statistically significant alone
        • Reference - CMAJ 2011 Mar 8;183(4):421 full-text
      • systematic review of 14 randomized trials comparing cardiac resynchronization therapy (CRT) vs. usual care
        • 4,420 patients included had systolic dysfunction (mean ejection fraction range 21%-30%), prolonged QRS duration (mean range 155-209 milliseconds), and > 90% with New York Heart Association (NYHA) Class III or IV symptoms
        • trials evaluated CRT alone or combined CRT-implantable cardioverter defibrillator (ICD) devices
        • comparing CRT to usual care, CRT associated with
          • reduced all-cause mortality (relative risk [RR] 0.78, 95% CI 0.67-0.91) in analysis of 14 trials with 3,825 patients
            • among patients with symptomatic heart failure (NYHA Class II-IV) NNT 29 over median follow-up 6 months
            • among patients with Class III or IV heart failure NNT 23 over median follow-up 3 months
          • reduced progressive heart failure mortality (RR 0.64, 95% CI 0.49-0.84) in analysis of 8 trials with 3,004 patients
          • reduced proportion of patients hospitalized for heart failure (RR 0.63, 95% CI 0.43-0.93) in analysis of 7 trials with 2,270 patients, heterogeneity explained by no benefit in 2 trials comparing combined CRT-ICD vs. ICD alone
          • improvement by ≥ 1 NYHA Class in 59% vs. 37% (p < 0.05, NNT 5) in analysis of 3 trials, but results limited by heterogeneity
          • improved quality of life based on Minnesota Living with Heart Failure Questionnaire (weighted mean difference [WMD] for reduction 8, 95% CI 5.6-10.4) in analysis of 11 trials
          • improved ejection fraction (WMD 3%, 95% CI 0.9%-5.1%) in analysis of 5 trials
        • no significant differences in sudden cardiac death (11 trials) or noncardiac death (6 trials)
        • CRT implantation associated with mortality about 0.3% and successful implantation > 90%
        • Reference - Evid Rep Technol Assess (Full Rep) 2007 Jun;(152):1
      • systematic review of 9 randomized trials without assessment of trial quality
    • in patients with NYHA Class III or IV heart failure and QRS interval < 130 milliseconds, CRT does not reduce mortality or hospitalization for heart failure and may increase all-cause mortality (level 1 [likely reliable] evidence)
      • based on randomized trial
      • 809 adults (mean age 58 years) with NYHA Class III or IV heart failure, left ventricular ejection fraction ≤ 35%, QRS duration < 130 milliseconds, and echocardiographic evidence of left ventricular dyssynchrony had implantation of cardiac device with CRT and ICD capability and were randomized to CRT turned on vs. off
      • planned recruitment of 1,132 patients but trial terminated early by data and safety monitoring board due to futility with potential of harm with CRT
      • mean follow-up 19.4 months
      • comparing CRT on vs. off
        • all-cause mortality or hospitalization for worsening heart failure in 28.7% vs. 25.2% (not significant)
        • all-cause mortality 11.1% vs. 6.4% (p = 0.02, NNH 21)
        • hospitalization for worsening heart failure in 24.5% vs. 22.2% (not significant)
        • cardiovascular hospitalization in 36.4% vs. 33.8% (not significant)
      • no significant difference in quality of life
      • Reference - EchoCRT trial (N Engl J Med 2013 Oct 10;369(15):1395)
      • no significant differences in effect of CRT comparing patients with QRS duration 120-130 ms vs. QRS duration < 120 ms in prespecified subgroup analysis (Eur Heart J 2015 Aug 7;36(30):1983)
    • optimization of CRT device may not improve walking capacity or quality of life but may slightly increase left ventricular ejection fraction in patients with NYHA Class III or IV heart failure (level 2 [mid-level] evidence)
      • based on systematic review limited by heterogeneity
      • systematic review of 13 randomized trials or nonrandomized studies comparing optimization of CRT device vs. no optimization in 1,431 patients with heart failure
      • all patients had New York Heart Association functional class III or IV, LVEF < 35%, and prolonged QRS
      • optimization methods included Ritter and iterative methods for atrioventricular optimization and left ventricular outflow tract velocity time integral method for interventricular optimization
      • results for LVEF, 6-meter walking distance, and health-related quality of life limited by significant heterogeneity
      • no significant differences in 6-meter walking distance and health-related quality of life in analyses of 6 trials
      • optimization of CRT device associated with increased LVEF (mean difference 2.6%, 95% CI 0.8%-4.4%) in analysis of 10 trials
      • Reference - Am J Cardiol 2014 Mar 15;113(6):988

Cardiac resynchronization therapy for Class I/II heart failure

  • CRT may reduce mortality and hospitalization for heart failure in patients with NYHA Class I-II symptoms and QRS interval > 120 milliseconds (level 2 [mid-level] evidence)
    • based on systematic review of trials with allocation concealment not stated
    • systematic review of 25 randomized trials evaluating CRT in 9,082 patients with heart failure
      • 24 trials included only patients with QRS duration ≥ 120 milliseconds, 1 trial with 172 patients with narrower QRS duration required evidence of mechanical dyssynchrony on echocardiography
      • 3 trials (2,616 patients) included only patients with NYHA Class I or II symptoms
      • 2 trials (1,158 patients) included mostly NYHA Class I-II patients but did not report outcomes stratified by class
      • in 1 trial with 798 patients, 80% had Class II symptoms
      • remaining trials included exclusively, or predominantly, patients with Class III-IV symptoms
    • in analysis of trials with predominantly NYHA Class I-II symptoms, CRT associated with
      • reduced all-cause mortality in analysis of 6 trials with 4,572 patients
        • risk ratio 0.83 (95% CI 0.72-0.96)
        • NNT 24-167 with 15% mortality in controls
        • no significant differences in mortality in 3 trials that included only patients with Class I-II symptoms
      • reduced risk of hospitalization for heart failure in analysis of 4 trials with 4,349 patients
        • risk ratio 0.71 (95% CI 0.57-0.87)
        • NNT 12-39 assuming hospitalization in 20% of controls
    • mortality and hospitalization significantly reduced in analysis of trials with patients with Class III-IV symptoms
    • Reference - Ann Intern Med 2011 Mar 15;154(6):401, editorial can be found in Ann Intern Med 2011 Mar 15;154(6):436
  • CRT associated with increased time to first heart failure hospitalization or death in patients with NYHA Class I or II heart failure and left ventricular ejection fraction ≤ 40% but > 30% (level 2 [mid-level] evidence)
    • based on post hoc subgroup analysis of randomized trial
    • 610 patients with NYHA Class I or II heart failure who had left ventricular ejection fraction (LVEF) ≤ 40% and QRS duration ≥ 120 milliseconds despite optimal medical therapy had implantation of CRT device and were randomized to device turned on vs. off for 1 year
    • 177 patients (29%) had LVEF > 30% at baseline
    • CRT associated with significantly increased time to first heart failure hospitalization or death and decreased left ventricular end systolic volume index in patients with LVEF > 30%
    • consistent findings in patients with LVEF ≤ 30%
    • Reference - Circ Heart Fail 2013 Nov;6(6):1180 full-text
  • 5-year mortality reported to be 13.5% for CRT in patients with NYHA Class I or II heart failure (level 3 [lacking direct] evidence)
    • based on follow-up of randomized trial without comparative data
    • 610 patients with NYHA Class I or II heart failure, QRS interval ≥ 120 milliseconds, and left ventricular ejection fraction ≤ 40% who had cardiac resynchronization device implantation were randomized to device on vs. device off for 1 year
    • 419 patients who had device on were followed for mean 54.8 months
    • outcomes at 5 years in device-on group
      • mortality 13.5%
      • death or first heart failure hospitalization in 28.1%
      • left ventricular lead-related complications in 12.5%
    • Reference - Eur Heart J 2013 Sep;34(33):2592, editorial can be found in Eur Heart J 2013 Sep;34(33):2582

Device Warnings and Recalls

  • FDA warns of potential cybersecurity vulnerabilities associated with St. Jude Medical's radio frequency (RF)-enabled implantable cardiac devices and Merlin@home Transmitter
    • FDA confirmed that if vulnerabilities exploited, unauthorized user could remotely access a patient's RF-enabled implanted cardiac device by altering Merlin@home Transmitter
    • altered transmitter could be used to modify programming commands to implanted device, which could result in rapid battery depletion and/or administration of inappropriate pacing or shocks
    • validated software patch for Merlin@home Transmitter created to reduce risk of exploitation and subsequent patient harm
    • FDA has not received reports of patient harm related to these cybersecurity vulnerabilities and has determined that benefits from continued use of device outweigh potential risks
    • recommendations for health care providers
      • continue to conduct routine in-office follow-up with patients who have an implantable cardiac device that is monitored using the Merlin@home Transmitter
      • remind patients to keep their Merlin@home Transmitter connected to ensure that patients' devices receive necessary patches and updates
    • patients and caregivers should follow labeling instructions provided with Merlin@home Transmitter to ensure monitor receives necessary updates and patches
    • Reference - FDA MedWatch 2017 Jan 9
  • FDA warns of premature battery depletion in implantable cardioverter defibrillators and cardiac resynchronization therapy defibrillators manufactured by St. Jude Medical before May 2015
    • 2 deaths and 47 patients with dizziness or fainting associated with premature battery depletion reported (349,852 potentially affected devices actively implanted worldwide); list of affected implantable Cardioverter Defibrillators (ICDs) and Cardiac Resynchronization Therapy Defibrillators (CRT-Ds) may be found at FDA Safety Communication 2016 Oct 11
    • once Elective Replacement Indicator (ERI) vibratory alert occurs, patients do not have normal 3 month lead time for device replacement as full battery drainage may occur within 24 hours to a few weeks
    • prophylactic device replacement prior to ERI not required in most patients, as rate of complications associated with replacement surgery are higher than those with premature battery depletion
    • devices should be immediately replaced at time of ERI alert; pacemaker-dependent patients with a device that has reached ERI should be treated as a medical emergency
    • FDA strongly recommends all patients with affected implanted devices enroll in St. Jude Medical’s home monitoring system (Merlin@Home), particularly those patients with difficulty recognizing their device’s ERI alerts
    • Reference - FDA Safety Communication 2016 Oct 11
  • inventory retrieval of implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT) defibrillators from Boston Scientific due to incorrect approval submission
  • Class I recall of approximately 21,000 Medtronic Kappa and Sigma pacemakers
  • about 73,000 Boston Scientific/Guidant Implantable Cardiac Defibrillators and Cardiac Resynchronization Therapy Defibrillators (subset of CONTAK RENEWAL 3 & 4, VITALITY, and VITALITY 2 devices) recalled due to early battery depletion (FDA MedWatch 2007 Apr 12, FDA Guidant Recall 2007 Apr 10)

Cardiac Resynchronization Therapy with Defibrillator (CRT-D)

Indications

  • CRT-D recommended if CRT indicated and ICD planned (ESC Class I, Level A)(3)
  • CRT-D device implantation suggested if CRT planned and patient has any of the following (ESC Class IIa, Level B)(3)
    • life expectancy > 1 year
    • NYHA Class II heart failure
    • ischemic heart disease
    • lack of comorbidities

Efficacy

CRT-D vs. implantable cardioverter defibrillator (ICD) alone

  • CRT-D appears to reduce mortality and heart failure hospitalization compared to ICD alone in multiple patient populations
    • CRT-D may reduce mortality compared to ICD alone in patients with NYHA Class I-IV heart failure (level 2 [mid-level] evidence)
      • based on systematic review with some mixed results in trials with implantable cardioverter defibrillator (ICD) therapy
      • systematic review of 12 randomized trials evaluating addition of CRT to optimal medical therapy or ICD in 7,538 patients with NYHA Class I-IV heart failure and mean QRS interval 153-176 milliseconds
      • comparing CRT with defibrillator (CRT-D) to ICD in analysis of 7 trials with 5,184 patients
        • CRT-D associated with reduced mortality in overall analysis (relative risk [RR] 0.83, 95% CI 0.72-0.96)
          • NNT 25-177, with 14% mortality with ICD alone
          • although no statistical heterogeneity individual trial results were mixed with
            • 3 smaller trials with nonsignificant results favoring ICD alone
            • 2 smaller trials with nonsignificant results consistent with no effect
            • 1 small trial with nonsignificant results favoring CRT plus ICD
            • 1 large trial (RAFT trial) with significant results favoring CRT plus ICD
        • CRT-D associated with reduced mortality in subgroup analysis of 4 trials with 4,054 patients with New York Heart Association (NYHA) Class I or II heart failure
          • RR 0.8 (95% CI 0.67-0.96)
          • NNT 9-207 with 12% mortality with ICD alone
          • significant results driven solely by RAFT trial
        • no significant difference in mortality in subgroup analysis of patients with NYHA Class III or IV heart failure (4 trials with 1,130 patients)
      • Reference - CMAJ 2011 Mar 8;183(4):421 full-text
    • CRT-D may reduce mortality compared to ICD alone in patients with ventricular arrhythmias and heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony (level 2 [mid-level] evidence)
      • based on systematic review without significant differences in high-quality trials
      • systematic review of 26 randomized trials evaluating implantable cardioverter defibrillator (ICD) for ventricular arrhythmias or cardiac resynchronization therapy (CRT) for heart failure
      • definitions for left ventricular systolic dysfunction and cardiac dyssynchrony were as described by trial investigators (no arbitrary cutoff used for inclusion)
      • Minnesota Living with Heart Failure Questionnaire is 0-105 point scale with higher score indicating poorer quality of life, minimum clinically important difference 5 points
      • 9 trials compared CRT-D vs. ICD alone in patients at risk of sudden cardiac death due to ventricular arrhythmias and with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony
      • CRT-D associated with
        • decreased all-cause mortality in analysis of 9 trials with 5,064 patients
          • risk ratio (RR) 0.84 (95% CI 0.73-0.96)
          • NNT 27-179 with 14% all-cause mortality in ICD alone group
          • results significant only in 1 trial (RAFT trial) in which patients had NYHA class II heart failure (trial had 72% of weight in analysis)
          • no significant difference in 2 high-quality trials enrolling patients with class II or class III heart failure
        • decreased hospitalization due to heart failure in analysis of 3 trials with 2,319 patients
          • RR 0.75 (95% CI 0.64-0.88)
          • NNT 12-35 with hospitalization due to heart failure in 24% of ICD alone group
        • improved health-related quality of life (mean difference -6.9, 95% CI -10.41 to -3.4 on Minnesota Living with Heart Failure Questionnaire) in analysis of 6 trials with 1,309 patients
        • nonsignificant improvement in NYHA class (RR 1.81, 95% CI 0.91-3.6) in analysis of 3 trials with 412 patients, results limited by significant heterogeneity
      • no significant differences in
        • heart failure-related mortality in analysis of 4 trials with 879 patients
        • sudden cardiac death in analysis of 6 trials with 1,374 patients
      • Reference - Health Technol Assess 2014 Aug;18(56):1
    • CRT-D may reduce all-cause mortality and hospitalization for heart failure compared to ICD alone in patients with NYHA Class I-II heart failure (level 2 [mid-level] evidence)
      • based on systematic review of trials with methodologic limitations
      • systematic review of 5 randomized trials comparing CRT-D vs. ICD alone in 4,317 patients with NYHA Class I-II heart failure and left ventricular ejection fraction < 30%
      • inclusion criteria included
        • left ventricular ejection fraction ≤ 40% in 1 trial, ≤ 35% in 1 trial, and ≤ 30% in 3 trials
        • QRS interval ≥ 120 milliseconds in 3 trials and ≥ 130 milliseconds in 2 trials
      • follow-up ranged from 6 to 40 months
      • all trials had at least 1 of the following limitations
        • allocation concealment not stated or unclear
        • incomplete blinding
        • low event rates due to short follow-up (6 months)
      • comparing CRT-D to ICD alone, CRT-D associated with decreased
        • all-cause mortality in analysis of 5 trials with 4,317 patients
          • risk ratio (RR) 0.81 (95% CI 0.65-0.99)
          • NNT 24-834 with 12% all-cause mortality in ICD group
        • hospitalization for heart failure in analysis of 5 trials with 4,317 patients
          • RR 0.68 (95% CI 0.59-0.79)
          • NNT 14-27 with 18% hospitalization due to heart failure in ICD group
      • no significant difference in all-cause mortality in subgroup analysis of 3 trials with 402 patients with NYHA Class I heart failure
      • Reference - J Am Coll Cardiol 2011 Aug 23;58(9):935 full-text
    • insufficient evidence for reduced mortality with combined CRT-ICD therapy compared to either therapy alone
      • based on 2 meta-analyses
      • meta-analysis of 12 randomized trials with methodologic limitations including 8,307 patients with left ventricular dysfunction
      • meta-analysis of 4 randomized trials comparing CRT-ICD vs. ICD alone in 1,224 patients
        • possible reduction in all-cause mortality not statistically significant (relative risk [RR] 0.86, 95% CI 0.54-1.39)
        • degree of reduction similar to the statistically significant reduction in meta-analysis of 10 trials comparing CRT alone vs. medical therapy (RR 0.77, 95% CI 0.66-0.91)
        • 1 single trial (Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure [COMPANION] trial) showed statistically significant reduction in all-cause mortality (hazard ratio 0.64, 95% CI 0.48-0.86)
        • Reference - Ann Intern Med 2007 Aug 21;147(4):251, Evid Rep Technol Assess (Full Rep) 2007 Jun;(152):1
    • CRT-D associated with reduced risk of heart failure and mortality in women with LBBB at a shorter QRS duration than men with LBBB compared with ICD alone among patients with primarily NYHA Class II heart failure (level 2 [mid-level] evidence)
      • based on meta-analysis of individual patient data from 3 randomized trials
      • 4,076 patients (22% women) with heart failure (predominantly NYHA Class II) from 3 randomized trials evaluating CRT-D vs. ICD followed up to 3 years
      • left bundle branch block (LBBB) in 85% women and 68% men
      • all patients with LBBB stratified based on 10-millisecond QRS duration intervals
      • among patients with LBBB
        • for QRS duration 120-129 milliseconds, no significant differences in composite of heart failure event or death, or death alone comparing CRT-D vs. ICD alone in either men or women
        • for QRS duration 130-149 milliseconds in women, CRT defibrillator associated with reduced risk of
          • heart failure or death (hazard ratio [HR] 0.24, 95% CI 0.11-0.53)
          • death (HR 0.24, 95% CI 0.06-0.89)
        • for QRS duration ≥ 150 milliseconds, CRT defibrillator associated with significant reduction in composite of heart failure event or death, and death alone in both men and women
      • CRT-D not associated with benefit in men or women without LBBB, regardless of QRS duration
      • Reference - JAMA Intern Med 2014 Aug 1;174(8):1340, editorial can be found in JAMA Intern Med 2014 Aug 1;174(8):1348
    • CRT-D may reduce mortality and hospitalization for heart failure compared to ICD alone in patients with NYHA Class II or III heart failure and QRS duration ≥ 120 milliseconds (level 2 [mid-level] evidence)
      • based on randomized trial with protocol amendments during trial
      • 1,798 patients with NYHA Class II or III heart failure with left ventricular ejection fraction ≤ 30% and QRS duration ≥ 120 milliseconds despite optimal medical therapy randomized to combination CRT-D vs. ICD alone and followed for mean 40 months
      • protocol was amended halfway through enrollment period to include only patients with NYHA Class II after guideline changes in 2006
      • comparing CRT-D vs. ICD alone
        • death from any cause in 20.8% vs. 26.1% (p = 0.003, NNT 19)
        • death from cardiovascular cause in 14.5% vs. 17.9% (p = 0.02, NNT 30)
        • hospitalization for heart failure in 19.5% vs. 26.1% (p < 0.001, NNT 15)
        • 30-day device- or implantation-related complications in 13.2% vs. 6.8% (p < 0.001, NNH 15)
      • no significant difference in death from any cause or from cardiovascular cause in subgroup of 360 patients with NYHA Class III
      • CRT-D associated with lower composite of death and hospitalization in subgroup of 1,036 patients with QRS durations ≥ 150 milliseconds (p = 0.002)
      • Reference - RAFT trial (N Engl J Med 2010 Dec 16;363(25):2385), editorial can be found in N Engl J Med 2010 Dec 16;363(25):2456
      • CRT-D may reduce cardiovascular-related hospitalizations but increase implant- or device-related hospitalizations compared to ICD alone (level 2 [mid-level] evidence)
        • based on prespecified secondary analysis of randomized trial above
        • all patients were included in analysis
        • mean follow-up 41.2 months with CRT-D vs. 39.2 months with ICD alone
        • comparing CRT-D vs. ICD alone
          • cardiovascular-related hospitalizations per 100 patient-years 21.7 vs. 26.8 (p = 0.017)
          • implant- or device-related hospitalizations per 100 patient-years 8 vs. 5.4 (p < 0.001)
          • all-cause hospitalizations per 100 patient-years 47.2 vs. 52.3 (p = 0.042)
          • mean hospital stay per admission 8.8 days vs. 9.6 days (p = 0.005)
        • Reference - Circulation 2014 May 20;129(20):2021
      • CRT-D may not reduce mortality in patients with permanent atrial fibrillation (level 2 [mid-level] evidence)
        • based on pre-specified secondary analysis of randomized trial above
        • prespecified subgroup of 229 patients with heart failure and permanent atrial fibrillation at baseline were followed for mean 40 months
        • comparing CRT-D vs. ICD alone
          • all-cause death in 36.8% vs. 30.4% (not significant)
          • cardiovascular death in 22.8% vs. 20% (not significant)
          • hospitalization for heart failure in 19.3% vs. 27.8% (p = 0.052)
        • Reference - Circ Heart Fail 2012 Sep 1;5(5):566 full-text, editorial can be found in Circ Heart Fail 2012 Sep 1;5(5):547
  • CRT-D associated with reduced mortality and hospital readmission compared with ICD alone in patients with NYHA Class I-IV heart failure, left ventricular ejection fraction < 35%, and QRS duration ≥ 120 milliseconds (level 2 [mid-level] evidence)
    • based on retrospective cohort study
    • 7,090 propensity-matched patients > 65 years old with NYHA Class I-IV heart failure, LVEF < 35%, and prolonged QRS duration on electrocardiogram (≥ 120 milliseconds) had CRT-D or ICD alone and followed for 3 years
    • comparing CRT-D vs. ICD
      • mortality 25.7% vs. 29.8% (p < 0.001)
      • all-cause hospital readmission in 68.6% vs. 72.8% (p < 0.001)
      • cardiovascular hospital readmission in 45% vs. 52.4% (p < 0.001)
      • heart failure hospital readmission in 24.3% vs. 29.4% (p < 0.001)
      • device-related infection in 1.9% vs. 1% (p = 0.002)
    • lower risk of heart failure readmission associated with CRT with a defibrillator most pronounced in patients with left bundle branch block or QRS duration ≥ 150 milliseconds, and in women
    • Reference - Ann Intern Med 2014 May 6;160(9):603
  • CRT-D may reduce risk for nonfatal heart failure and may improve quality of life and NYHA class
    • CRT-D associated with reduced risk of nonfatal heart failure events compared to ICD alone in patients with NYHA Class I or II heart failure (level 2 [mid-level] evidence)
      • based on randomized trial with incomplete blinding and significant crossover in treatment groups
      • 1,820 patients with ejection fraction ≤ 30%, QRS duration ≥ 130 milliseconds, and NYHA Class I or II symptoms randomized to CRT-D vs. ICD alone and followed for mean 2.4 years
      • investigators deciding therapy or admission aware of group assignments
      • 12.4% in ICD-only group received CRT plus ICD device
      • comparing CRT-D vs. ICD alone
        • overall mortality 6.8% vs. 7.3% (not significant)
        • nonfatal heart failure event in 13.9% vs. 22.8% (p < 0.001, NNT 12)
      • similar findings in patients with ischemic and nonischemic cardiomyopathy
      • Reference - MADIT-CRT trial (N Engl J Med 2009 Oct 1;361(14):1329), editorial can be found in N Engl J Med 2009 Oct 1;361(14):1394
      • CRT-D may be more beneficial in women compared to men (level 2 [mid-level] evidence)
      • CRT-D associated with lower mortality compared to ICD alone in patients with left bundle-branch block but not in patients without left bundle-branch block (level 2 [mid-level] evidence)
        • based on subgroup analysis in follow-up of MADIT-CRT trial
        • 1,818 patients (70% left bundle-branch block) were followed for up to 7 years (median follow-up 5.6 years)
        • comparing CRT-D vs. ICD alone
          • all-cause mortality 18% vs. 29% (p = 0.002, NNT 9) in subgroup of patients with left bundle-branch block
          • all-cause mortality 35% vs. 35% (not significant) in subgroup of patients without left bundle-branch block
        • Reference - N Engl J Med 2014 May 1;370(18):1694, editorial can be found in N Engl J Med 2014 May 1;370(18):1751
      • CRT-D may reduce risk of heart failure events compared to ICD alone in patients with left bundle-branch block (level 2 [mid-level] evidence)
        • based on post hoc analysis of MADIT-CRT trial
        • 70% had left bundle-branch block (LBBB)
        • CRT-D associated with reduced risk of heart failure event (p < 0.001) in patients with LBBB (mean follow-up 29 months)
        • Reference - Circulation 2011 Mar 15;123(10):1061 full-text
      • CRT-D associated with improved quality of life compared to ICD alone in patients with LBBB but not patients without LBBB (level 2 [mid-level] evidence)
        • based on post hoc analysis of MADIT-CRT trial
        • 1,699 patients with quality of life assessments were followed for mean 2.4 years
        • CRT-D associated with improved quality of life in subgroup analysis of 1,204 patients with left bundle branch block (p < 0.01)
        • no significant difference in subgroup of 494 patients without left bundle branch block
        • Reference - J Am Coll Cardiol 2012 Nov 6;60(19):1940
      • left ventricular ejection fraction normalization after 12 months with CRT-D associated with reduced risk of ventricular arrhythmia, heart failure, or death (level 2 [mid-level] evidence)
        • based on post hoc secondary analysis of MADIT-CRT trial
        • 752 surviving patients (69%) in CRT-D group who had paired echocardiograms at enrollment and at 12 months were assessed
        • mean follow-up 2.2 years
        • patients were stratified by left ventricular ejection fraction (LVEF) recovery at 12 months
          • 13.7% had LVEF ≤ 35% (minimal or no improvement)
          • 79% achieved LVEF 36%-50% (subnormalization)
          • 7.3% achieved LVEF > 50% (normalization)
        • compared to LVEF ≤ 35%, LVEF > 50% associated with reduced risk of
          • ventricular arrhythmia (adjusted hazard ratio 0.24, 95% CI 0.07-0.82)
          • heart failure or death (adjusted hazard ratio 0.29, 95% CI 0.09-0.97)
        • consistent reductions in risks for LVEF 36%-50% compared to LVEF ≤ 35%
        • Reference - Circulation 2014 Dec 23;130(25):2278
    • CRT-D may improve quality of life and NYHA class compared to ICD alone in patients with moderate or severe heart failure, wide QRS complex, and history of arrhythmias requiring ICD placement (level 2 [mid-level] evidence)
      • based on randomized trial with high crossover rate
      • 369 patients with ejection fraction < 35%, QRS duration ≥ 130 milliseconds, high risk of life-threatening arrhythmias, and NYHA Class III-IV heart failure despite medical therapy had CRT-D device inserted and were randomized to CRT on vs. off for 6 months
      • 8% of patients switched from control to treatment group and 5% of patients switched from treatment to control group
      • CRT-D therapy associated with improved
        • quality of life score (p = 0.02)
        • NYHA functional heart failure class (p = 0.007)
      • no significant differences in survival, overall heart failure status, changes in left ventricular size or function, rates of hospitalization, or 6 minute walking distances,
      • Reference - JAMA 2003 May 28;289(20):2685 full-text
    • CRT-D may improve NYHA Class compared to dual-chamber ICD in patients with NYHA Class II or III heart failure and narrow QRS interval (level 2 [mid-level] evidence)
      • based on randomized trial without blinding of caregivers
      • 120 patients (mean age 67 years) with NYHA Class II or III heart failure and QRS interval ≤ 120 milliseconds randomized to implantation with CRT-D vs. dual-chamber ICD
      • all patients had ischemic cardiomyopathy, left ventricular ejection fraction ≤ 35%, and mechanical dyssynchrony
      • median follow-up 16 months
      • 111 patients who completed follow-up at 1 year were evaluated
      • comparing CRT-D vs. dual-chamber ICD
        • improved NYHA Class at 1 year in 45% vs. 24% (p = 0.02, NNT 5)
        • improved patient global status at 1 year in 54% vs. 33% (p = 0.027, NNT 5)
        • heart failure-related hospitalization in 9% vs. 20% (p = 0.097)
        • heart failure-related death in 4% vs. 9% (not significant)
        • all-cause death in 7% vs. 9% (not significant)
      • Reference - NARROW-CRT trial (Circ Arrhythm Electrophysiol 2013 Jun;6(3):538)
    • CRT-D may not improve exercise tolerance or left ventricular ejection fraction compared to ICD alone in patients with severe left ventricular dysfunction and QRS duration < 120 milliseconds (level 3 [lacking direct] evidence)
      • based on randomized trial without clinical outcomes and with early termination
      • 85 patients with left ventricular ejection fraction ≤ 35% and QRS duration < 120 milliseconds randomized to CRT-D vs. ICD alone for 12 months
      • trial terminated early at an unplanned analysis for futility and potential harm
      • no significant differences in exercise tolerance, ejection fraction, or left ventricular end-systolic volume
      • comparing CRT-D vs. ICD alone
        • change in 6-minute walk distance was -11.3 meters vs. +25.3 meters (p = 0.01)
        • increase in QRS duration of 40.2 milliseconds vs. 3.4 milliseconds (p < 0.0001)
        • heart failure-related hospitalization in 11% vs. 10% (not significant)
      • Reference - LESSER-EARTH trial (Circulation 2013 Feb 26;127(8):873 full-text)
    • CRT-D may improve NYHA Class compared to ICD alone in patients with advanced heart failure, QRS ≥ 120 milliseconds, but no evidence of mechanical dyssynchrony (level 2 [mid-level] evidence)
      • based on small randomized trial
      • 44 patients requiring ICD placement for advanced heart failure and without echocardiographic evidence of mechanical dyssynchrony were randomized to CRT-D vs. ICD alone
      • all patients met inclusion criteria of
        • NYHA Class III or IV heart failure (due to ischemic or nonischemic cardiomyopathy)
        • left ventricular ejection fraction ≤ 35%
        • QRS duration ≥ 120 milliseconds
        • left ventricular cavity dilatation (end diastolic dimension > 55 mm)
      • comparing CRT-D vs. ICD alone at 6 months
        • mean improvement in NYHA Class from baseline 0.9 vs. 0.5 (p = 0.01)
        • ≥ 1 mL/kg/minute increase in peak oxygen consumption (VO2max) in 50% vs. 21% (p = 0.055)
        • ≥ 1 mL/kg/minute deterioration in VO2max in 23% vs. 68% (p < 0.01, NNT 3)
      • no significant change in ejection fraction from baseline in either group
      • Reference - Heart 2011 Sep;97(17):1410
    • CRT-D may increase peak oxygen consumption compared to ICD alone in patients with heart failure and QRS interval ≥ 120 milliseconds (level 3 [lacking direct] evidence)
      • based on randomized trial without clinical outcomes
      • 172 patients with standard indication for ICD and QRS interval < 130 milliseconds randomized to CRT-D vs. ICD alone for 6 months
      • CRT-D associated with increased peak oxygen consumption in subgroup with QRS interval ≥ 120 milliseconds but not in subgroup with QRS interval < 120 milliseconds
      • Reference - N Engl J Med 2007 Dec 13;357(24):2461, commentary can be found in N Engl J Med 2008 Apr 24;358(17):1865

CRT-D in patients with ICD indication but without pacing indication

  • CRT-D dual-chamber pacing may not be beneficial and may be harmful in patients with indication for ICD but not cardiac pacing (level 2 [mid-level] evidence)
    • based on randomized trial without blinding of caregivers
    • 506 patients with indication for ICD, no indication for pacemaker, and left ventricular ejection fraction < 40% had ICD implantation and were randomized to CRT-D dual-chamber rate responsive (DDDR) pacing at 70 beats/minute vs. CRT-D ventricular backup pacing at 40 beats/minute
    • mean ejection fraction at baseline was 27%, but about half the patients were New York Heart Association (NYHA) functional Class I
    • median follow-up 8.4 months
    • trial stopped early because of nonsignificant increased likelihood of worse composite outcome
    • primary end point of death or hospitalization for heart failure reached by 83.9% DDDR pacing vs. 73.3% ventricular backup pacing group (NNH 9)
    • Reference - DAVID trial (JAMA 2002 Dec 25;288(24):3115 full-text), editorial can be found in JAMA 2002 Dec 25;288(24):3159
  • neither CRT-D atrial nor ventricular pacing appear clearly superior in patients with ICD indication but without pacing indication (level 2 [mid-level] evidence)
    • based on randomized trial without blinding of caregivers
    • 600 patients with impaired ventricular function, indication for ICD, and no indication for pacing were given CRT-D and randomized to atrial pacing (70 beats/minute) vs. minimal ventricular pacing (40 beats/minute)
    • mean follow-up 2.7 years
    • no significant differences in rates of
      • death or heart failure hospitalization
      • atrial fibrillation
      • syncope
      • appropriate or inappropriate shocks
      • quality of life
    • Reference - DAVID II trial (J Am Coll Cardiol 2009 Mar 10;53(10):872) full-text, editorial can be found in J Am Coll Cardiol 2009 Mar 10;53(10):881
  • CRT-D dual-chamber pacing associated with increased device-related complications compared to CRT-D single-chamber pacing, but hospitalization rates and mortality appear similar in patients without indications for pacing (level 2 [mid-level] evidence)
    • based on retrospective cohort study
    • 32,034 patients (mean age 74 years) with ICD (62% with dual-chamber device and 38% with single-chamber device) but without clear indications for pacing were analyzed
    • propensity score for likelihood of receiving dual-chamber ICD was calculated for each patient based on clinical, physician, and hospital factors
    • comparing CRT-D dual-chamber vs. CRT-D single-chamber in propensity-matched analysis with 23,238 patients
      • device-related complications in 4.7% vs. 3.5% (p < 0.001, NNH 83)
      • 1-year mortality 9.77% vs. 9.85% (not significant)
      • 1-year hospitalization for any cause in 44.8% vs. 43.9% (not significant)
      • heart failure hospitalization in 15.4% vs. 14.7% (not significant)
    • Reference - JAMA 2013 May 15;309(19):2025 full-text
  • CRT-D dual-chamber atrioventricular search hysteresis programming and CRT-D single-chamber backup pacing may have similar outcomes (level 2 [mid-level] evidence)
    • based on randomized trial with borderline statistical significance
    • 1,530 patients with ICD indication received CRT-D pacing with Vitality AVT ICD programmed to dual-chamber rate-responsive (DDDR) with atrioventricular search hysteresis (AVSH)/60-130 for 1 week
    • 988 patients who had < 20% right ventricular pacing after 1 week were randomized to DDDR AVSH vs. single-chamber (VVI-40) programming
    • mean follow-up 10.4 months
    • comparing DDDR AVSH vs. VVI-40 programming
      • heart failure death or hospitalization in 6.4% vs. 9.5% (p = 0.072)
      • all-cause mortality in 3.6% vs. 5.1% (not significant)
    • Reference - INTRINSIC RV trial (Circulation 2007 Jan 2;115(1):9 full-text)
    • higher mean intrinsic heart rate associated with greater risk of death or heart failure hospitalization
      • based on post hoc secondary analysis of 1,530 patients in randomized trial above
      • mortality or hospitalization for heart failure in
        • 5.8% with mean heart rate < 75 beats/minute
        • 20.9% with mean heart rate > 90 beats/minute
      • Reference - Circulation 2009 Nov 24;120(21):2040 full-text

Biventricular Pacing vs. Single Ventricular Pacing

  • biventricular pacing and left ventricular pacing may have similar functional outcomes in patients with chronic heart failure indication for CRT (level 2 [mid-level] evidence)
    • based on systematic review with wide confidence intervals
    • systematic review of 5 randomized trials comparing biventricular pacing vs. left ventricular pacing in 574 patients with chronic heart failure indication for CRT
    • outcomes measured at 2-12 months follow-up
    • 1 high-quality trial included in review summarized below
    • in all trials, biventricular pacing and left ventricular pacing each associated with significant improvement from baseline in clinical status and ventricular systolic function
    • no significant differences in
      • 6-minute walk distance in analysis of 4 trials with 268 patients (mean difference 11.25 meters favoring biventricular pacing, 95% CI -12.4 meters to +35 meters)
      • changes in New York Heart Association (NYHA) class in analysis of 4 trials with 268 patients
      • quality of life in analysis of 3 trials with 199 patients
      • peak oxygen consumption in analysis of 2 small trials with 51 patients (both trials lacked allocation concealment)
    • Reference - Am J Cardiol 2011 Oct 15;108(8):1160
  • biventricular pacing and left ventricular pacing have similar complication rates and functional outcomes in patients with NYHA Class III or IV heart failure (level 1 [likely reliable] evidence)
    • based on randomized noninferiority trial
    • 176 patients with NYHA Class III or IV heart failure despite optimal medical therapy scheduled for CRT device randomized to biventricular pacing vs. left ventricular pacing
    • noninferiority margin defined as ≤ 20% lower response rate with biventricular pacing vs. left ventricular pacing
    • no significant differences at 6 months in
      • ≥ 1 point decrease in NYHA functional status
      • ≥ 5 mm decrease in left ventricular end-systolic diameter
      • complication-free survival
      • hospitalization
      • mortality
      • arrhythmias
    • both techniques associated with significant improvement in quality of life scores, distance in 6-minute walk test, and left ventricular ejection fraction from baseline (p < 0.001)
    • Reference - B-LEFT HF trial (Am Heart J 2010 Jun;159(6):1052)
  • biventricular antitachycardia CRT-D pacing may have similar termination of ventricular tachyarrhythmias as right ventricular antitachycardia CRT-D pacing in patients with ICD for heart failure (level 3 [lacking direct] evidence)
    • based on randomized trial without clinical outcomes
    • 526 patients with ICD for heart failure randomized to biventricular vs. right ventricular antitachycardia CRT-D pacing (single burst 8 pulse, 88% coupling interval) and followed for up to 12 months
    • no significant differences in termination of ventricular tachyarrhythmias
    • biventricular CRT-D pacing associated with more rapid termination of fast ventricular tachycardia in subgroup of patients with coronary artery disease (p = 0.032)
    • Reference - ADVANCE CRT-D trial (Am Heart J 2010 Jun;159(6):1116)

Considerations for CRT in Patients with Atrial Fibrillation

  • atrial fibrillation is the most common arrhythmia in patients with heart failure (45% patients with heart failure reported to also have atrial fibrillation)(3)
  • patients with permanent atrial fibrillation benefit substantially less than those without(1)
  • CRT most beneficial for patients with atrial fibrillation who have had atrioventricular nodal ablation(1)
  • CRT suggested if
  • CRT may be considered if otherwise indicated (CCS Weak recommendation, Low-quality evidence)(4)
  • adding atrioventricular junction ablation suggested in patients with incomplete biventricular pacing (ESC Class IIa, Level B)(3)
  • atrial fibrillation associated with increased mortality and lower response rate in patients with heart failure, left ventricle ejection fraction ≤ 35%, and QRS interval > 120 milliseconds having CRT (level 2 [mid-level] evidence)
    • based on systematic review of observational studies
    • systematic review of 23 observational studies comparing outcomes in patients with atrial fibrillation vs. without atrial fibrillation in 7,495 patients with heart failure, left ventricle ejection fraction ≤ 35%, and QRS interval > 120 milliseconds who had CRT
    • mean follow-up 33 months
    • atrial fibrillation associated with
      • increased risk of nonresponse to CRT in analysis of 7 studies with 1,663 patients
        • pooled nonresponse rate 34.5% with atrial fibrillation and 26.7% without atrial fibrillation
        • relative risk (RR) 1.32 (95% CI 1.12-1.55)
      • increased all-cause mortality in analysis of 9 studies with 2,765 patients, results limited by significant heterogeneity
        • pooled annual all-cause mortality 10.8% with atrial fibrillation and 7.1% without atrial fibrillation
        • RR 1.5 (95% CI 1.08-2.09)
    • Reference - Heart Rhythm 2011 Jul;8(7):1088, commentary can be found in Heart Rhythm 2011 Jul;8(7):1095
  • atrioventricular nodal ablation may improve survival compared to drug therapy in patients with heart failure receiving cardiac resynchronization therapy (level 2 [mid-level] evidence)
    • based on 2 cohort studies
    • 154 patients with atrial fibrillation and heart failure had atrioventricular nodal ablation or drug therapy for rate control during cardiac resynchronization therapy (CRT)
      • comparing atrioventricular nodal ablation vs. drug therapy
        • 2-year survival 96% vs.76.5% (p = 0.008)
        • greater improvement in New York Heart Association (NYHA) Class (p = 0.04)
        • no significant differences in left ventricular ejection fraction or left ventricular end-diastolic diameter
      • Reference - Heart Rhythm 2010 Sep;7(9):1240
    • 243 patients with heart failure and permanent atrial fibrillation had CRT and either atrioventricular junction ablation or negative chronotropic drugs
      • median follow-up 34 months
      • compared with pharmacologic rate control, atrioventricular junction ablation associated with
        • decreased mortality rate (adjusted hazard ratio [HR] 0.26, 95% CI 0.09-0.73)
        • decreased cardiac mortality rate (adjusted HR 0.31, 95% CI 0.10-0.99)
        • decreased heart failure mortality rate (adjusted HR 0.15, 95% CI 0.03-0.70)
      • Reference - Eur Heart J 2008 Jul;29(13):1644 full-text, commentary can be found in Eur Heart J 2008 Sep;29(17):2182 full-text
  • atrioventricular junction ablation may increase cardiac mortality risk for heart failure patients with atrial fibrillation treated with CRT (level 2 [mid-level] evidence)
    • based on subgroup analysis of retrospective cohort study
    • 131 patients with heart failure and CRT reviewed
    • 53 patients with atrial fibrillation and heart failure reviewed (26 had A-V nodal ablation, 27 did not)
    • compared with no ablation, atrioventricular junction ablation group had increased cardiac mortality risk (hazard ratio 5.22, 95% CI 1.6-17.01)
    • Reference - Europace 2008 Jul;10(7):809 full-text, editorial can be found in Europace 2008 Jul;10(7):779 full-text
  • atrioventricular junction ablation may increase rate of resumption of sinus rhythm in patients with permanent atrial fibrillation having CRT (level 3 [lacking direct] evidence)
    • based on retrospective cohort study without clinical outcomes
    • 330 heart failure patients with atrial fibrillation and CRT treatment reviewed
    • 10% had sinus rhythm resumption after CRT at median 4 months
    • atrioventricular junction ablation associated with increased rate of resumption of sinus rhythm (hazard ratio 4.27, 95% CI 1.54-11)
    • Reference - Eur Heart J 2010 Apr;31(8):976 full-text
  • atrioventricular junction ablation reported to be associated with improvements in ejection fraction and exercise performance in heart failure patients with permanent atrial fibrillation treated with CRT (level 3 [lacking direct] evidence)
    • based on cohort study without clinical outcomes
    • cohort of patients with heart failure and ventricular conduction disturbances receiving CRT included
      • 48 patients with permanent atrial fibrillation with ventricular rate controlled by drugs, apparent biventricular pacing > 85% of pacing time
      • 114 patients with permanent atrial fibrillation who had atrioventricular junction ablation, 100% resynchronization therapy delivery
    • atrial fibrillation patients treated with atrioventricular junction ablation had significant improvements in ejection fraction, exercise tolerance (6-minute walk test or symptom limited peak O2 consumption during exercise), and reverse remodeling effect
    • patients treated with pharmacologic rate control not associated with significant improvements on outcomes
    • Reference - J Am Coll Cardiol 2006 Aug 15;48(4):734, editorial can be found in J Am Coll Cardiol 2006 Aug 15;48(4):744
  • optimized echo-guided cardiac resynchronization therapy (CRT) reduces worsening heart failure compared to conventional right ventricular pacing in heart failure patients having atrioventricular junction ablation for permanent atrial fibrillation (level 1 [likely reliable] evidence)
    • based on randomized trial
    • 186 patients with successful atrioventricular junction ablation and CRT device implantation were randomized to optimized echo-guided CRT vs. right ventricular apical pacing
    • median follow-up 20 months
    • comparing echo-guided CRT vs. right ventricular apical pacing
      • worsening heart failure (leading to symptoms and signs, hospitalization, or death) in 11% vs. 26% (p = 0.005, NNT 7 for CRT)
      • death from heart failure in 3.1% vs. 4.5% (not significant)
      • hospitalization due to heart failure in 3 patients (7 hospitalizations) vs. 12 patients (15 hospitalizations) (p = 0.013)
    • Reference - Eur Heart J 2011 Oct;32(19):2420 full-text, editorial can be found in Eur Heart J 2011 Oct;32(19):2344 full-text

Considerations for CRT in Patients with Conduction Abnormalities

  • CRT suggested for patients with new onset, high degree atrioventricular block that requires chronic right ventricular pacing who have (CCS Conditional recommendation, Moderate-quality evidence)(5)
    • signs and/or symptoms of heart failure
    • LVEF ≤ 45%
  • dual-chamber (atrioventricular) pacing improves heart failure symptoms and reduces risk for atrial fibrillation compared to ventricular pacing in patients with sinus-node dysfunction with heart failure (level 1 [likely reliable] evidence)
    • based on randomized trial
    • 2,010 patients with sinus-node dysfunction randomized to dual-chamber (atrioventricular) pacing vs. ventricular pacing, with median follow-up 33 months (approximately 20% of patients had a history of heart failure at baseline)
    • dual-chamber pacing associated with
      • lower risk of atrial fibrillation (hazard ratio [HR] 0.79, 95% CI 0.66-0.94, NNT 17.5)
      • better heart failure scores (p < 0.001)
      • lower incidence of hospitalization for heart failure (adjusted HR 0.73, 95% CI 0.56-0.95, statistically significant for adjusted HR only)
      • over a 4-year period dual-chamber pacing provided statistically significant improvement in health-related quality of life for 6 of 8 indicators (Short-Form General Health Survey [SF]-36 subscales) compared with ventricular pacing
    • no differences in rates of death (19.7% vs. 20.5%) or stroke (4% vs. 4.9%)
    • Reference - N Engl J Med 2002 Jun 13;346(24):1854 full-text, commentary can be found in N Engl J Med 2002 Dec 5;347(23):1891
  • biventricular pacing may reduce hospitalization for heart failure compared to right ventricular pacing in patients with atrioventricular block and NYHA Class I-III heart failure (level 2 [mid-level] evidence)
    • based on randomized trial with differential crossover rates
    • 691 patients (mean age 73 years) with atrioventricular (AV) block and New York Heart Association (NYHA) Class I-III heart failure were randomized to biventricular pacing vs. right ventricular pacing
      • 70% received pacemaker and 30% received implantable cardioverter defibrillator
      • all patients had left ventricular ejection fraction ≤ 50%
    • mean follow-up 37 months
    • primary outcome was any of all-cause death, urgent care visit for heart failure requiring IV therapy, or ≥ 15% increase in left ventricular end-systolic volume index (volume index data unavailable for 22.2%)
    • 3.7% with biventricular pacing and 24.6% with right ventricular pacing crossed over to other treatment (60% of crossovers in right ventricular pacing group occurred after primary outcome event)
    • comparing biventricular pacing vs. right ventricular pacing
      • hospitalization for heart failure in 21.8% vs. 26.3% (hazard ratio 0.7, 95% CI 0.52-0.93)
      • mortality 21.5% vs. 26.3% (not significant)
      • primary outcome in 45.8% vs. 55.6% (p < 0.05) in analysis of 350 patients with complete outcome data
    • Reference - BLOCK HF trial (N Engl J Med 2013 Apr 25;368(17):1585)
    • biventricular pacing may improve clinical outcomes compared to right ventricular pacing in patients with atrioventricular block and NYHA Class I-III heart failure (level 2 [mid-level] evidence)
      • based on secondary analysis of BLOCK HF trial
      • all patients were classified by Packer clinical composite score as worsened, improved, or no change
        • worsened defined as death, heart failure hospitalization, discontinued therapy due to worsening heart failure, increase in NYHA functional class or worsening symptoms by self report
        • improved defined as decrease in NYHA functional class or improved symptoms by self report
      • clinical composite score based on clinical outcomes, patient symptoms, and heart failure status
      • 691 patients were evaluated for NYHA functional class and quality of life at 6, 12, 18, and 24 months
      • Bayesian statistical analysis used to give posterior probabilities (PP) of differences in outcomes with PP > 95% considered statistically significant
      • clinical composite scores comparing biventricular vs. right ventricular pacing at 24 months (PP = 99.8%)
        • worsened in 39% vs. 51%
        • improved in 38.3% vs. 29.9%
        • no change in 22.7% vs. 18%
      • consistent results at other timepoints
      • biventricular pacing associated with
        • significant improvement in NYHA functional class at 12 months, but not at later timepoints
        • significant improvement in quality of life at 6 and 12 months, but not at later timepoints
      • Reference - J Am Coll Cardiol 2016 May 10;67(18):2148 full-text
  • biventricular pacing may improve NYHA functional Class, left ventricular function, exercise capacity, and quality of life compared to right ventricular pacing in patients with symptomatic bradycardia, impaired AV conduction, and left ventricular dysfunction (level 2 [mid-level] evidence)
    • based on single blinded randomized crossover trial
    • 30 patients with symptomatic bradycardia and impaired AV conduction indication for permanent ventricular pacing and left ventricular dysfunction (left ventricular end-diastolic diameter ≥ 60 mm and ejection fraction ≤ 40%) received 3 months each of right ventricular and biventricular pacing in random order
    • 80% received CRT device and 20% with permanent atrial fibrillation received cardiac resynchronization therapy with defibrillator (CRT-D) device
    • biventricular pacing associated with
      • improved NYHA functional Class (mean 1.1, p < 0.001)
      • reduced left ventricular end-diastolic (-9%, p = 0.022) and end-systolic volumes (-16.9%, p < 0.001)
      • reduced N-terminal pro-B-type natriuretic peptide (NT-proBNP) level (-31%, p < 0.002)
      • reduced Minnesota Living with Heart Failure score (-18.9%, p = 0.01)
      • increased left ventricular ejection fraction (+22.1%), peak oxygen consumption (+12%), oxygen uptake (+12.5%), and peak circulatory power (+21%) (p < 0.0002 for all)
      • results similar for patients with and without atrial fibrillation
    • Reference - J Am Coll Cardiol 2006 May 16;47(10):1927

Factors Associated with CRT Response

  • L2ANDS2 score may help predict 6-month response to CRT in patients with heart failure (level 2 [mid-level] evidence)
    • based on prognostic cohort study with limited data regarding performance in validation cohort
    • derivation cohort included 162 patients (mean age 65 years) with heart failure referred for cardiac resynchronization therapy (CRT) device implantation and followed for 6 months
    • validation cohort included 45 patients (mean age 68 years) with heart failure referred for CRT device implantation at different institution and followed for 6 months
    • validation cohort had greater proportion of men and patients had greater New York Heart Association (NYHA) functional class, higher heart rate, and lower left ventricular pre-ejection interval and filling time (p ≤ 0.02 for all)
    • good response to CRT defined as ≥ 15% reduction in left ventricular end-systolic volume on echocardiography
    • 60% in derivation cohort and 71% in validation cohort had good response 6 months after device implantation
    • L2ANDS2 score derived using baseline clinical, electrocardiographic, and echocardiographic factors associated with good response to CRT (total score 0-7 points)
      • 2 points for left bundle branch block
      • 1 point for age > 70 years
      • 1 point for nonischemic origin
      • 1 point for left ventricular end-diastolic diameter < 40 mm/m2
      • 2 points for septal flash
    • for prediction of good response to CRT in derivation cohort, L2ANDS2 score > 4 had sensitivity 72% and specificity 72%
    • discrimination of L2ANDS2 score in validation cohort reported to be similar to derivation cohort, but sensitivity and specificity in validation not reported
    • Reference - Am J Cardiol 2014 Jun 15;113(12):2045
  • presence of left bundle-branch block plus QRS duration ≥ 150 milliseconds associated with decreased mortality and hospital readmission compared to left bundle-branch block with shorter QRS duration and to no left bundle-branch block after CRT-D implantation in patients with heart failure
    • based on retrospective cohort study
    • 24,169 patients ≥ 65 years old (mean age 75 years) with heart failure who had implant of CRT-D were analyzed
      • 67% had left bundle-branch block (LBBB)
      • 55% had QRS duration ≥ 150 milliseconds
    • 3-year mortality
      • 20.9% of 9,899 patients with LBBB and QRS duration ≥ 150 milliseconds (p < 0.05 vs. each other group)
      • 26.5% of 6,259 patients with LBBB and QRS duration < 150 milliseconds (120 milliseconds-149 milliseconds)
      • 30.7% of 3,306 patients without LBBB and with QRS duration ≥ 150 milliseconds
      • 32.3% of 4,715 patients without LBBB and with QRS duration < 150 milliseconds
    • 1-year readmission rates for any cause, for cardiovascular cause, and for heart failure were also significantly lower in patients with LBBB and QRS duration ≥ 150 milliseconds compared to other groups
    • Reference - JAMA 2013 Aug 14;310(6):617
  • higher pulse pressure at 1 year after CRT-D implantation associated with reduced risk of heart failure or death at 2 years in patients with mild symptomatic heart failure and LBBB
    • based on cohort analysis of data from randomized trial
    • 754 patients (mean age 64 years, 68% male) from MADIT-CRT trial with mild symptomatic heart failure (NYHA class I or II) with left ventricular ejection fraction (LVEF) ≤ 35% and LBBB who had implant of CRT-D were stratified by pulse pressure at baseline and at 1 year after implantation
    • mean follow-up 2.4 years
    • pulse pressure ≥ 41 mm Hg at baseline associated with significantly greater improvement in left ventricular echocardiographic parameters vs. pulse pressure ≤ 40 mm Hg at baseline, but no significant differences in composite of heart failure and death
    • each 10 mm Hg increase in pulse pressure at 1 year after implantation associated with
      • reduced 2-year risk of heart failure or death (adjusted hazard ratio 0.78, 95% CI 0.66-0.92)
      • reduced 2-year risk of death (adjusted hazard ratio 0.68, 95% CI 0.52-0.87)
    • Reference - Am J Cardiol 2014 Oct 1;114(7):1053
  • enlarged left atrial volume at implantation associated with increased risk of death in patients with mild heart failure having CRT
    • based on cohort analysis of data from randomized trial
    • 1785 patients (mean age 65 years) who received CRT-D or implantable cardioverter defibrillator (ICD) alone in MADIT-CRT trial were assessed for left atrial volume at baseline and 1 year after implantation and followed for up to 3.5 years
      • patients had either ischemic cardiomyopathy with NYHA class I to II heart failure or nonischemic cardiomyopathy with NYHA class II, QRS duration ≥ 130 ms, and ejection fraction ≤ 0.3
      • enlarged left atrial volume (LAV) defined as > 52 mL/m2 (> 75th percentile)
    • compared to patients with lower LAV, enlarged LAV at implantation associated with
      • increased risk of death (adjusted hazard ratio [HR] 1.59, 95% CI 1.08-2.35)
      • increased risk in death or heart failure (adjusted HR 1.69, 95% CI 1.35-2.11)
    • each 1% reduction in LAV from baseline to 1 year associated with 4% reduction in risk of heart failure or death
    • no significant association between left ventricular end systolic volume and risk of death or heart failure after adjustment for LAV
    • Reference - Circ Heart Fail 2014 Jan;7(1):154 full-text

Preprocedure Considerations

  • recommended general preprocedure considerations include
    • ensure all CRT candidates have stable heart failure status on guideline-directed medical care before implantation(6)
    • develop pre-implant strategy to identify and manage comorbidities that may reduce CRT response, such as(6)
      • atrial fibrillation
      • frequent premature ventricular contractions
  • recommended preprocedure tests include
    • comprehensive echocardiogram to quantify left ventricular ejection fraction and assess cardiac size and function(6)
    • 12-lead electrocardiogram with QRS measure and morphology characterization(6)
    • coronary sinus venography to guide lead selection and assist navigation (may be performed during procedure)(6)
  • suggested preprocedure tests include
    • formal functional status testing with quality of life measure to monitor CRT response(6)
    • venous anatomic mapping with computed tomography angiography in patients with(6)
      • prior LV lead implant failure
      • risk for abnormal venous anatomy
  • for patients with high thromboembolic risk receiving anticoagulant therapy with warfarin(6)
    • continuing warfarin anticoagulation perioperatively with reduced dose and close monitoring of international normalized ratio (INR) with target INR 2-3 recommended
    • postoperative heparin use discouraged
  • for patient with low to moderate thromboembolic risk taking oral anticoagulant(6)
    • using warfarin, continuing therapy at reduced dose (INR 1.5-2) or discontinuing therapy 3-5 days before implantation to minimize bleeding risk suggested
    • using direct thrombin or factor Xa inhibitor agents, discontinuing therapy 2-3 days before implantation to minimize bleeding risk suggested

Procedure Considerations

  • CRT upgrade recommendations(5)
    • CRT upgrade can be challenging due to
      • partial or total venous occlusion
      • resistance along left ventricle (LV) lead course from existing leads
      • scar tissue
    • venoplasty or lead extraction may be required to facilitate transvenous LV lead placement if venous occlusion present
    • ipsilateral contrast injection from a peripheral vein or referral to a more experienced implantation center may be helpful in planning procedure
    • more complex implantations should be performed in experienced centers with low complication rates
  • lead placement recommendations
    • right ventricle lead should be first intracardiac lead implanted(6)
    • perform left ventricle lead testing to ensure adequate safety margin for capture and avoidance of phrenic nerve stimulation(6)
    • right ventricular (RV) lead placement(4)
      • is based on lead performance, potential interaction with other leads, and future removal
      • no reliable data published for optimum right ventricle lead placement
    • left ventricular (LV) lead placement
      • successful LV lead placement determined by(5)
        • adequate threshold for pacing
        • avoiding capture of nearby phrenic nerve
        • stable leads
      • in patients with nonischemic LV dysfunction and left bundle branch block (LBBB), latest LV activation typically lateral or posterior but may be different in patients with ischemic LV dysfunction(5)
      • optimum placement appears to be(5)
        • large in patients with nonischemic LV dysfunction
        • restricted and variable in patients with ischemic LV dysfunction or non-LBBB patterns
      • cardiac magnetic resonance imaging (MRI) may be reliable and specific for identifying optimum LV placement location(5)
  • recommended post implantation evaluation(6)
    • device interrogation
    • chest X-ray
    • surface electrocardiogram
    • careful attention to volume status due to diuresis from acute response to CRT
    • standard echocardiogram if anticipate complication due to symptoms or clinical findings
    • assessment to ensure 100% biventricular capture
    • overnight hospitalization for observation
  • recommendations for patients having other procedures(5)

Follow-up

  • follow-up recommendations
    • suggested in-person follow-up frequency(2)
      • within 72 hours of device implantation
      • 2-12 weeks after device implantation
      • every 3-12 months after device implantation (can be remote)
      • every 3-6 months after device implantation for CRT-D (can be remote)
      • annually until battery depletion
    • encourage patient to initiate a remote transmission in event of new symptoms(6)
    • follow-up visits should include(6)
      • history and physical
      • device interrogation and testing
      • systematic analysis of device data
      • evaluation of left ventricle function or other adjuncts to assess heart failure progression
      • optimization of medical therapy
      • assuring adequate and consistent biventricular pacing
      • treatment of arrhythmias
    • maximize CRT response with upward titration of heart failure medications(6)
    • clinical condition may improve after CRT, optimize medications by introducing drugs not tolerated before CRT or increasing dose(5)
    • if patient has atrial fibrillation with native conduction and CRT not delivered consistently, catheter ablation of atrioventricular node suggested(6)
    • reassess patient's CRT needs after pulse generator replacement(5)
    • discontinuation of CRT by programming off LV stimulation may be considered if(6)
      • no CRT response evident
      • concern exists that LV pacing is introducing risk to patient
    • progressive heart failure may require referral for cardiac transplantation and/or mechanical circulatory support(5, 6)
  • recommendations for evaluating CRT response include
    • assessment of symptoms and functional response(6)
    • echocardiographic assessment for cardiac function(6)
    • for patients who do not improve in heart failure status, assessment of potentially reversible causes(6)
    • device interrogation to assess(6)
      • atrial and ventricular arrhythmias
      • quality of CRT delivery (% effective biventricular capture)
      • rate response
    • assessment of comorbidities, such as atrial arrhythmias with poorly controlled ventricular rate ( will reduce CRT response)(5)
    • assess for loss of left ventricle pacing due to lack or capture or lead dislodgement (will reduce CRT response)(5)
    • use of 12-lead electrocardiography to compare QRS morphology before and after CRT implantation(5)
    • chest radiograph for determining LV lead placement and changes in position(5)
    • consideration for optimizing atrioventricular and interventricular timing in select patients, but may not be beneficial(5, 6)
    • consideration of LV lead repositioning in select patients, but may not be beneficial(6)
  • remote monitoring
    • for patients with implantable loop recorder, follow-up every 1-6 months (in person or remote) suggested based on symptoms and indications(2)
    • for patients with implantable hemodynamic monitor, follow-up every 1-6 months (in person or remote) suggested based on indication (assess more frequently when clinically indicated)(2)
    • implant-based multiparameter telemonitoring reduces all-cause mortality in patients with heart failure and reduced ejection fraction (level 1 [likely reliable] evidence)
      • based on randomized trial
      • 716 patients (mean age 66 years) with chronic heart failure and recent implantation of dual-chamber CRT-D (in 59%) or ICD (in 41%) were randomized to implant-based multiparameter telemonitoring vs. no telemonitoring and followed for 1 year
        • implant-based multiparameter telemonitoring consisting of implanted devices transmitting diagnostic data once daily or upon tachyarrhythmia with clinical response at discretion of investigators
        • all patients received usual care
      • at baseline, all patients had New York Heart Association class II-III symptoms with ejection fraction ≤ 35%, were receiving optimal drug treatment, and had no permanent atrial fibrillation
      • comparing implant-based multiparameter telemonitoring vs. no telemonitoring
        • mortality 3% vs. 8.2% (p = 0.004, NNT 20)
        • overnight hospitalization for heart failure in 6.9% vs. 8.2% (not significant)
      • no significant differences in rates of worsening NYHA functional class or in moderate-to-severe worsening of patient global assessment
      • Reference - IN-TIME trial (Lancet 2014 Aug 16;384(9943):583), editorial can be found in Lancet 2014 Aug 16;384(9943):560

Prevention of Complications

  • contrast induced nephropathy(5)
    • reported incidence 7%-43%
    • suggested prevention methods include
      • prehydration
      • lower diuretic dose
      • lower dose or dilution of contrast
  • lead related complications(5)
    • reported incidence 3.5%-18.7%
    • suggested prevention methods include appropriate training with sufficient number of procedures
  • pneumothorax(5)
    • reported incidence 0.6%-1%
    • suggested prevention methods include
      • extrathoracic puncture
      • echo-guided or contrast-guided venous puncture
      • axillary puncture instead of subclavian
      • use of cephalic vein
  • pericardial effusion(5)
    • reported incidence 1.5%
    • suggested prevention methods include using soft-tip guides and access tools
  • hematoma(5)
    • reported incidence 3%-6%
    • suggested prevention methods include avoiding low molecular weight heparin before implantation
  • phrenic nerve stimulation(5)
    • reported incidence up to 13%
    • suggested prevention methods include
      • conscious sedation
      • avoiding paralytic agents
      • identifying all available coronary vein branches
      • useing multipolar leads (additional electrodes)
  • device related infections(5)
    • reported incidence 1.3%-2.6%
    • suggested prevention methods include
      • use of appropriate prophylactic antibiotic before skin incision
      • use of chlorhexidine to prepare skin
      • limiting shaving
    • American Heart Association (AHA) recommendations for diagnosing and managing Cardiovascular Implantable Electronic Device (CIED) infections
      • recommendations for antimicrobial prophylaxis at time of CIED implantation
      • recommendations for diagnosing CIED infection
        • obtain ≥ 2 sets of blood cultures at initial evaluation before prompt initiation of antimicrobial therapy for infection (AHA Class I, Level C)
        • obtain generator-pocket tissue Gram stain and culture and lead-tip culture when device explanted (AHA Class I, Level C)
        • perform transesophageal echocardiography (TEE) for
          • CIED infection or valvular infective endocarditis if positive blood cultures or negative blood cultures but recent microbial therapy prior to obtaining blood cultures (AHA Class I, Level C)
          • evaluating left-sided heart valves, even if transthoracic views demonstrate lead-adherent masses, if infective endocarditis suspected (transthoracic echocardiography may be sufficient for pediatric patients with good views) (AHA Class I, Level B)
        • refer to cardiologist or infectious disease specialist if patient develops fever or bloodstream infection without known cause (AHA Class IIa, Level C)
        • percutaneous aspiration of generator pocket not recommended as part of diagnostic evaluation (AHA Class III, Level C)
      • recommendations for removing CIED in patients with infection
        • complete removal of device and lead is recommended for all patients with
          • definitive infection evidenced by valvular and/or lead infective endocarditis or sepsis (AHA Class I, Level A)
          • device pocket infection evidence by any of (AHA Class I, Level B)
            • abscess formation
            • device erosion
            • skin adherence
            • chronic draining sinus without definite involvement of leads and/or device
          • valvular endocarditis without definite involvement with lead and/or device (AHA Class I, Level B)
          • occult staphylococcal bacteremia (AHA Class I, Level B)
        • complete removal of device is reasonable in patients with persistent occult gram-negative bacteremia despite appropriate antibiotic therapy (AHA Class IIa, Level B)
        • complete removal of device is not indicated for
          • superficial or incisional infection without involvement of device and/or leads (AHA Class III, Level C)
          • relapsing bloodstream infection due to source other than device and requiring long-term suppressive antimicrobials (AHA Class III, Level C)
      • recommendations for antimicrobial treatment of CIED infection
        • select antimicrobial therapy based on identification and in vitro susceptibility of infecting pathogen (AHA Class I, Level B)
        • give antimicrobial therapy for
          • 10-14 days after device removal for pocket infection (AHA Class I, Level C)
          • ≥ 14 days after device removal for bloodstream infection (AHA Class I, Level C)
          • ≥ 4-6 weeks for complicated infection such as infective endocarditis, septic thrombophlebitis, osteomyelitis, or if bloodstream infection persists (AHA Class I, Level C)
      • recommendations for long-term use of suppressive antimicrobial therapy of CIED Infection
        • consider long-term suppressive therapy for patients who had CIED infection but are not candidates for complete device removal (AHA Class IIb, Level C)
        • do not give long-term suppressive therapy to patients who are candidates for infected device removal (AHA Class III, Level C)
      • recommendations for CIED replacement implantation after removal of infected CIED
        • carefully evaluate patient to determine if continued need for device (AHA Class I, Level C)
        • do not implant replacement device ipsilateral to extraction site but instead in preferred alternative locations, such as contralateral side, iliac vein, or epicardial implantation (AHA Class I, Level C)
        • if blood culture positive before previous device extraction, obtain blood culture after device removal and be sure blood culture negative > 72 hours before implanting replacement device (AHA Class IIa, Level C)
        • delay new transvenous lead placement for ≥ 14 days after device removal when there is evidence of valvular infection (AHA Class IIa, Level C)
      • Reference - Circulation 2010 Jan 26;121(3):458 full-text

Guidelines and Resources

Guidelines

International guidelines

  • European Heart Rhythm Association/European Society of Cardiology/Heart Rhythm Society/Heart Failure Society of America/American Society of Echocardiography/American Heart Association/European Association of Echocardiography/Heart Failure Association (EHRA/ESC/HRS/HFSA/ASE/AHA/EAE/HFA) expert consensus statement on cardiac resynchronization therapy in heart failure: implant and follow-up recommendations and management can be found in Heart Rhythm 2012 Sep;9(9):1524, Europace 2012 Sep;14(9):1236 full-text or at National Guideline Clearinghouse 2013 Jun 24:39222
  • Heart Rhythm Society/European Heart Rhythm Association (HRS/EHRA) expert consensus on monitoring of Cardiovascular Implantable Electronic Devices (CIED) can be found in Heart Rhythm 2008 Jun;5(6):907
  • International Society for Holter and Noninvasive Electrocardiology/European Heart Rhythm Association (ISHNE/EHRA) expert consensus on remote monitoring of cardiovascular implantable electronic devices (CIEDs) can be found in Ann Noninvasive Electrocardiol 2012 Jan;17(1):36

United States guidelines

  • American College of Cardiology/American Heart Association (ACC/AHA) 2005 guideline update on diagnosis and management of chronic heart failure in adults can be found in J Am Coll Cardiol 2005 Sep 20;46(6):e1 full-text
  • Heart Failure Society of America (HFSA) guideline on indications for cardiac resynchronization can be found in J Card Fail 2012 Feb;18(2):94
  • Heart Rhythm Society/Pediatric and Congenital Electrophysiology Society (HRS/PACES) clinical competency statement on training pathways for implantation of cardioverter-defibrillators and cardiac resynchronization therapy devices in pediatric and congenital heart patients can be found in Heart Rhythm 2008 Jun;5(6):926
  • HFSA 2010 guideline section on electrophysiology testing and use of devices in heart failure can be found at HFSA 2010 PDF

United Kingdom guidelines

  • Scottish Intercollegiate Guidelines Network (SIGN) national clinical guideline on management of chronic heart failure can be found at SIGN 2016 Mar PDF

Canadian guidelines

  • Canadian Cardiovascular Society/Canadian Anesthesiologists' Society/Canadian Heart Rhythm Society (CCS/CAS/CHRS) joint position statement on perioperative management of patients with implanted pacemakers, defibrillators, and neurostimulating devices can be found in Can J Cardiol 2012 Mar-Apr;28(2):141 full-text

European guidelines

  • European Heart Rhythm Association (EHRA) expert consensus statement on management of cardiovascular implantable electronic devices in patients nearing end of life or requesting withdrawal of therapy can be found in Europace 2010 Oct;12(10):1480
  • Italian expert consensus on remote monitoring of cardiac implantable electronic devices: technology, indications, organizational models, acceptability, responsibility, and economic issues can be found in G Ital Cardiol (Rome) 2011 Jun;12(6):450 [Italian]

Review articles

Patient Information

ICD-9/ICD-10 Codes

ICD-9 codes

  • V45.01 cardiac pacemaker in situ
  • V45.02 automatic implantable cardiac defibrillator in situ
  • V53.3 fitting and adjustment of cardiac device
    • V53.31 fitting and adjustment of cardiac pacemaker
    • V53.32 fitting and adjustment of automatic implantable cardiac defibrillator
    • V53.39 fitting and adjustment of other cardiac device

ICD-10 codes

  • Z45.0 adjustment and management of cardiac pacemaker
  • Z95.0 presence of cardiac pacemaker
  • Z95.8 presence of other cardiac vascular implants and grafts

References

General references used

  • 1. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Oct 15;128(16):e240-319 full-text, also published in J Am Coll Cardiol 2013 Oct 15;62(16):e147
  • 2. Epstein AE, DiMarco JP, Ellenbogen KA, et al; American College of Cardiology Foundation, American Heart Association Task Force on Practice Guidelines, Heart Rhythm Society. 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2013 Jan 22;127(3):e283-352 also published in J Am Coll Cardiol 2013 Jan 22;61(3):e6
  • 3. European Society of Cardiology (ESC), European Heart Rhythm Association (EHRA), Brignole M, Auricchio A, Baron-Esquivias G, et al. 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: the task force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Europace. 2013 Aug;15(8):1070-118, correction can be found in Europace 2013 Oct;15(10):1533
  • 4. Exner DV, Birnie DH, Moe G, et al. Canadian Cardiovascular Society guidelines on the use of cardiac resynchronization therapy: evidence and patient selection. Can J Cardiol. 2013 Feb;29(2):182-95
  • 5. Parkash R, Philippon F, Shanks M,et al. Canadian Cardiovascular Society guidelines on the use of cardiac resynchronization therapy: implementation. Can J Cardiol. 2013 Nov;29(11):1346-60
  • 6. European Heart Rhythm Association, European Society of Cardiology, Heart Rhythm Society, Heart Failure Society of America, American Society of Echocardiography, American Heart Association, European Association of Echocardiography, Heart Failure Association, Daubert JC, Saxon L, Adamson PB, et al. 2012 EHRA/HRS expert consensus statement on cardiac resynchronization therapy in heart failure: implant and follow-up recommendations and management. Heart Rhythm. 2012 Sep;9(9):1524-76, also published in Europace 2012 Sep;14(9):1236

Recommendation grading systems used

  • Scottish Intercollegiate Guidelines Network (SIGN) grading system
    • levels of evidence
      • Level 1++ - high-quality meta-analyses, systematic reviews of randomized controlled trials (RCTs) or RCTs with very low risk of bias
      • Level 1+ - well-conducted meta-analyses, systematic reviews, or RCTs with low risk of bias
      • Level 1- - meta-analyses, systematic reviews, or RCTs with high risk of bias
      • Level 2++
        • high-quality systematic reviews of case-control or cohort studies
        • high-quality case-control or cohort studies with very low risk of confounding or bias and high probability that relationship is causal
      • Level 2+ - well-conducted case-control or cohort studies with low risk of confounding or bias and moderate probability that relationship is causal
      • Level 2- - case-control or cohort studies with high risk of confounding or bias and significant risk that relationship not causal
      • Level 3 - nonanalytic studies (such as case reports, case series)
      • Level 4 - expert opinion
    • strength of recommendation
      • Strong (recommendations on interventions that should not be considered) - guideline development group confident that for vast majority of people intervention will do more harm than good
      • Conditional (recommendations on interventions that should be considered)
        • guideline development group confident intervention with do more good than harm for most patients
        • choice of intervention more likely to vary depending on person's values and preferences so healthcare professionals should spend more time discussing options with patients
      • Good Practice Point - recommended best practice based on clinical experience of guideline development group
    • Reference - SIGN national clinical guideline on management of chronic heart failure (SIGN 2016 Mar PDF)
  • American College of Cardiology Foundation/American Heart Association (ACCF/AHA) grading system for recommendations
    • classifications of recommendations
      • Class I - procedure or treatment should be performed or administered
      • Class IIa - reasonable to perform procedure or administer treatment, but additional studies with focused objectives needed
      • Class IIb - procedure or treatment may be considered; additional studies with broad objectives needed, additional registry data would be useful
      • Class III - procedure or treatment should not be performed or administered because it is not helpful or may be harmful
        • Class III ratings may be subclassified as Class III No Benefit or Class III Harm
    • levels of evidence
      • Level A - data derived from multiple randomized clinical trials or meta-analyses
      • Level B - data derived from single randomized trial or nonrandomized studies
      • Level C - only consensus opinions of experts, case studies, or standard of care
  • European Society of Cardiology (ESC) grading system for recommendations
    • classes of recommendations
      • Class I - evidence and/or general agreement that given treatment or procedure is beneficial, useful, and effective
      • Class II - conflicting evidence and/or divergence of opinion about usefulness/efficacy of given treatment or procedure
        • Class IIa - weight of evidence/opinion in favor of usefulness/efficacy
        • Class IIb - usefulness/efficacy less well established by evidence/opinion
      • Class III - evidence or general agreement that given treatment or procedure is not useful/effective, and in some cases may be harmful
    • levels of evidence
      • Level A - data derived from multiple randomized clinical trials or meta-analyses
      • Level B - data derived from single randomized trial or large nonrandomized studies
      • Level C - consensus of opinion of experts and/or small studies, retrospective studies, registries
  • Canadian Cardiovascular Society (CCS) grading system for recommendations
    • strength of recommendation
      • Strong
      • Conditional (weak)
    • quality of evidence
      • High - future research unlikely to change confidence in estimate of effect; multiple well-designed, well-conducted clinical trials
      • Moderate - further research likely to have important impact on confidence in estimate of effect and may change estimate; limited clinical trials, inconsistency of results, or study limitations
      • Low - further research very likely to have significant impact on estimate of effect and is likely to change estimate; small number of clinical studies or cohort observations
      • Very Low - estimate of effect is very uncertain; case studies
    • References

DynaMed editorial process

  • DynaMed topics are created and maintained by the DynaMed Editorial Team and Process.
  • All editorial team members and reviewers have declared that they have no financial or other competing interests related to this topic, unless otherwise indicated.
  • DynaMed provides Practice-Changing DynaMed Updates, with support from our partners, McMaster University and F1000.

Special acknowledgements

  • Eric Adler, MD (Associate Clinical Professor of Cardiology, University of California; California, United States)
  • Allen Shaughnessy, PharmD, M Med Ed, FCCP (Professor of Family Medicine and Director of Master Teacher Fellowship, Tufts University Family Medicine Residency; Cambridge Health Alliance; Massachusetts, United States)
  • Peter Oettgen MD, FACC, FAHA, FACP (Editor in Chief; Director of Preventive Cardiology, Beth Israel Deaconess Medical Center; Associate Professor of Medicine, Harvard Medical School, Massachusetts, United States)
  • Editorial Team role definitions
    Topic Editors define the scope and focus of each topic by formulating a set of clinical questions and suggesting important guidelines, clinical trials, and other data to be addressed within each topic. Topic Editors also serve as consultants for the internal DynaMed Plus Editorial Team during the writing and editing process, and review the final topic drafts prior to publication.
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How to cite

  • National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):
    • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 906121, Cardiac resynchronization therapy (CRT); [updated 2017 Mar 21, cited place cited date here]; [about 29 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=906121&site=dynamed-live&scope=site. Registration and login required.

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