This document addresses biventricular cardiac pacing to deliver cardiac resynchronization therapy (CRT) to alleviate the symptoms of moderate to severe congestive heart failure associated with left ventricular dyssynchrony.  It also addresses a hybrid device that combines CRT with an implantable cardioverter defibrillator (ICD).  In the combined device (CRT/ICD), the CRT component promotes coordinated contraction of both ventricles, while the ICD portion detects dangerous arrhythmias and shocks the heart back into a normal rhythm.

Medically Necessary:

FDA-approved biventricular pacemakers for cardiac resynchronization therapy (CRT) are considered medically necessary for individuals who meet all of the following criteria:

1. NYHA functional Class III or ambulatory Class IV symptoms, secondary to heart failure who remain symptomatic despite recommended, optimal medical therapy;* and
2. Who have cardiac dyssynchrony, (which is currently defined as a QRS duration greater than or equal to 120 ms); and
3. Left ventricular ejection fraction (LVEF) less than or equal to 35%; and
4. Are in sinus rhythm. 

FDA-approved biventricular pacemakers CRT are considered medically necessary for individuals who meet all of the following criteria:

1. NYHA functional Class II symptoms, secondary to heart failure who remain symptomatic despite recommended, optimal medical therapy;* and
2. Who have QRS duration greater than or equal to 130 ms; and
3. Left ventricular ejection fraction (LVEF) less than or equal to 30%; and
4. Are in sinus rhythm.

*See definition section for further information on New York Heart Association (NYHA) functional class. Optimal medical therapy may include use of the following medications either individually or in combination, unless contraindicated: angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, beta-blockers, digoxin, diuretics, and aldosterone antagonists, when appropriate.  Optimal medical therapy would include at least a 6 month trial period.

The use of an FDA-approved ICD, in combination with cardiac resynchronization therapy (CRT/ICD), is considered medically necessary when the criteria listed above for CRT therapy AND the criteria within SURG.00033  Implantable Cardioverter-Defibrillator (ICD) are met.

Investigational and Not Medically Necessary:

Biventricular pacemakers CRT, or combined biventricular pacemaker-defibrillator devices (CRT/ICD), are considered investigational and not medically necessary for all other indications.

There are a number of FDA approved biventricular pacemakers designed to provide cardiac resynchronization therapy (CRT).  Individuals meeting selection criteria for CRT therapy frequently are also considered candidates for an implantable cardiac defibrillator (ICD).  These persons may receive combined therapy with a combined CRT/ICD device.  

The InSync^® Biventricular Pacing System (Medtronic Inc., Minneapolis, MN) is an example of a biventricular pacemaker.  Its FDA labeling states that it is indicated for the treatment of individuals with New York Heart Association (NYHA) functional class III or IV heart failure, who remain symptomatic despite stable, optimal medical therapy, who additionally have a QRS duration of greater than or equal to 130 milliseconds, and a left ventricular ejection fraction (LVEF) of less than or equal to 35%.  The FDA approval was based on data collected in the Multi-Center InSync Randomized Clinical Evaluation (MIRACLE) trial.  In this trial, all subjects received a CRT device, but were then randomized to either active (device-on) or inactive (device-off) groups.  Overall, 68% of those in the active treatment group versus 35% of those in the inactive treatment group, demonstrated improvement in primary endpoints, including quality of life, 6-minute hall walk, and NYHA functional class.  The active treatment group also reported increases in a variety of cardiodynamic measures, including peak oxygen consumption, LV end diastolic dimension, and left ventricular ejection fraction (Abraham, 2002).

While the MIRACLE trial showed symptomatic improvement and improvement in cardiac function, the subsequent Cardiac Resynchronization – Heart Failure (CARE-HF) trial focused on the final health outcomes of morbidity and mortality (Cleland 2005).  A total of 813 subjects with left ventricular systolic dysfunction, cardiac dyssynchrony, and symptomatic heart failure were randomized to receive either CRT or standard medical care and followed for a mean of 29.4 months.  The primary endpoint, a composite of death from any cause or an unplanned hospitalization for a major cardiovascular event, was reached by 159 subjects in the CRT group, as compared with 224 in the medical therapy group (39% vs. 55%; hazard ratio 0.63; 95% CI, 0.51 to 0.77; p < 0.001).  The authors concluded that CRT substantially reduced the risk of complications and death among those subjects with moderate or severe heart failure, due to left ventricular systolic dysfunction and cardiac dyssynchrony.  Cleland and colleagues published another article in 2009 regarding the effects of CRT on long-term quality of life with data analysis taken from the CARE-HF trial.  Quality of life (QoL) was measured at baseline and 3 months using generic European QoL-5 Dimensions and disease-specific (Minnesota Living with Heart Failure) questionnaires and at 18 months and study-end using the latter instrument.  Median follow-up was 29.6 (interquartile range 23.6-34.6) months. The authors concluded that CRT improves long-term QoL and survival in individuals with moderate to severe heart failure.  The effects appear sustained, and therefore, the gain in quality of life with CRT should be even greater during longer term follow-up (Cleland, 2009).

The majority of studies of CRT have excluded individuals with atrial arrhythmias, which commonly occur in persons who would otherwise be considered candidates for CRT.  Therefore, there has been interest in evaluating CRT in this group.  For example, in the MUltisite STimulation In Cardiomyopathy (MUSTIC) study, 64 of the 131 enrolled subjects had atrial fibrillation (AF), in addition to heart failure and ventricular dyssynchrony (Cazeau, 2001).  All subjects received a biventricular implant, but during the initial three months of the trial, the participants were randomized to either active or inactive pacing, followed by cross over to the other arm for an additional three months (Linde, 2002).  Thirty-three of the participants with AF were followed up at 9 and 12 months to evaluate 6 minute walking distance, peak oxygen uptake and quality of life.  A total of 42 of the 67 subjects in sinus rhythm were similarly evaluated.  Trial subjects with AF showed similar improvements compared to those with normal sinus rhythm. 

Delnoy and colleagues (2007) reported on a prospective observational study enrolling 263 subjects undergoing CRT; 96 of these trial participants (37%) had coexisting AF and 167 (67%) were in normal sinus rhythm.  Clinical outcomes, hospitalization rates and left ventricular function were evaluated at 3 and 12 months.  All outcomes improved similarly in both groups.  The authors concluded that chronic AF should not be considered a contraindication for CRT.  

Upadhyay and colleagues (2008) conducted a meta-analysis of prospective cohort studies of CRT in subjects with AF and sinus rhythm.  A total of 5 studies enrolling 1,164 subjects met the study selection criteria.  The authors concluded that both groups benefited from CRT.  The NYHA classification improved similarly in both groups.  While those in sinus rhythm reported greater improvement in the 6 minute walk test, compared to those with AF, the AF group had greater improvement in the left ventricular ejection fraction. 

In 2008, the American College of Cardiology, American Heart Association and the Heart Rhythm Society (ACC/AHA/HRS) published updated guideline recommendations for Device-Based Therapy of Cardiac Rhythm Abnormalities (Epstein, 2008).  These guidelines noted that clinical trials of CRT have almost exclusively focused on individuals in sinus rhythm, but that "limited prospective experience" suggests that persons with AF can also benefit from CRT.  These guidelines state that CRT is "indicated" for individuals in sinus rhythm with chronic heart failure, (i.e., NYHA functional Class III or ambulatory Class IV symptoms) and dyssynchrony (Class I recommendation), while CRT is considered "reasonable" for the same persons with AF (Class IIa recommendation).  This Class IIa recommendation for AF was based on a single randomized controlled trial studying the effects of CRT in heart failure subjects with chronic AF, within which a 42% drop-out rate was observed, and an intention-to-treat analysis showed no significant difference between those receiving right ventricular and biventricular pacing. The authors caution that, "Further studies are required and that this treatment should not yet be recommended for this group of patients" (Leclercq, 2002).  The ACC/AHA/HRS guideline adds, "…Limited prospective experience among patients with permanent AF suggests that benefit may result from biventricular pacing when the QRS is prolonged, although it may be most evident in those patients in whom AV nodal ablation has been performed, such that right ventricular (RV) pacing is obligate" (Epstein, 2008).

The ACC/AHA/HRS guidelines also note that there is insufficient evidence regarding CRT in other individuals, including those with right bundle-branch block or other conduction abnormalities.  Despite these encouraging reports, the data regarding CRT in subjects with AF remains preliminary.  Only a small number of subjects have been enrolled in controlled trials.  Additional updated specialty society guidelines concur with the ACC/AHA/HRS recommendations described above (Jessup, 2009; Hunt, 2009).

Ongoing studies are examining the hypothesis that early use of CRT before the development of Class III symptoms may prevent or reverse remodeling, caused by prolonged ventricular conduction, thus preventing the progression of heart failure.  The REVERSE trial (REsynchronization reVErse Remodeling in Systolic left vEntricular dysfunction) enrolled 610 subjects with NYHA class I or II heart failure and a QRS interval greater than or equal to 120 ms and an LVEF  of less than 40% (Linde, 2008).  All trial participants received a CRT device with or without an ICD.  Trial participants were then randomized to active CRT (device-on) or control CRT (device-off) for 12 months.  The primary endpoint was a heart failure clinical composite score consisting of any incidence of death, hospitalization due to worsening heart failure or worsening symptoms.  Subjects were classified as "worsened" if any of the above criteria were met.  Subjects were classified as "improved" if there was an improvement in the NYHA class score or an improvement in symptoms.  The remaining subjects were classified as "unchanged."  This composite outcome was chosen because those who were mildly symptomatic were unlikely to have an event rate for any individual parameter that was sufficiently high to show a treatment effect from CRT, thus requiring a more sensitive composite outcome to detect any beneficial treatment effect. 

Of the 419 subjects assigned to the CRT-on group, 16% worsened compared to 21% of the 191 subjects assigned to the CRT-off group, a difference that was not statistically significant (p = 0.10).  Therefore, the trial results did not meet the primary outcome.  There was no significant difference in the number of hospitalizations between the two groups, but the time to first hospitalization was significantly delayed in the CRT-on group (hazard ratio 0.47, p = 0.03).  Left ventricular end-systolic volume index was evaluated as a measure of left ventricular remodeling.  Trial participants assigned to the CRT-on group experienced a greater improvement in this outcome.  These results suggest that while CRT can improve left ventricular remodeling, this improvement did not result in a significant improvement in clinical symptoms at one year.  Other studies have reported that left ventricular remodeling precedes symptomatic improvement in those with advanced heart failure (Yu 2005), so the authors suggest that the one year follow-up in the REVERSE study was not long enough to detect clinical improvement. 

Although the anticipated completion date for the REVERSE trial is November 2011, others have published information regarding the long-term effects of CRT in the European cohort enrolled in the REVERSE study.  A total of 262 recipients (with QRS greater than or equal to 120 ms and LV ejection fraction less than or equal to 40%) were randomly assigned to either CRT or CRT-ICD and were designated either to the active arm (CRT ON; n = 180) or the control arm (CRT OFF; n = 82) for 24 months.  Mean baseline LVEF was 28.0%.  All subjects were in sinus rhythm and receiving optimal medical therapy.  The primary study end point was the proportion worsened by the heart failure (HF) clinical composite response.  The main secondary study end point was left ventricular end-systolic volume index (LVESVi).  In the active treatment group, 19% worsened versus 34% in the control group (p = 0.01).  The LVESVi decreased by a mean of 27.5 +/- 31.8 ml/m(2) in the active treatment group versus 2.7 +/- 25.8 ml/m(2) in the control group (p < 0.0001).  Time to first hospital stay (for heart failure) or death (hazard ratio: 0.38; p = 0.003) was significantly delayed by CRT.  The authors concluded that after 24 months of CRT, and compared with those of control subjects, clinical outcomes and LV function were improved and LV dimensions were decreased in this population in NYHA functional classes I or II.  These observations suggest that CRT prevents the progression of disease in those with asymptomatic or mildly symptomatic LV dysfunction (Daubert, 2009). However, in 2010 another article was published regarding the 2-year outcomes of the REVERSE trial which showed no differences in VT/VF episodes or VT storm between groups. Specifically, in the CRT ON group, the estimated event rate was 18.7% at 2 years compared with 21.9% in the CRT OFF group (hazard ratio = 1.05, p = 0.84). However, among CRT ON subjects, those with reverse remodeling had a reduced incidence of VT/VF compared with those without remodeling (5.6% vs. 16.3%; hazard ratio = 0.31, p = 0.001).  These authors concluded that CRT for up to 2 years does not impact VT/VF in mild HF despite marked clinical and remodeling effects of pacing. This neutral effect may be due to competing antiarrhythmic effects of reverse remodeling and proarrhythmic effect of pacing (Gold, 2010).

Other trials also address this issue and are powered to measure morbidity and mortality rates.  The RAFT trial (Resynchronization/Defibrillation for Ambulatory Heart Failure Trial) is a multi-center, double-blind, randomized, controlled trial that was designed to determine if the addition of CRT to optimal pharmacological therapy and ICD is effective in reducing mortality and morbidity in individuals with mild to moderate heart failure symptoms (initially those with NYHA Cl II and III symptoms were included; this was changed to Cl II symptoms only in 2006 due to the observation that Cl III symptoms improve from CRT alone without ICD which was also in alignment with updated specialty society guideline recommendations; NLM Identifier:  NCT00251251).  Results of the RAFT trial were published in 2010 which investigated a total of 1798 subjects in 34 centers in multiple countries for a mean follow-up period of 40 + 20 months.  The primary outcome occurred in 297 of 894 subjects (33.2%) in the ICD–CRT group and 364 of 904 subjects (40.3%) in the ICD group (hazard ratio in the ICD–CRT group, 0.75; 95% confidence interval [CI], 0.64 to 0.87; P < 0.001). In the ICD–CRT group, 186 subjects died, as compared with 236 in the ICD group (hazard ratio, 0.75; 95% CI, 0.62 to 0.91; P = 0.003), and 174 were hospitalized for heart failure, as compared with 236 in the ICD group (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P < 0.001). However, at 30 days after device implantation, adverse events had occurred in 124 subjects in the ICD-CRT group, as compared with 58 in the ICD group (P < 0.001).  The authors concluded that among subjects with NYHA Class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure. This improvement was accompanied by more adverse events but is thought to provide convincing evidence in support of CRT for appropriately selected subjects with less severe heart failure disease (Cl II and III symptoms, left ventricular systolic dysfunction and a wide QRS complex).  These findings are consistent with the findings of two other major recent trials, the REVERSE and the MADIT-CRT (Tang, 2010; Moss, 2010).  

The MADIT-CRT was a randomized controlled trial of subjects with NYHA class I and II symptoms that was similarly designed to determine if CRT combined with an ICD would reduce the risk of mortality and heart failure (HF) events.  A total of 1820 subjects were enrolled (NLM Identifier: NCT00180271; 2008).  Results of the MADIT-CRT were reported in 2009 as follows:  during an average follow-up of 2.4 years, the primary end point occurred in 187 of 1089 subjects in the CRT-ICD group (17.2%) and 185 of 731 subjects in the ICD-only group (25.3%) (hazard ratio in the CRT-ICD group was 0.66; 95% confidence interval [CI], 0.52 to 0.84; P = 0.001). The benefit did not differ significantly between those subjects with ischemic cardiomyopathy and those with nonischemic cardiomyopathy.  The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events, a finding that was evident primarily in a prespecified subgroup with a QRS duration of 150 msec or more.  CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction.  There was no significant difference between the two groups in the overall risk of death, with a 3% annual mortality rate in each treatment group.  Serious adverse events were infrequent in the two groups.  The authors concluded that CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic subjects with a low ejection fraction and wide QRS complex (Moss, 2009).  

In 2010, Solomon reported further on the results of the MADIT-CRT trial using echocardiographic changes to evaluate whether the improvement in outcomes with CRT plus an ICD was associated with favorable alterations in cardiac size and function.  Echocardiographic studies were obtained at baseline and 12 months later in 1,372 of the MADIT-CRT subjects.  Changes in cardiac size and performance between treatment groups were compared and the relationship between these changes was assessed over the first year, as well as subsequent outcomes. Compared with the ICD-only group, the CRT-plus-ICD group had greater improvement in left ventricular end-diastolic volume index (-26.2 versus -7.4 mL/m[2]), left ventricular end-systolic volume index (-28.7 versus -9.1 mL/m[2]), left ventricular ejection fraction (11% versus 3%), left atrial volume index (-11.9 versus -4.7 mL/m[2]), and right ventricular fractional area change (8% versus 5%; P < 0.001 for all). Improvement in end-diastolic volume at 1 year was predictive of subsequent death or heart failure, with adjustment for baseline covariates and treatment group; each 10% decrease in end-diastolic volume was associated with a 40% reduction in risk (P < 0.001).  The authors of this analysis concluded that CRT resulted in significant improvement in cardiac size and performance compared with an ICD-only strategy in those subjects with mildly symptomatic heart failure.  Improvement in these measures accounted for the outcomes benefit (Solomon, 2010).

In May of 2002, the FDA approved the first hybrid device that combines CRT with an implantable cardioverter defibrillator (ICD), the CONTAK CD^® (Guidant Corp., St. Paul, MN).  The device is indicated for individuals at high-risk of sudden death due to ventricular arrhythmias and who have moderate to severe heart failure (NYHA Class III/IV), including left ventricular dysfunction (LVEF less than or equal to 35%) and QRS duration greater than or equal to 120 milliseconds, and who remain symptomatic despite stable, optimal heart failure drug therapy.  In July of 2002, the FDA approved a second device, the InSync^® ICD/CRT (Medtronic) with similar criteria including a QRS duration equal to or greater than 130 milliseconds.  In June of 2004, the FDA approved additional devices, the Epic^™ HF and Atlas^® + HF Dual Chamber Implantable Cardioverter Defibrillator Systems with cardiac resynchronization therapy (St Jude Medical^® Inc., Sunnyvale, CA) for ventricular antitachycardia pacing and ventricular defibrillation for automated treatment of life-threatening ventricular arrhythmias.  This device has similar criteria to the others, including a QRS duration equal to or greater than 150 milliseconds.

On September 16, 2010 the FDA approved expanded indications for three CRT devices (the Cognis^® CRT-D, Livian^™ CRT-D and Contak Renewal^® 3 RF HE CRT-D, Boston Scientific Corp., St. Paul, MN), based on the results of the MADIT-CRT trial as follows:
These CRT-D devices are indicated for individuals with heart failure who receive stable optimal pharmacologic therapy for heart failure and who meet any one of the following classifications:

1.  Moderate to severe heart failure (NYHA Class III-IV) with EF less than or equal to 35% and QRS duration greater than or equal to 120 ms; or
2. Left bundle branch block (LBBB) with QRS greater than or equal to 130 ms, EF less than or equal to 30%, and mild (NYHA Class II) ischemic or nonischemic heart failure or asymptomatic (NYHA Class I) ischemic heart failure (FDA, 2010).

In September of 2004, the FDA expanded the indications for the CONTAK^® RENEWAL^™ combined CRT/ICD devices to include ischemic and nonischemic heart failure subjects with LVEF less than or equal to 35% and a QRS duration greater than or equal to 120 milliseconds, who meet standards for New York Heart Association Class III/IV functional status and remain symptomatic despite optimal medical management.  The FDA decision (Sept. 2004) to expand the indications and usage labeling was based on data from the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial. 

The COMPANION trial was a multicenter, randomized, controlled trial to investigate whether prophylactic cardiac-resynchronization therapy with a biventricular pacemaker (CRT) or a pacemaker-defibrillator (CRT/ICD) would reduce the risk of death and hospitalization among individuals with advanced chronic heart failure and intra-ventricular conduction delays (Bristow, 2004).  A total of 1,520 subjects who had advanced heart failure (NYHA class III or IV), due to ischemic or non-ischemic cardiomyopathies and a QRS interval of at least 120 msec, were randomly assigned in a 1:2:2 ratio to receive optimal pharmacologic therapy, (e.g., diuretics, angiotensin-converting enzyme inhibitors, beta-blockers and spironolactone) alone or in combination with CRT or CRT/ICD.  The primary composite endpoint was the time-to-death from, or hospitalization for, any cause.  The results showed that compared to optimal pharmacological therapy alone, CRT with a pacemaker decreased the risk of the primary endpoint (hazard ratio, 0.81; p = 0.014), as did CRT/ICD (hazard ratio, 0.80; p = 0.01).  The risk of the combined endpoint of death from, or hospitalization for, heart failure was reduced by 34% in the pacemaker group (p < 0.002) and by 40% in the pacemaker-defibrillator group (p < 0.001 for the comparison with the pharmacological therapy group).  CRT therapy reduced the risk of the secondary endpoint of death from any cause by 24% (p = 0.059), and CRT/ICD therapy reduced the risk by 36% (p = 0.003).  The researchers concluded that in individuals with advanced heart failure and a prolonged QRS interval, CRT decreases the combined risk of death from any cause or of first hospitalization and, when combined with an implantable defibrillator, significantly reduces mortality.

Description of Relevant Disease

Approximately 5 million Americans are currently diagnosed with congestive heart failure, and more than 500,000 new cases are diagnosed each year. Individuals with CHF often have intra-ventricular conduction delays, evidenced by a wide QRS interval on electrocardiogram (EKG), which can worsen left ventricular systolic dysfunction through asynchronous ventricular contraction. There is inadequate filling of the left ventricle, as well as a backflow of blood into the left atrium, both resulting in decreased cardiac output and increased symptoms for the afflicted individual. Medical therapy for CHF includes a combination of diuretics, digoxin, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), beta-blockers and aldosterone antagonists. Some individuals may remain symptomatic, despite medical therapy. Current recommendations advise the optimization of pharmacological therapy before considering cardiac resynchronization therapy.

A biventricular pacemaker is designed to resynchronize the pumping action of the left ventricle. This type of pacing is called cardiac resynchronization therapy (CRT). Standard pacemakers pace the right side of the heart. In contrast, biventricular pacemakers pace both the right and left sides of the heart enabling the left ventricle to pump blood more efficiently. Biventricular pacemakers use three leads (one in the right atrium, one in each ventricle) and have been investigated as a technique to coordinate the contraction of the ventricles, thus, improving the individual's hemodynamic status.

Biventricular pacemakers are manufactured as "stand alone" devices (CRT) or with a built-in implantable cardioverter defibrillator (CRT/ICD). The combination devices provide treatment of ventricular dyssynchrony and ventricular tachyarrhythmias associated with sudden cardiac death, (e.g., ventricular tachycardia and ventricular fibrillation).

Arrhythmia: An irregular heartbeat which can be either an atrial or ventricular arrhythmia depending on which part of the heart the abnormal rhythm originates from.

Congestive heart failure (CHF) or heart failure: A condition in which the heart no longer adequately functions as a pump.  As blood flow out of the heart slows, blood returning to the heart through the veins backs up, causing congestion in the lungs and other organs.

Defibrillation:  A process in which an electronic device (a defibrillator) gives the heart an electric shock, helping reestablish normal contraction rhythms in a heart that is not properly beating.  This may be done using an external device or by a device implanted in the body, an implantable cardioverter defibrillator (ICD).

Left ventricular ejection fraction (LVEF):  The measurement of the heart's ability to pump blood through the body. Normal LVEF readings would be in the 58-70% range.

Myocardial infarction (MI):  The medical term for heart attack.  A heart attack occurs when the blood supply to part of the heart muscle (the myocardium) is severely reduced or blocked.

New York Heart Association (NYHA) Definitions:
The NYHA classification of heart failure is a 4-tier system that categorizes subjects based on subjective impression of the degree of functional compromise; the four NYHA functional classes are as follows:

• Class I - patients with cardiac disease but without resulting limitation of physical activity; ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain; symptoms only occur on severe exertion.
• Class II - patients with cardiac disease resulting in slight limitation of physical activity; they are comfortable at rest; ordinary physical activity (e.g., moderate physical exertion such as carrying shopping bags up several flights of stairs) results in fatigue, palpitation, dyspnea, or anginal pain.
• Class III - patients with cardiac disease resulting in marked limitation of physical activity; they are comfortable at rest; less than ordinary activity causes fatigue, palpitation, dyspnea or anginal pain.
• Class IV - patients with cardiac disease resulting in inability to carry on any physical activity without discomfort; symptoms of heart failure or the anginal syndrome may be present even at rest; if any physical activity is undertaken, discomfort is increased.

QRS complex:  Refers to a portion of a tracing within an electrocardiogram that represents the spread of the electrical impulse through the ventricles.  A prolonged QRS interval indicates a dyssynchrony of the right and left ventricle and is an important selection criterion for a biventricular pacemaker.   

Sudden cardiac death:  Death resulting from an abrupt loss of heart function (also known as cardiac arrest).

Ventricular tachyarrhythmias:  A medical term for a rapid heartbeat that may be regular or irregular arising from the ventricle or pumping chamber of the heart.  Two common tachyarrhythmias are ventricular tachycardia and ventricular fibrillation.

Ventricular fibrillation (Vfib or VF):  A condition in which the heart's electrical activity becomes disordered. When this happens, the heart's lower (pumping) chambers contract in a rapid, unsynchronized fashion (the ventricles "quiver" rather than beat) and the heart pumps little or no blood.

Ventricular tachycardia (Vtach or VT):  A fast regular heart rate that starts in the lower chambers (ventricles).  VT may result from serious heart disease and usually requires prompt treatment.

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. 

When services may be Medically Necessary when criteria are met:

When services are Investigational and Not Medically Necessary:
For the procedure codes listed above, when the criteria are not met, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Future ICD-10 coding (effective 10/01/2013)
A draft of ICD-10 Coding related to this document, as it might look today, is available for reference and comments at: Appendix 1: Future ICD-10 coding.

Peer Reviewed Publications:

1. Abraham WT, Fisher WG, Smith AL, et al. Cardiac resynchronization in chronic heart failure: The Multicenter InSync Randomized Clinical Evaluation (MIRACLE). N Engl J Med. 2002; 346(24):1845-1853.
2. Abraham WT, Young JB, Leon AR, et al. Effects of cardiac resynchronization on disease progression in patients with left ventricular systolic dysfunction and indication for an implantable cardioverter-defibrillator and mildly symptomatic heart failure.  Circ. 2004; 110:2864-2868.
3. Anand IS, Carson P, Galle E, et al. Cardiac resynchronization therapy reduces the risk of hospitalizations in patients with advanced heart failure: results from the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) trial. Circulation. 2009; 119(7):969-977.
4. Auricchio A, Metra M, Gasparini M, et al. Multicenter Longitudinal Observational Study (MILOS) Group. Long-term survival of patients with heart failure and ventricular conduction delay treated with cardiac resynchronization therapy. Am J Cardiol. 2007; 99(2):232-238.
5. Barsheshet A, Goldenberg I, Narins CR, et al.  Time dependence of life-threatening ventricular tachyarrhythmias after coronary revascularization in MADIT-CRT. Heart Rhythm. 2010; 7(10):1421-1427.
6. Beshai JF, Grimm RA, Nagueh SF, et al. Cardiac resynchronization therapy in heart failure with narrow QRS complexes.  N Engl J Med. 2007; 357(24):2461-2471.
7. Bleeker GB, Schalij MJ, Boersma E, et al. Relative merits of M-mode echocardiography and tissue Doppler imaging for prediction of response to cardiac resynchronization therapy in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2007; 99(1):68-74.
8. Bleeker GB, Holman ER, Steendijk P, et al. Cardiac resynchronization therapy in patients with a narrow QRS complex. J Am Coll Cardiol. 2006; 48(11):2243-2250.
9. Bradley DJ, Bradley EA, Baughman KL, et al. Cardiac resynchronization and death from progressive heart failure: a meta-analysis of randomized controlled trials. JAMA. 2003; 289(6):730-740.
10. Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004; 350(21):2140-2150.
11. Cazeau S, Leclercq C, Lavergne T et a.  Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay.  N Engl J Med 2001; 344:873-880.
12. Cleland JGF, Daubert JC, Erdmann E, et al. for the Cardiac Resynchronization – Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005; 352(15):1539-1549.
13. Cleland J, Freemantle N, Ghio S, et al.  Predicting the long-term effects of cardiac resynchronization therapy on mortality from baseline variables and the early response: a report from the CARE-HF (Cardiac  Resynchronization in Heart Failure) Trial.  J Am Coll Cardiol. 2008; 52(6):438-445.
14. Cleland JG, Calvert MJ, Verboven Y, Freemantle N. Effects of cardiac resynchronization therapy on long-term quality of life: an analysis from the Cardiac Resynchronization-Heart Failure (CARE-HF) study. Am Heart J. 2009; 157(3):457-466.
15. Daubert C, Gold MR, Abraham WT, et al. Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction: insights from the European cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. J Am Coll Cardiol. 2009; 54(20):1837-1846.
16. David Investigators. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the dual chamber and VVI implantable defibrillator (DAVID) trial. JAMA. 2002; 288(24):3115.
17. Delnoy PP, Ottervanger JP, Luttikhuis HO, et al. Comparison of usefulness of cardiac resynchronization therapy in patients with atrial fibrillation and heart failure versus patients with sinus rhythm and heart failure. Am J Cardiol. 2007; 99(9):1252-1257.
18. Doshi RN, Daoud EG, Fellows C, PAVE Study Group, et al. Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the PAVE study). J Cardiovasc Electrophysiol. 2005; 16(11):1160-1165.
19. Garrigue S, Bordachar P, Reuter S. et al. Comparison of permanent left ventricular and biventricular pacing in patients with heart failure and chronic atrial fibrillation: prospective haemodynamic study. Heart. 2002; 87(6):529-534.
20. Gasparini M, Auricchio A, Regoli F, et al. Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation. J Am Coll Cardiol. 2006; 48(4):734-743.
21. Gold MR, Linde C, Abraham WT, et al. The impact of cardiac resynchronization therapy on the incidence of ventricular arrhythmias in mild heart failure. Heart Rhythm. 2010 Dec 22. [Epub ahead of print].
22. Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med. 2004; 350(21):2151-2158.
23. Landolina M, Lunati M, Gasparini M, et al. Comparison of the effects of cardiac resynchronization therapy in patients with class II versus class III and IV heart failure (from the InSync ICD Italian Registry). Am J Cardiol. 2007; 100(6):1007-1012.
24. Leclercq C, Walker S, Linde C, et al. Comparative effects of permanent biventricular and right-univentricular pacing in heart failure patients with chronic atrial fibrillation. Eur Heart J. 2002; 23:1780-1787.
25. Leon AR, Greenberg JM, Kanuru N, et al. Cardiac resynchronization in patients with congestive heart failure and chronic atrial fibrillation: effect of upgrading to biventricular pacing after chronic right ventricular pacing.  J Am Coll Cardiol. 2002; 39:1258-1263.
26. Linde C, Abraham WT, Gold MR et al.  Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms.  J Am Coll Cardiol. 2008; 52(23):1834-1843.
27. Linde C, Braunschweig F, Gadler F, et al. Long-term improvements in quality of life by biventricular pacing in patients with chronic heart failure; results from the Multisite Stimulation in cardiomyopathy (MUSTIC) study (MUSTIC). Am J Cardiol. 2003; 91(9):1090-1095.
28. Lindenfeld J, Feldman AM, Saxon L, et al. Effects of cardiac resynchronization therapy with or without a defibrillator on survival and hospitalizations in patients with New York Heart Association class IV heart failure. Circulation. 2007; 115(2):204-212.
29. McAlister FA, Ezekowitz JA, Wiebe N, et al. Systematic review:  Cardiac resynchronization in patients with symptomatic heart failure.  Ann Intern Med. 2004; 141:381-390.
30. Molhoek SG, Bax JJ, Bleeker GB, et al. Long-term follow-up of cardiac resynchronization therapy in patients with end-stage heart failure. J Cardiovasc Electrophysiol. 2005; 16(7):701-707.
31. Molhoek SG, Bax JJ, Bleeker GB, et al. Comparison of response to cardiac resynchronization therapy in patients with sinus rhythm versus chronic atrial fibrillation. Am J Cardiol. 2004; 94(12):1506-1509.
32. Moss AJ.  Preventing heart failure and improving survival.  N Engl J Med. 2010; 363(25):2456-2457.
33. Moss AJ, Hall WJ, Cannom DS, et al. Cardiac resynchronization therapy for the prevention of heart failure events. N Engl J Med. 2009; 361(14):1329-1338. 
34. Saxon LA, Boehmer JP, Hummel J, et al. The VIGOR CHF and VENTAK CHF investigators. Biventricular pacing in patients with congestive heart failure; two prospective randomized trials. Am J Cardiol. 1999; 83(5B):120D-123D.
35. Solomon SD, Foster E, Bourgoun M, et al.  Effect of cardiac resynchronization therapy on reverse remodeling and relation to outcome: multicenter automatic defibrillator implantation trial: cardiac resynchronization therapy.  Circ. 2010; 122(10):985-992. 
36. St John Sutton M, Ghio S, Plappert T, et al.  Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association class I/II heart failure.  Circ. 2009; 120(19):1858-1865.
37. St. John Sutton MG, Plappert T, Abraham WT, et al. Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure.  Circ. 2003; 107:1985-1900.
38. Sutton MG, Plappert T, Hilpisch KE, et al. Sustained reverse left ventricular structural remodeling with cardiac resynchronization at one year is a function of etiology: quantitative Doppler echocardiographic evidence from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE). Circ. 2006; 113(2):266-272.
39. Sweeney MO, Ellenbogen KA, Casavant D, et al. Multicenter prospective randomized safety and efficacy study of a new atrial-based managed ventricular pacing mode (MVP) in dual chamber ICDs. J Cardiovasc Electrophysiol. 2005; 16(8):811-817.
40. Tang ASL, Wells GA, Talajic M, et al.  Cardiac resynchronization therapy for mild to moderate heart failure.  N Engl J Med. 2010; 363(25):2385-2395.
41. Upadhyay GA, Choudhry NK, Auricchio A et al.  Cardiac resynchronization in patients with atrial fibrillation: a meta-analysis of prospective cohort studies.  J Am Coll Cardiol. 2008; 52:1239-1246.
42. Wikstrom G, Blomström-Lundqvist C, Andren B, et al. The effects of etiology on outcome in patients treated with cardiac resynchronization therapy in the CARE-HF trial. Eur Heart J. 2009; 30(7):782-788.
43. Yancy CW, Fonarow GC, Albert NM, et al. Influence of patient age and sex on delivery of guideline-recommended heart failure care in the outpatient cardiology practice setting: findings from IMPROVE HF. Am Heart J. 2009; 157(4):754-762.
44. Young JB, Abraham WT, Smith AL, et al. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial. JAMA. 2003; 289(20):2685-2694.
45. Yu CM, Abraham WT, Bax J, et al. Predictors of response to cardiac resynchronization therapy (PROSPECT)--study design. Am Heart J. 2005; 149(4):600-605.

Government Agency, Medical Society, and other Authoritative Publications:

1. Blue Cross Blue Shield Association. Cardiac Resynchronization Therapy for Mild Congestive Heart Failure. TEC Assessment, October 1, 2009.
2. Boston Scientific Corporation, University of Rochester. MADIT-CRT Automatic defibrillator implantation with cardiac resynchronization therapy. NLM Identifier: NCT00180271. Last updated on July 12, 2010. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00180271?term=MADIT+CRT&rank=1.  Accessed on January 3, 2011.
3. Centers for Medicare and Medicaid Services. National Coverage Determination for Cardiac Pacemakers. NCD#20.8. Effective April 30, 2004. Available at: https://www.cms.hhs.gov/mcd/viewncd.asp?ncd_id=20.8&ncd_version=2&basket=ncd%3A20%2E8%3A2%3ACardiac+Pacemakers.  Accessed on January 3, 2011.
4. Dickstein K, Vardas PE, Auricchio A, et al.  2010 Focused Update of ESC Guidelines on Device Therapy in Heart Failure:  An update of the 2008 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure and the 2007 ESC Guidelines for Cardiac and Resynchronization Therapy developed with the special contribution of the Heart Failure Association and the European Heart Rhythm Association.  Published online in advance.  August 27, 2010.  Available at:  http://eurheartj.oxfordjournals.org/content/early/2010/08/27/eurheartj.ehq337.full.pdf.  Accessed on January 14, 2011.
5. Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) Developed in Collaboration With the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008; 51:1-62.  Available at: http://content.onlinejacc.org/cgi/reprint/51/21/e1.pdf.  Accessed on January 3, 2011.
6. Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, et al. American College of Cardiology; American Heart Association Task Force; European Society of Cardiology Committee for Practice Guidelines; European Heart Rhythm Association; Heart Rhythm Society. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 guidelines for the management of patients with atrial fibrillation) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Europace. 2006; 8(9):651-745.  Available at: http://circ.ahajournals.org/cgi/reprint/114/7/e257.  Accessed on January 3, 2011.
7. Gorcsan J 3rd, Abraham T, Agler DA, et al. American Society of Echocardiography Dyssynchrony Writing Group. Echocardiography for cardiac resynchronization therapy: recommendations for performance and reporting--a report from the American Society of Echocardiography Dyssynchrony Writing Group endorsed by the Heart Rhythm Society. J Am Soc Echocardiogr. 2008; 21(3):191-213.
8. Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2009; 53:e1–90.  Available at:  http://content.onlinejacc.org/cgi/reprint/53/15/e1.pdf.  Accessed on January 3, 2011.
9. Jessup M, Abraham WT, Casey DE, et al. writing on behalf of the 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult Writing Committee. 2009 focused update: ACCF/AHA guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2009; 53:1343– 1382. Available at:  http://content.onlinejacc.org/cgi/reprint/53/15/1343.pdf.  Accessed on January 3, 2011.
10. McAlister FA, Ezekowitz J, Dryden DM, Hooton N, Vandermeer B, Friesen C, Spooner C, Rowe BH. Cardiac Resynchronization Therapy and Implantable Cardiac Defibrillators in Left Ventricular Systolic Dysfunction. Evidence Report/Technology Assessment No. 152 (Prepared by the University of Alberta Evidence-based Practice Center under Contract No. 290-02-0023). AHRQ Publication No. 07-E009. Rockville, MD: Agency for Healthcare Research and Quality. June 2007. Available at:  http://www.ahrq.gov/downloads/pub/evidence/pdf/defib/defib.pdf.  Accessed on January 3, 2011.
11. McAlister F, Ezekowitz J, Wiebe N, Rowe B, Spooner C, Crumley E, Hartling L, Kaul P, Nichol G, Klassen T. Cardiac Resynchronization Therapy for Congestive Heart Failure. Evidence Report/Technology Assessment No. 106. (Prepared by the University of Alberta Evidence-based Practice Center under Contract No. 290-02-0023.) AHRQ Publication No. 05-E001-2. Rockville MD: Agency for Healthcare Research and Quality. November 2004.  Available at:  http://www.ahrq.gov/downloads/pub/evidence/pdf/resynchf/resynchf.pdf.  Accessed on January 3, 2011.
12. Medtronic Cardiac Rhythm Disease Management.  Medtronic, Inc.  REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction (REVERSE).  NLM Identifier: NCT00271154.  Last updated on September 28, 2010.  Available at: http://clinicaltrials.gov/ct2/show/NCT00271154?term=NCT00271154&rank=1.  Accessed on January 3, 2011.
13. National Institute for Health and Clinical Excellence (NICE). Technology appraisal guidance TA120. Cardiac resynchronization therapy for the treatment of heart failure. May 23, 2007.  Updated:  July 2010. Available at: http://www.nice.org.uk/nicemedia/pdf/TA120guidance.pdf.  Accessed on January 3, 2011.
14. Strickberger SA, Conti J, Daoud EG, et al. Council on Clinical Cardiology Subcommittee on Electrocardiography and Arrhythmias and the Quality of Care and Outcomes Research Interdisciplinary Working Group; Heart Rhythm Society. Patient selection for cardiac resynchronization therapy: from the Council on Clinical Cardiology Subcommittee on Electrocardiography and Arrhythmias and the Quality of Care and Outcomes Research Interdisciplinary Working Group, in collaboration with the Heart Rhythm Society. Circulation. 2005; 111(16):2146-2150.
15. University of Ottowa Heart Institute, Canadian Institutes of Health Research (CIHR), Medtronic, Inc. Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT).  NLM Identifier: NCT00251251. Last updated on April 27, 2009  Available at: http://www.clinicaltrials.gov/ct2/show/NCT00251251?term=Resynchronization%2Fdefibrillation&rank=1  Accessed on January 3, 2011.
16. U.S. Food and Drug Administration (FDA). Center for Devices and Radiological Health. Summary of Safety and Effectiveness for Medtronic InSync^® Biventricular Pacing System. P010015. Original PMA date: August 28, 2001. Available at:  http://www.accessdata.fda.gov/cdrh_docs/pdf/P010015A.pdf.  Accessed on January 3, 2011.
17. U.S. Food and Drug Administration (FDA). Center for Devices and Radiological Health. Premarket Approval (PMA) Database. St. Jude Medical^® Frontier and Frontier II biventricular pacing systems. PMA number P030035. Original PMA date:  May 13, 2004.  Available at URL address: http://www.accessdata.fda.gov/cdrh_docs/pdf3/P030035A.pdf.  Accessed on January 3, 2011.
18. U.S. Food and Drug Administration (FDA). Center for Devices and Radiological Health. Update of FDA Preliminary Public Health Notification: Guidant VENTAK PRIZM^® 2 DR and CONTAK RENEWAL^® Implantable Cardioverter Defibrillators.  October 13, 2005.  Last updated:  November 18, 2010.  Available at: http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/ucm062113.htm. Accessed on January 3, 2011.
19. U.S. Food and Drug Administration (FDA). Center for Devices and Radiological Health. St. Jude Medical^® Epic^™ HF dual chamber implantable cardioverter defibrillator systems with cardiac resynchronization therapy. P030054. June 30, 2004. Available at:    http://www.accessdata.fda.gov/cdrh_docs/pdf3/P030054A.pdf.  Accessed on January 3, 2011.
20. U.S. Food and Drug Administration (FDA).  Center for Devices and Radiological Health.  Premarket Approval (PMA) Database.  Ela Medical, Inc., (Plymouth, MN) Ovatio CRT-D System.  PMA number P060027.  May 15, 2008.  Available at:   http://www.accessdata.fda.gov/cdrh_docs/pdf6/P060027a.pdf.  Accessed on January 3, 2011.
21. U.S. Food and Drug Administration (FDA).  Center for Devices and Radiological Health.  Premarket Approvals (PMA).  Available at:  http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances
    /PMAApprovals/ucm230212.htm.  Accessed on January 21, 2011.U.S. Food and Drug Administration (FDA).  Center for Devices and Radiological Health.  Boston Scientific Corporation. Cognis CRT-D, Livian CRT-D and Contak Renewal 3 RF HE CRT-D. P010012/S230. September 16, 2010.  Available at:  http://www.accessdata.fda.gov/cdrh_docs/pdf/P010012S230a.pdf.  Accessed on January 21, 2011.
22. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death). Circulation. 2006; 114(10):1088-1132. Available at: http://circ.ahajournals.org/cgi/reprint/114/10/e385. Accessed on January 3, 2011.

1. Consumer information from the U.S. Food and Drug Administration (FDA).  Available at: http://www.fda.gov/hearthealth.  Accessed on January 3, 2011.
2. Heart failure. Available at: http://www.heartfailure.org/.  Accessed on January 3, 2011.
3. Heart Rhythm Society- Resynchronization Therapy for Heart Failure.  Available at:  http://www.hrsonline.org/Policy/ClinicalGuidelines/upload/resynch_therapy_HF.pdf.  Accessed on January 3, 2011.
4. National Heart, Lung and Blood Institute available at:  Available at: http://www.nhlbi.nih.gov/health/dci/Diseases/Hf/HF_WhatIs.html.  Accessed on January 3, 2011.

Atlas^® + HF
Biventricular Pacemaker
CONTAK^®RENEWAL^™
Epic^™ HF
InSync^® Biventricular Pacing System
InSync^® ICD Dual Chamber ICD with CRT 

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.