Download Biventricular Pacemakers (Cardiac

MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
Original Issue Date (Created):
7/1/2002
Most Recent Review Date (Revised):
11/29/2016
Effective Date:
4/1/2017
POLICY
RATIONALE
DISCLAIMER
POLICY HISTORY
PRODUCT VARIATIONS
DEFINITIONS
CODING INFORMATION
DESCRIPTION/BACKGROUND
BENEFIT VARIATIONS
REFERENCES
I. POLICY
Biventricular pacemakers with or without an accompanying implantable cardiac defibrillator
(i.e., a combined biventricular pacemaker plus an implantable cardiac defibrillator)) may be
considered medically necessary as a treatment of heart failure in patients who meet all of the
following criteria:
New York Heart Association (NYHA) Class III or IV;
 Left ventricular ejection fraction  (less than or equal to) 35%;
 Sinus rhythm
 Patients treated with guideline-directed medical therapy (see Policy Guidelines section)
 Either left bundle branch block or QRS duration ≥120 ms*
New York Heart Association class II
 Left ventricular ejection fraction ≤30%
 Sinus rhythm
 Patients treated with a guideline-directed medical therapy (see Policy Guidelines section)
 Either left bundle branch block or QRS duration ≥150 ms*
* U.S. Food and Drug Administration (FDA) ‒labeled indications for QRS duration vary by
device. For some devices, FDA approval is based on QRS duration of ≥130 (eg, InSync®
device), while for others, it is based on QRS duration ≥120 ms (eg, CONTAK CD® CRT-D
System). These differences in QRS duration arise from differences in the eligibility criteria in
the trials on which the FDA approval is based.
A ventricular pacemaker or biventricular pacemakers with or without an accompanying
implantable cardiac defibrillator (ie, a combined biventricular pacemaker/implantable cardiac
defibrillator)) may be considered medically necessary as an alternative to a right ventricular
pacemaker in patients who meet all of the following criteria:
Page 1
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007




NYHA class I, II, III, or IV heart failure;
Left ventricular ejection fraction ≤50%;
The presence of atrioventricular (AV) block with requirement for a high percentage of
ventricular pacing (see Policy Guidelines section);
Patients treated with guideline-directed medical therapy (see Policy Guidelines section)
Biventricular pacemakers with or without an accompanying implantable cardiac defibrillator
as an alternative to a right ventricular pacemaker are considered investigational for patients
who do not meet the above criteria. There is insufficient evidence to support a conclusion
concerning the health outcomes or benefits associated with this procedure.
Biventricular pacemakers, with or without an accompanying implantable cardiac defibrillator
(i.e., a combined biventricular pacemaker/ICD), are considered investigational as a treatment
for heart failure in patients with atrial fibrillation. There is insufficient evidence to support a
conclusion concerning the health outcomes or benefits associated with this procedure.
The use of biventricular pacemakers (cardiac resynchronization therapy) for treatment of heart
failure in situations other than those described in the policy section are considered
investigational. There is insufficient evidence to support a conclusion concerning the health
outcomes or benefits associated with this procedure.
An intrathoracic fluid-monitoring sensor is considered investigational as a component of a
biventricular pacemaker, as there is insufficient evidence to support a conclusion concerning the
health outcomes or benefits associated with this procedure.
Triple-site (triventricular) CRT, using an additional pacing lead, is considered investigational.
There is insufficient evidence to support a conclusion concerning the health outcomes or
benefits associated with this procedure.
Policy Guidelines
AV block with a requirement for a high percentage of ventricular pacing is considered to be
present when there is either:


3rd degree AV block; or
2nd degree AV block or a PR interval of 300 ms or more when paced at 100 beats per
minute.
Page 2
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
Guideline-directed medical therapy for heart failure is outlined in 2013 American College of
Cardiology Foundation/American Heart Association guidelines for the management of heart
failure.1 [Website]:
http://www.guideline.gov/content.aspx?id=47343&search=american+college+of+cardiology+fo
undation%2famerican+heart+association+guidelines
Cross-references:
MP-1.081 Cardioverter-Defibrillators (Implantable and External)
MP-2.051 Cardiac Hemodynamic Monitoring for the Management of Heart Failure in the
Outpatient Setting
II. PRODUCT VARIATIONS
TOP
This policy is applicable to all programs and products administered by Capital BlueCross unless
otherwise indicated below.
BlueJourney HMO*
BlueJourney PPO*
FEP PPO**
* Refer to Centers for Medicare and Medicaid (CMS) National Coverage Determination
(NCD) 20.8, Cardiac Pacemakers and 20.8.3 Cardiac Pacemakers: Single Chamber and Dual
Chamber Permanent Cardiac Pacemakers for additional pacemaker indications.
* Refer to Novitas Solutions Local Coverage Article (LCA) A54982 Single Chamber and Dual
Chamber Permanent Cardiac Pacemakers – Coding and Billing.
** Refer to the FEP Medical Policy Manual MP-2.02.10 Biventricular Pacemakers for Treatment
of Heart Failure. The FEP Medical Policy manual can be found at: www.fepblue.org
III. DESCRIPTION/BACKGROUND
TOP
Cardiac resynchronization therapy (CRT), which consists of synchronized pacing of the left and
right ventricles, is intended to treat patients with heart failure and dyssynchronous ventricular
contractions. Treatment involves placement of a device that paces both ventricles and
coordinates ventricular pacing to maximize cardiac pumping function and left ventricular
ejection fraction.
Page 3
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
It is estimated that 20% to 30% of patients with heart failure have intraventricular conduction
disorders, resulting in a contraction pattern that is not coordinated and a wide QRS interval on
the electrocardiogram. This abnormality appears to be associated with increased morbidity and
mortality. Biventricular pacemakers using 3 leads (1 in the right atrium, 1 in each ventricle), also
known as CRT, have been investigated as a technique to coordinate the contraction of the
ventricles, thus improving patients’ hemodynamic status. Several types of CRT devices are
available, including those that incorporate biventricular pacing into automatic implantable
cardiac defibrillators (ICDs), stand-alone biventricular pacemakers, and biventricular
pacemakers that incorporate fluid monitoring via bioimpedance.
Originally developed CRT devices typically used 2 ventricular leads for biventricular pacing.
Devices and implantation techniques have been developed to allow for multisite pacing, with the
goal of improving CRT response. This may be accomplished in 1 of 2 ways: through the use of
multiple leads within the coronary sinus (triventricular pacing) or through the use of multipolar
left ventricular pacing leads, which can deliver pacing stimuli at multiple sites.
Regulatory Status
There are numerous cardiac resynchronization therapy (CRT) devices, combined implantable
cardiac defibrillator (ICD) plus CRT devices (CRT-D), and combined CRT plus fluid monitoring
devices. Some devices are discussed here. For example, in 2001, the InSync® Biventricular
Pacing System (Medtronic), a stand-alone biventricular pacemaker, was approved by the U.S.
Food and Drug Administration (FDA) through the premarket approval process for the treatment
of patients with New York Heart Association (NYHA) class III or IV heart failure, on a stable
pharmacologic regimen, who also have a QRS duration of 130 ms or longer and a left ventricular
ejection fraction (LVEF) of 35% or less. Devices by Guidant (CONTAK CD® CRT-D System)
and Medtronic (InSync® ICD Model 7272) have been approved by FDA through the premarket
approval process for combined cardiac resynchronization therapy defibrillators for patients at
high risk of sudden cardiac death due to ventricular arrhythmias and who have NYHA class III
or IV heart failure with LVEF of 35% or less, QRS duration 130 ms or longer (≥120 ms for the
Guidant device), and remain symptomatic despite a stable, optimal heart failure drug therapy. In
2006, Biotronik Inc. received premarket approval from FDA for its combined ICD-CRT device
with ventricular pacing leads (Tupos LV/ATx CRT-D/Kronos LV-T CRT-D systems1); in 2013,
the company received FDA approval for updated ICD-CRT devices (Ilesto/Iforia series).2
In September 2010, FDA expanded indications for some CRT devices to include patients with
class I and II heart failure. Based on data from the MADIT-CRT study, indications for 3 Guidant
(Boston Scientific) CRT-ICDs (Cognis®, Livian®, and Contak Renewal devices) were expanded
to include patients with heart failure who receive stable optimal pharmacologic therapy for heart
failure and who meet any one of the following classifications3:

Moderate-to-severe heart failure (NYHA class III-IV) with ejection fraction less than
35% and QRS duration greater than 120 ms.
Page 4
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007

Left bundle branch block with QRS greater than or equal to 130 ms, ejection fraction
less than 30%, and mild (NYHA class II) ischemic or nonischemic heart failure or
asymptomatic (NYHA class I) ischemic heart failure.
In April 2014, FDA further expanded indications for multiple Medtronic CRT devices to include
patients with NYHA functional class I, II, or III heart failure, who have LVEF of 50% or less on
stable, optimal heart failure medical therapy, if indicated, and have atrioventricular (AV) block
that is expected to require a high percentage of ventricular pacing that cannot be managed with
algorithms to minimize right ventricular pacing. The expanded indication was based on data
from the BLOCK-HF study, a Medtronic-sponsored randomized controlled trial that evaluated
use of CRT in patients with NYHA class I, II, or III heart failure, LVEF of 50% or less, and AV
block.
Several CRT devices incorporate a fourth lead, providing quadripolar pacing. The Medtronic
Viva™ Quad XT and the Viva Quad S incorporate a fourth lead, the Medtronic Attain
Performa® left ventricular lead, which received clearance for marketing from FDA in August
2014. The Dynagen™ X4 and Inogen™ X4 devices (Boston Scientific, Marlborough, MA) also
incorporate a fourth lead. Other CRT devices with quadripolar leads have been approved for use
outside of the United States (eg, St. Jude Quartet™ left ventricular lead).
Multiple devices manufactured by Medtronic combine a CRT with the OptiVol™ monitoring
system. For example, in 2005, the InSync Sentry® system was approved by FDA through the
supplemental premarket approval process. This combined biventricular pacemaker plus ICD is
also equipped to monitor intrathoracic fluid levels using bioimpedance technology, referred to as
OptiVol™ Fluid Status Monitoring. Bioimpedance measures, defined as the electrical resistance
of tissue to flow of current, are performed many times a day using a vector from the right
ventricular coil on the lead in the right side of the heart to the implanted pacemaker devices;
changes in bioimpedance reflect intrathoracic fluid status and are evaluated using a computer
algorithm. For example, changes in a patient’s daily average of intrathoracic bioimpedance can
be monitored; differences in the daily average are compared with a baseline and reported as the
OptiVol Fluid Index. It has been proposed that these data may be used as an early warning
system of cardiac decompensation or may provide feedback that enables a physician to tailor
medical therapy. Evidence review 2.02.24 addresses the use of external bioimpedance devices as
stand-alone devices to noninvasively assess cardiac output.
FDA product code: NIK.
IV. RATIONALE
TOP
This policy is updated periodically with literature review of the MEDLINE database. The most
recent update covers the period through March 24, 2016.
Page 5
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
Cardiac Resynchronization Therapy for Heart Failure
Advanced Heart Failure (New York Heart Association Class III/IV)
Use of biventricular pacemakers with or without accompanying implantable cardiac defibrillator
(ICD) for select patients with advanced heart failure is supported by a large body of clinical trial
evidence. For patients with the following characteristics, this treatment receives a class I
recommendation in the 2013 American College of Cardiology (ACC) and American Heart
Association (AHA) guidelines for the diagnosis and management of patients with heart failure,4
supported by level A evidence:





Left ventricular ejection fraction of 35% or less
Sinus rhythm
New York Heart Association (NYHA) functional class III or IV, despite optimal
medical therapy
Cardiac dyssynchrony as defined as a QRS greater than 120 ms
No contraindications for biventricular pacing.
The 2013 ACC/AHA guideline is accompanied by a review of the evidence, which states that
more than 4000 patients have been evaluated in randomized controlled trials (RCTs) and that
these trials have established that cardiac resynchronization therapy (CRT) in this patient
population improves functional status and exercise capacity.
A 2009 TEC Assessment of CRT for mild heart failure summarized 5 larger CRT trials for
advanced heart failure, showing that CRT improved quality of life (QOL) and functional status
for patients with class III and class IV heart failure.5 Four of the 5 trials reported improvements
in functional status for the CRT group. Similarly, 4 of the trials reported QOL measures, with all
4 showing significant improvements for the CRT group. Hospitalizations were reduced in 2 of
the 4 trials, with an additional 2 trials reporting no difference in hospitalizations. The
Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION)
trial, which had the highest enrollment and the longest follow-up of these trials, reported a
significant improvement in mortality.6 The other trials reported lower mortality for the CRT
group, which was not statistically significant.
A systematic review of 9 RCTs of CRT in class III or IV heart failure was published in 2004.7
This quantitative analysis drew the following conclusions: (1) left ventricular ejection fraction
(LVEF) improved by 3.5%; (2) QOL improved, with weighted mean difference on the
Minnesota Living with Heart Failure Questionnaire (MLHFQ) score of 7.6 points (0-100 scale);
and (3) functional capacity improved and all-cause mortality was reduced by 21%. This analysis
also found some evidence that cardiac morphology may be improved, suggesting that CRT may
prevent, delay, or even reverse the changes in morphology resulting from chronic heart failure
(reverse remodeling).
Page 6
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
Mild Heart Failure (NYHA Class I/II)
Evaluation of CRT for mild heart failure was originally based on a 2009 TEC Assessment.5
There is less evidence on treatment of mild heart failure compared with that for advanced heart
failure, but clinical trial evidence is available. At least 4 RCTs enrolling over 3000 patients, with
follow-up ranging from 6 months to 2.4 years, have been published to date. A summary of the
major RCTs for mild heart failure is provided.
MADIT-CRT Trial
The largest trial published to date was the single-blind Multicenter Automatic Implantation
Trial–Cardiac Resynchronization (MADIT-CRT) trial, which randomized 1820 patients with
NYHA class I or I heart failure to an ICD alone or an ICD-CRT device.8 The MADIT-CRT trial
reported a reduction for the ICD-CRT group on the primary outcome (ie, death or acute heart
failure exacerbation). The primary end point was reached by 17.2% of patients in the ICD-CRT
group compared with 25.3% of patients in the ICD-alone group. The first component of the
composite outcome (acute heart failure events) occurred in 22.8% of patients in the ICD-alone
group compared with 13.9% of patients in the ICD-CRT group (relative risk reduction, 39%;
absolute risk reduction, 8.9%; number needed to treat, 11.2). This difference in acute heart
failure events accounted entirely for the difference on the primary composite outcome. The death
rate was similar between groups.
A follow-up from the MADIT-CRT trial, published in 2011, analyzed the reduction in recurrent
heart failure events.9 This analysis supplemented the original MADIT-CRT outcome of time to
first heart failure event, by comparing total heart failure events during an average follow-up of
2.6 years. Over this time period, there was a 38% relative reduction in heart failure events in the
CRT group (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.45 to 0.85; p=0.003). On
subgroup analysis, the benefit was evident in patients with left bundle branch block (LBBB;
HR=0.50; 95% CI, 0.33 to 0.76; p=0.001) but not in patients without LBBB (HR=0.99; 95% CI,
0.58 to 1.69; p=0.96).
In 2014, Goldenberg et al analyzed mortality in the MADIT-CRT trial subjects with follow-up
through 7 years, stratified by the presence or absence of LBBB.10 Follow-up was available for a
median 5.6 years among all 1691 surviving patients enrolled in the trial, and beyond that for 854
subjects enrolled in posttrial registries. Seventy-three percent and 75% of the ICD-only and ICDCRT groups, respectively, had LBBB; 69% of each group had QRS duration of a least 150 ms.
At 7-year follow-up, the cumulative rate of death from any cause among patients with LBBB
was 29% in the ICD-only group compared with 18% in the ICD-CRT group (unadjusted log-rank
test, p=0.002; adjusted HR in the ICD-CRT group, 0.59; 95% CI, 0.43 to 0.80; p<0.001). The
benefit associated with ICD-CRT was consistent in subgroup analysis among patients with
prolonged QRS duration (≥150 ms) and shorter QRS duration (<150 ms). In multivariable
analysis, there was no significant interaction between QRS duration and overall survival. Among
patients without LBBB, there was no significant difference in the cumulative rate of death from
any cause between the ICD-only and ICD-CRT groups.
Page 7
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
RAFT Trial
A second, large RCT was the Resynchronization-Defibrillation for Ambulatory Heart Failure
Trial (RAFT),11 which randomized 1798 patients with class II or III heart failure to ICD-CRT or
ICD alone, with a mean follow-up 40±20 months. Unlike most previous trials, this trial did not
confine enrollment to patients with sinus rhythm but also allowed patients with atrial arrhythmias
to participate. However, the number of patients who were not in sinus rhythm was only 12.8%
(229/1798). On formal quality assessment, this trial met all quality indicators and was given a
“good” quality rating.
The primary outcome (death from any cause or hospitalization for heart failure) was reduced in
the ICD-CRT group (33.2%) compared with the ICD-alone group (40.3%; p<0.001). There were
significant reductions in both individual components of the primary outcome, overall mortality
(20.8% vs 26.1%; p=0.003) and hospitalizations (19.5% vs 26.1%, all respectively; p<0.001).
When restricted to patients with NYHA class II heart failure, improvements in the outcomes of
mortality and hospitalizations remained significant. The mortality for class II patients in the ICDCRT group was 15.5% versus 21.1% in the ICD-alone group (HR=0.71; 95% CI, 0.56 to 0.91;
p<0.006). Hospitalizations for class II patients occurred in 16.2% of patients in the ICD-CRT
group and 21.1% in the ICD-alone group (HR=0.70; 95% CI, 0.55 to 0.89; p<0.003).
In a preplanned substudy of RAFT focusing on hospitalization rates over the 18-month follow-up
period, Gillis et al reported that the fewer patients in the ICD-CRT group (11.3%) were
hospitalized for heart failure than those in the ICD-alone group (15.6%; p=0.003).12 Although the
total number of hospitalizations for any cause was lower in the ICD-CRT group (1448 vs 1553;
p=0.042), patients randomized to ICD-CRT had more hospitalizations for device-related
indications (246 vs 159; p<0.001).
Subgroup analyses from RAFT reported that female sex, a QRS duration of 150 ms or more,
LVEF less than 20%, and QRS morphologic features were predictive of benefit. Of these factors,
QRS duration was the strongest. Patients with a QRS duration 150 ms or more had a relative risk
(RR) for the primary outcome of approximately 0.50, compared with an RR of approximately 1.0
for patients with a QRS duration less than 150 ms (p=0.003 for difference between RRs). There
was a trend for greater improvement in patients with sinus rhythm compared with patients with
atrial arrhythmias, but this difference was not statistically significant.
REVERSE Trial
The Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction
(REVERSE) trial enrolled a total of 610 patients, all of whom received a CRT device.13 Patients
were randomized to CRT-ON or CRT-OFF for a period of 12 months in double-blind fashion.
The primary outcome was a composite measure that classified patients as improved, unchanged,
or worse. There were no significant differences reported for this primary outcome. There was a
decrease in hospitalizations for heart failure in the CRT-ON group (4.1% [17/419]) compared
with the CRT-OFF group (7.9% [15/191]). Changes in functional status, as measured by the 6Page 8
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
minute walk test, were similar between groups. QOL, as measured by the MLHFQ, was also
similar between groups.
Long-term follow-up from the REVERSE trial subjects who were initially randomized to CRTON were published by Linde et al in 2013.14 At a mean follow-up of 54.8 months, 53 patients
had died, with death due to heart failure in 21 (40%), sudden cardiac death in 10 (19%), and
noncardiac causes in 22 (42%). Annualized and 5-year rates of the composite outcome of death
or first heart failure hospitalization were 6.4% and 28.1%, respectively. Five-year outcomes of
this trial were reported in 2015.15 The 5-year survival rates were estimated by regression. The
estimated absolute survival was 52.5% for the CRT group versus 29.7% for control, but this
difference was not statistically significant (p=0.21).
MIRACLE ICD Trial
The Multicenter InSync ICD Randomized Clinical Evaluation MIRACLE ICD study was the
smallest of the 3 trials enrolling 186 patients with class II heart failure and an indication for an
ICD in an unblinded fashion.16 Patients were randomized to ICD/CRT-ON or ICD/CRT-OFF
and followed for 6 months. There was no difference in the primary outcome of peak oxygen
uptake between groups. There were also no differences reported between groups for the
secondary outcomes of functional status, as measured by the 6-minute walk test, QOL, as
measured by the MLHFQ, and NYHA heart failure class.
Systematic Reviews of CRT for Heart Failure
Numerous systematic reviews and meta-analyses have been published on CRT for heart
failure.7,17-22 Most compare CRT with medical management and report that outcomes are
improved for patients with advanced heart failure and for patients with mild heart failure. For
example, a meta-analysis of 25 trials of CRT was published in 2011 by Al-Majed et al.18 This
meta-analysis focused on trials with class I or II heart failure patients, identifying 6 trials treating
4572 patients. There was a significant mortality benefit associated with CRT on combined
analysis (6 trials, 4572 participants; RR=0.83; 95% CI, 0.72 to 0.96). This mortality benefit was
driven largely by the results of RAFT, which had the most number of events and was given the
greatest weight in combined analysis. There was also a significant reduction in heart failure
hospitalizations associated with CRT use (4 trials, 4349 participants; RR=0.71; 95% CI, 0.57 to
0.87). There were no significant benefits reported for QOL, functional status, or progression to
more advanced stages of heart failure.
A meta-analysis by Chen et al (2013) evaluated studies that compared CRT plus ICD to ICD
therapy alone.23 The reviewers included 8 RCTs (total N=5674 patients) that met their inclusion
criteria. Follow-up in these studies ranged from 3 to 12 months. In pooled analysis, CRT-ICD
was associated with lower mortality than ICD therapy alone (pooled OR=0.80; 95% CI, 0.67 to
0.95) and was also associated with a lower hospitalization rate (OR=0.70; 95% CI, 0.6 to 0.81).
On subgroup analysis of studies that reported mortality at 3- to 6-month follow-up, there was a
trend toward mortality improvement with CRT-ICD, but this difference was not statistically
Page 9
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
significant (pooled OR=0.73; 95% CI, 0.46 to 1.18). Longer term follow-up outcomes beyond 1
year were not reported in the included trials.
Adverse Effects of CRT Placement
Complications in the principal RCTs were not uniformly reported; however, each trial contained
information on short- and long-term complications. Short-term complication rates ranged from
45% to 22%, with lead dislodgement and hematoma at the access site the most common. Longterm complications were reported by 2 trials,13,16 with rates of 16% and 35%, respectively. Most
long-term complications were lead dislodgement.
A systematic review was published in 2011 that focused on complications from CRT treatment.24
This analysis included 7 trials of CRT treatment that reported on in-hospital mortality and
complications related to device placement. In all 7 CRT trials, the device was placed
percutaneously without a thoracotomy. In-hospital mortality occurred at a rate of 0.3%, and 30day mortality was 0.7%. The most common complications related to placement of the left
ventricular (LV) lead. Lead dislodgement occurred in 5.9% of patients. Other LV lead placement
complications included coronary vein dissection (1.3%) and coronary vein perforation (1.3%).
Pneumothorax occurred in 0.9% of patients, and hematoma at the insertion site occurred in 2.4%
of patients.
Predictors of Response to CRT
For patients who meet indications for CRT treatment, there is a large variability in the magnitude
of response. Some patients do not respond at all, while others have very substantial benefit. As a
result, there is interest in defining the clinical features that predict response to better target
therapy toward those who will benefit most. There is a large body of literature examining
predictors of outcomes after CRT placement, and numerous clinical and demographic factors
have been identified that predict response. A smaller number of predictors have been proposed as
potential selection criteria for CRT placement.
An example of a study examining general predictors of outcome is The Predictors of Response to
Cardiac Resynchronization Therapy (PROSPECT) trial.25 This prospective, multicenter study
evaluated the utility of echocardiographic parameters to predict response to CRT. Trial results
indicated that the 12 individual echocardiographic parameters varied widely in ability to predict
response.26 The sensitivity of these individual measures ranged from 6% to 74%, and the
specificity ranged from 35% to 91%. The authors concluded it was unlikely that these measures
could improve patient selection for CRT. Two additional selection factors are reviewed here:
QRS duration/morphology and ventricular dyssynchrony on echocardiography.
QRS Duration/Morphology
It is well accepted that patients with a QRS complex of less than 120 ms who are not selected for
dyssynchrony do not benefit from CRT. LESSER-EARTH was an RCT designed to compare
CRT to no CRT in patients with a QRS complex of less than 120 ms, whether ventricular
Page 10
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
dyssynchrony was present or absent.27 This trial was terminated early after 85 patients had been
enrolled. Interim analysis revealed futility in achieving benefit on the primary outcomes, and a
trend toward greater adverse events.
A more controversial issue is whether patients with moderately prolonged QRS duration (120150 ms) benefit from CRT, or whether the benefit is confined to subsets of patients, such as
those with a markedly prolonged QRS duration (>150-160 ms) or LBBB. Several meta-analyses
of the association between QRS duration and outcomes have been published. One was a patientlevel meta-analysis that offered stronger methodology than the others. In this patient-level metaanalysis of data from 3 RCTs (total N=4076 patients), Zusterzeel et al evaluated whether women
with LBBB benefit from combined ICD-CRT implantation at a shorter QRS duration than men
with LBBB.28 For patients with LBBB and QRS duration from 130 to 149 ms, women
experienced a significant reduction in risk of heart failure or death (absolute risk difference
between ICD-CRT and ICD alone, 23%; HR=0.24; 95% CI, 0.11 to 0.53; p<0.001), while men
had no significant reduction in risk of heart failure or death (absolute risk difference, 4%;
HR=0.85; 95% CI, 0.60 to 1.21; p=0.38). Men and women with LBBB and QRS durations
longer than 150 ms benefited from ICD-CRT therapy, while neither men nor women with LBBB
and QRS durations shorter than 130 ms benefited. This trial’s conclusion is strengthened because
of the patient-level data examined, but somewhat limited because not all RCTs had patient-level
data available.
In 2011 Sipahi et al conducted a meta-analysis that evaluated whether patients with modest
prolongations of the QRS complex benefited from CRT.29 This analysis identified 5 trials (total
N=5813 patients) that reported on outcomes stratified by QRS duration. There was variability in
the definition of QRS categories, but authors were able to categorize studies into those with
moderately prolonged QRS, generally 120 to 149 ms, and severely prolonged QRS duration,
generally 150 ms or more. For patients with a moderately prolonged QRS duration, there was no
significant benefit for CRT in reducing composite outcomes of adverse cardiac events (RR=0.95;
95% CI, 0.82 to 1.10; p=0.49). In contrast, for patients with a severely prolonged QRS duration,
there was a 40% relative reduction in the composite outcomes (RR=0.60; 95% CI, 0.53 to 0.67;
p<0.001). There were no differences in outcomes on sensitivity analysis by NYHA class or ICD
status.
Other meta-analyses have come to similar conclusions, reporting benefits for patients with a
QRS of more than 150 ms, and little to no benefit for patients with shorter QRS duration.30-34 In
one of these studies, the benefit of CRT was confined to patients with LBBB.32 There was no
benefit demonstrated for patients with right bundle branch block or intraventricular conduction
delay. These reviewers suggested that QRS morphology may be as important, or more important,
than QRS duration in predicting response to CRT.
More recent individual studies have addressed the impact of QRS duration and morphology on
CRT-related outcomes. In the MADIT-CRT study, which included patients with NYHA class I
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and II heart failure (previously described), survival benefit associated with ICD-CRT
implantation was limited to patients with LBBB.10
In 2013, Peterson et al published results of a retrospective cohort study of Medicare beneficiaries
who underwent combined CRT-ICD implantation to assess associations between QRS duration
and morphology and outcomes.35 Among 24,169 patients admitted for CRT-ICD implantation
and followed for up to 3 years, rates of 3-year mortality and 1-year all-cause rehospitalization
were lowest in patients with LBBB and QRS durations of 150 ms or more. Patients with no
LBBB and QRS durations from 120 to 149 ms had an adjusted HR of 1.52 (95% CI, 1.38 to
1.67) after controlling for a number of clinical and demographic confounders (vs those with
LBBB and markedly prolonged QRS duration).
Kutyifa et al 2014 evaluated whether prolonged PR predicts heart failure or death among 537
(30%) of MADIT-CRT trial subjects who did not have a LBBB.36 Among the 96 patients with a
prolonged PR interval, compared with ICD therapy alone, ICD-CRT treatment was associated
with reduced risk of heart failure or death (HR=0.27; 95% CI, 0.13 to 0.57; p<0.001). In contrast,
among the 438 subjects with a normal PR interval, ICD-CRT treatment was associated with a
nonsignificant trend toward increased risk of heart failure or death (HR=1.45; 95% CI, 0.96 to
2.19; p=0.078).
Ventricular Dyssynchrony
Observational studies of patients who meet criteria for CRT treatment have shown that measures
of dyssynchrony on echocardiography correlate with treatment response, as defined by
improvements in LV end systolic volume, ejection fraction, or clinical criteria.37 This finding
prompted investigation of whether ventricular dyssynchrony could discriminate between
responders and nonresponders to CRT, for patients who would otherwise qualify for CRT and
for those who would not (ie, those with a narrow QRS duration).
A small RCT that compared outcomes of CRT in patients with ventricular dyssynchrony and
those without was published in 2011.38 A total of 73 patients with NYHA class II to IV heart
failure were evaluated, 44 of whom had dyssynchrony on echocardiography. These 44 patients
were randomized to a combined CRT-ICD or ICD alone. Outcomes measures were maximal
oxygen consumption (VO2max), NYHA class, and echocardiographic parameters. At 6-month
follow-up, more patients in the CRT group had an increase of at least 1 mL/kg/min in VO2max
(62% vs 50% p=0.04). There were significant within-group improvements in NYHA class and
echocardiographic measures, but between-group comparisons with the no-CRT group were not
statistically significant.
The NARROW-CRT RCT compared CRT with dual-chamber ICD among patients with heart
failure (NYHA class II/III) of ischemic origin, ejection fraction of 35% or less, QRS duration
less than 120 ms, and marked mechanical dyssynchrony on echocardiogram.39 One hundred
twenty patients were randomized to CRT (n=60) or ICD (n=60). For the study’s primary
outcome of the heart failure clinical composite score, compared with those in the ICD group,
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patients in the CRT were more likely to have an improvement in their clinical composite score at
1 year postimplantation (41% vs 16%, p=0.004). Patients in the CRT group had higher rates of
avoiding the combined end point of heart failure hospitalization, heart failure death, and
spontaneous ventricular fibrillation (p=0.028).
The EchoCRT study was intended to evaluate the role of CRT for subjects with heart failure
(NYHA class III or IV) with narrow QRS duration (<130 ms) and echocardiographic evidence of
ventricular dyssynchrony. All enrolled patients were implanted with a CRT-ICD, and then
randomized to CRT-ON or CRT-OFF. The study was stopped for futility after enrollment of 809
patients; results from the enrolled patients who had been followed for a mean of 19.4 months
were published by Ruschitzka et al.40 Four hundred four patients were randomized to the CRT
group and 405 to the control group. The primary efficacy outcome (death from any cause or
hospitalization for worsening heart failure) occurred in 116 (28.7%) of 404 patients in the CRT
group and 102 (25.2%) of 405 in the control group (HR with CRT, 1.20; 95% CI, 0.92 to 1.57;
p= 0.15). There was a significantly higher death rate in the CRT group: 45 (11.1%) of 404
patients died in the CRT group while 26 (6.4%) of 50 died in the control group (HR=1.81; 95%
CI, 1.11 to 2.93; p=0.02).
The Resynchronization Therapy in Normal QRS Trial (RethinQ study) randomized 172 patients
with a narrow QRS duration and evidence of dyssynchrony to receive a CRT device, turned on
or not, who were followed for 6 months.41 CRT-treated patients (46%) were no more likely than
non-CRT patients (41%) to show improvement (met the end point of improvement in exercise
capacity [VO2peak]). A subset of patients with QRS duration of 120 to 130 ms or more showed
improvement (p=0.02), whereas those with QRS duration less than 120 ms did not (p=0.45).
Section Summary: Cardiac Resynchronization Therapy for Heart Failure
Advanced Heart Failure (NYHA Class III/IV)
There is a large body of clinical trial evidence that supports the use of CRT in patients with
NYHA class III or IV heart failure. Results of RCTs report consistently that CRT treatment leads
to reduced mortality, improved functional status, and improved QOL for patients with NYHA
class III or IV heart failure.
Mild Heart Failure (NYHA Class I/II)
For patients with mild heart failure (NYHA class I/II), at least 4 RCTs of CRT have been
published. A mortality benefit was reported in 1 trial (RAFT). This trial was free of major bias
and reported a fairly large absolute difference in overall mortality (5.3%). None of the other 3
RCTs reported a mortality difference. While 2 of the other 3 trials were underpowered to detect
differences in mortality, MADIT-CRT was approximately the same size as RAFT and did not
show any improvement in mortality. In subgroup analysis of the MADIT-CRT trial, a mortality
benefit was shown in patients with LBB. It is possible that the sicker patient population and
longer follow-up in RAFT accounted for the mortality difference. Among other outcome
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measures, hospitalizations for heart failure showed consistent improvements, but QOL and
functional status did not. Most patients in these trials had class II congestive heart failure, as a
result it is not possible to determine separately whether patients with class I heart failure
achieved benefit. However, when mild heart failure is considered as a group (class I/II), these
data are sufficient to determine that outcomes are improved for patients with mild heart failure.
Predictors of Response
The presence of dyssynchrony on echocardiography may risk-stratify patients, but it is not a
good discriminator of responders from nonresponders. A QRS duration of more than 150 ms, or
the presence of LBBB, appears to discriminate well between responders and nonresponders and
represents a potential factor to select patients for CRT treatment. Subgroup analyses across
multiple RCTs, corroborated by quantitative pooling of these subgroup analyses in metaanalyses, have reported that a QRS duration of 150 to 160 ms or more or the presence of LBBB
are accurate in discriminating responders from nonresponders. One patient-level meta-analysis
reported that women may benefit at a shorter QRS interval than men.
CRT for Heart Failure and Atrial Fibrillation
There is controversy whether CRT leads to health outcome benefits for patients with atrial
fibrillation (AF). Many experts believe that if CRT is used, it should be combined with ablation
of the atrioventricular (AV) node to avoid transmission of atrial impulses through the node that
might result in rapid ventricular rates, thus undermining the efficacy of CRT.
A 2011 RCT compared CRT with right ventricular (RV) pacing alone in patients with AF.42 A
total of 186 patients had AV nodal ablation and implantation of a CRT device and were then
randomized to echo-optimized CRT or RV pacing alone and followed for a median of 20
months. The primary outcome measure was a composite of death from heart failure,
hospitalization for heart failure, or worsening heart failure. This combined end point occurred in
11% of the CRT group and 26% of the RV pacing group (HR=0.37; 95% CI, 0.18 to 0.73;
p=0.005). For the individual outcome measures, there was no significant reduction in mortality
(HR=1.57; 95% CI, 0.58 to 4.27; p=0.37), but there were significant reductions in
hospitalizations (HR=0.20; 95% CI, 0.06 to 0.72; p=0.013) and worsening heart failure
(HR=0.27; 95% CI, 0.12 to 0.58; p=0.37). There were no differences in outcomes on subgroup
analysis, including analysis by ejection fraction, NYHA class, and/or QRS duration.
A 2012 post hoc analysis of patients with AF enrolled in RAFT was published by Healey et al.43
Randomization in this trial was stratified for the presence of AF, allocating 114 patients with AF
to the CRT plus defibrillator group and 115 patients with AF to the defibrillator group alone.
There was no difference between groups in the primary outcome of death or hospitalization due
to heart failure (HR=0.96; 95% CI, 0.65 to 1.41; p=0.82). There were also no differences in
cardiovascular death or functional status. There was a trend for patients in the CRT group to
have fewer hospitalizations for heart failure than those in the defibrillator-alone group, but the
difference was not statistically significant.
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A 2011 systematic review compared outcomes of CRT in patients with and without AF.44 This
analysis included 23 observational studies enrolling 7495 patients, 1912 of whom had AF.
Outcomes in patients with AF were less favorable on all measures. They included overall
mortality (RR=1.5; 95% CI, 1.08 to 2.09; p=0.015), nonresponse to CRT (RR=1.32; 95% CI,
1.12 to 1.55; p=0.001), change in MLHFQ QOL score (mean difference [MD], -4.1; 95% CI, 1.7 to -6.6; p=0.001), and change in 6-minute walk distance (MD = -14.1 meters; 95% CI, -28.2
to 0.0 meters; p=0.05). Five studies compared outcomes of patients with AF who had or did not
have AV nodal ablation. Pooled analysis from these studies indicated that AV nodal ablation was
associated with a lower rate of nonresponse (RR=0.40; 95% CI, 0.28 to 0.58; p<0.001).
A 2012 systematic review evaluated the role of AV node ablation in patients with AF treated
with CRT.45 This review included nonrandomized studies that reported outcomes of CRT and
medical therapy. Six studies were included, enrolling 768 patients, 339 of whom underwent AV
node ablation and 429 who did not. AV nodal ablation was associated with improvements in the
outcomes of all-cause mortality (RR=0.42; 95% CI, 0.26 to 0.68), cardiovascular mortality
(RR=0.44; 95% CI, 0.24 to 0.81), and change in NYHA class (MD = -0.34; 95% CI, -0.56 to 0.13; p=0.002).
Yin et al published another systematic review and meta-analysis on the effects of AV nodal
ablation; it included 13 observational studies (total N=1256 patients) of CRT patients with AF
who received AV nodal ablation or medical therapy.46 In pooled analysis of patients with
inadequate biventricular pacing (<90% biventricular pacing), AV nodal ablation was associated
with lower risk of all-cause mortality than no ablation (RR=0.63; 95% CI, 0.42 to 0.96), along
with a reduced risk of CRT nonresponse (RR=0.41; 95% CI, 0.31 to 0.54). In contrast, among
patients with adequate biventricular pacing (>90% biventricular pacing), AV nodal ablation was
not significantly associated with risk of CRT nonresponse (RR=0.97; 95% CI, 0.72 to 1.32).
Section Summary: CRT for Heart Failure and Atrial Fibrillation
There is insufficient evidence to determine whether CRT improves outcomes for patients with
AF and heart failure. Data from 2 RCTs show different results, with 1 reporting improvements
for patients with AF and another reporting no significant improvements. One systematic review
of observational studies has suggested that patients with AF do not achieve the same degree of
benefit that patients with sinus rhythm do. For patients with AF undergoing CRT, a systematic
review of nonrandomized studies concluded that when CRT is used in patients with AF, AV
nodal ablation is associated with improved outcomes compared with no AV nodal ablation.
CRT for Heart Failure and AV Nodal Block
Patients with heart failure may require pacemakers for symptomatic bradycardia; those patients
have a high risk of mortality or require heart transplant due to progressive heart failure, which is
thought to be due, in part, to dyssynchronous contraction caused by RV pacing.
In 2014, the U.S. Food and Drug Administration (FDA) expanded the indications for several
CRT devices to include patients with NYHA functional class I, II, or III heart failure with LVEF
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of 50% or less, with AV block. These patients are expected to require a high percentage of
ventricular pacing that cannot be managed with algorithms to minimize RV pacing. FDA
approval was based on results of the BLOCK-HF trial, in which patients with an indication for a
pacemaker and NYHA class I, II, or III heart failure were implanted with a combined CRTpacemaker or ICD (if indicated) and randomized to standard RV pacing or biventricular pacing.47
Patients with permanent atrial arrhythmias and intrinsic AV block or AV block due to AV node
ablation could be enrolled if they met other enrollment criteria. At baseline, patients had to have
evidence that they would require a high percentage of ventricular pacing, either because of
documented third-degree AV block or a second-degree AV block or a PR interval of 300 ms or
more when paced at 100 beats per minute.
Nine-hundred eighteen patients were enrolled, 691 of whom underwent randomization after 30 to
60 days of RV pacing, during which time appropriate pharmacologic therapy was established.
Approximately half of all enrolled patients (51.6% of the CRT group, 54.1% of the RV pacing
group) had AF. After accounting for censored data due to missing measures of left ventricular
end-systolic volume (LVESV) index, the primary outcome (first event of death from any cause,
an urgent care visit for heart failure requiring intravenous therapy, or an increase in the LVESV
index of ≥15%) occurred in 160 (45.8%) of 349 patients in the biventricular pacing group and
190 (55.6%) of 342 in the RV pacing group. In a hierarchical Bayesian proportional-hazards
model, the HR for the primary outcome was 0.74 for the comparison of biventricular pacing to
RV pacing (95% CI, 0.60 to 0.90; posterior probability of HR being ≤1, 0.9978, which is greater
than the prespecified threshold for superiority of biventricular to RV pacing of 0.9775]). The
prespecified secondary outcomes of death or urgent care visit for heart failure, death or
hospitalization for heart failure, and hospitalization for heart failure were less likely in the
biventricular pacing group; however, the secondary outcome of death alone did not differ
significantly between groups. Left ventricular lead-related complications occurred in 6.4% of
patients.
Results of the BLOCK HF RCT are supported by results from the an earlier trial (PACE), in
which 177 patients with bradycardia and a normal ejection fraction in whom a biventricular
pacemaker had been implanted were randomized to biventricular pacing (n=89) or RV apical
pacing (n=88).48,49 In the trial’s main results, at 12 months postenrollment, subjects who
underwent standard pacing had lower mean LVEF than those randomized to biventricular pacing
(54.8% vs 62.2%; p<0.001) and higher mean LVESV (35.7 mL vs 27.6 mL; p<0.001). No
significant differences were reported for QOL or functional measures or in rates of heart failure
hospitalization. In long-term follow-up over a mean duration of 4.8 years among 149 subjects,
biventricular pacing continued to be associated with improved left ventricular functioning and
less left ventricular remodeling.50 In addition, during long-term follow-up, heart failure
hospitalization occurred more frequently in the RV pacing group (23.9% vs 14.6%; p<0.001).
Several other RCTs have corroborated the results of the BLOCK and PACE trials.51-53 These
additional trials report improvements in physiologic parameters of LV function, and
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improvements in functional status measured by the 6-minute walk test. Some, but not all, of
these trials also reported improvements in QOL for patients treated with CRT.
Section Summary: CRT for Heart Failure and AV Nodal Block
For patients who have AV nodal block, some degree of LV dysfunction, and who would not
necessarily meet conventional criteria for CRT but would require ventricular pacing, 1 large
RCT demonstrated improvements in heart failurerelated hospitalizations and urgent care visits
among patients treated with CRT instead of RV pacing alone. For patients who require
ventricular pacing but have no LV dysfunction, results of 1 small RCT have suggested that
biventricular pacing is associated with improved measures of cardiac function, but the trial was
small and underpowered to detect differences in clinical outcomes.
Triple-Site CRT
Triple-site CRT, or triventricular pacing, is a variation of conventional CRT that uses an
additional pacing lead. The rationale behind triventricular pacing is that a third pacing lead may
improve electromechanical synchrony, thereby leading to better outcomes. To demonstrate
improved outcomes, RCTs are needed that compare outcomes of triple-site CRT with
conventional CRT.
Five RCTs were identified for this review54-58 and are summarized in Table 1. The largest
published trial was Lenarczyk et al in 2012, which reported on the first 100 patients randomized
to triple-site or conventional CRT in the Triple-Site versus Standard Cardiac Resynchronization
Therapy Randomized Trial (TRUST CRT).56 After a follow-up of 1 year, more patients in the
conventional arm (30%) were in NYHA class III or IV heart failure than those in the triple-site
CRT group (12.5%; p<0.05). Implantation success was similar in the triple-site (94%) and
conventional groups (98%; p=NS), but triple-site implantation was associated with longer
surgical time and a higher fluoroscopic exposure. In addition, more patients in the triple-site
group required additional procedures (33% vs 16%, p<0.05).
The other 4 trials were smaller, enrolling between 43 and 76 patients. Follow-up in these studies
was generally short, with the longest being 1 year. Outcomes reported varied across studies and
were a mix of physiologic measures, functional status, and QOL. No outcome measures reported
were common across all studies. Three of the 4 studies reported significant improvements on at
least 1 outcome measure, and the fourth study reported no significant differences for the 3
outcomes measured. Adverse events were not well-reported.
Nonrandomized comparative studies also exist, but do not offer further substantive evidence on
the efficacy of triple-site CRT compared to standard CRT.59
Section Summary: Triple-Site CRT
For the use of CRT with triple-site pacing requiring implantation of an additional lead, 5 small
RCTs with limited follow-up were identified. All trials except 1 reported improved outcomes on
at least 1 measure of functional status and QOL with triple-site CRT compared with conventional
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CRT. However, the outcomes reported differed across studies, with no common outcomes
reported by all studies. Triple-site CRT was also associated with higher radiation exposure and a
greater number of additional procedures postimplantation. Larger, high-quality RCTs are needed
to better define the benefit-risk ratio for triple-site CRT compared with conventional CRT.
CRT Combined With Remote Fluid Monitoring
Intrathoracic fluid status monitoring has been proposed as a more sensitive way to monitor fluid
status leading to prompt identification of impending heart failure, permitting early intervention,
and potentially decreased rates of hospitalization.
Randomized Controlled Trials
Two RCTs were identified that compared management of patients with heart failure using
remote fluid monitoring compared to usual monitoring; these trials are summarized in Table
2.60,61 Luthje et al was an unblinded, single-site RCT sponsored by the manufacturer of the
OptiVol device.61 Patients in the remote monitoring group had alarms set for a rising fluid index,
with most patients having their diuretic increased by 50% in response to an alert. Median followup was not reported. Outcomes were reported as 1-year estimates using Cox proportional
hazards. Four patients were lost to follow-up. Domenichini et al was a unblinded, single-site
RCT sponsored by the U.K. National Health Service.60 Patients in the remote monitoring group
had alarms set for a rising fluid index, with most patients having their diuretic increased by 50%
in response to an alert. Median follow-up was 375 days (range, 350-430 days). One patient was
lost to follow-up, and 71 (89%) of 80 patients had complete data on patient reported outcomes.
Neither RCT reported improvements for the remote monitoring group on any outcome measures.
In the Domenichini study, there were no significant differences reported between groups for
hospitalizations rates, functional status, or QOL (see Table 2). Luthje reported no differences in
mortality or hospitalizations (see Table 2). In addition, Luthje reported an HR for time to first
hospitalization that was not significant at 1.23 (95% CI, 0.62 to 2.44, p=0.55). Mean number of
emergency department visits did not differ between the remote monitoring group (0.10) and the
usual care group (0.10; p=0.73), but the mean number of urgent care visits was higher for remote
monitoring (0.30) than for usual care (0.10; p=0.03).
Table 1. Randomized Controlled Trials of Triple-Site CRT Versus Standard CRT
Study
Rogers
(2012)58
P value
Lenarczyk
N
43a
100
Group
Triple-site
CRT
Standard
CRT
Triple-site
Outcomes
6MWT
MLHFQ
+91 m
-24
points
-18
points
<0.001
NR
+65 m
0.008
NR
NYHA
Class
NR
Response
Rate
NR
Ejection
Fraction
NR
QOL
12.5%b
NR
NR
NR
NR
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(2012)56
P value
Bencardino
(2016)55
P value
Anselme
(2016)54
P value
Pappone
(2015)57
CRT
Standard
CRT
30%
<0.05
43
76
44
Triple-site
CRT
Standard
CRT
NR
Triple-site
CRT
Standard
CRT
+50 m
Triple-site
CRT
Standard
CRT
NR
96%c
NR
60%
NR
<0.05
NR
78.8%
<0.001
NR
81.6%
NR
NR
+4%
+73 m
0.40
NR
+10%
NR
0.90
76%
+15%
57%
+5%
-8.4
points
-15.0
points
0.20
NR
P value
0.33
<0.001
CRT: cardiac resynchronization therapy; MLHFQ: Minnesota Living with Heart Failure Questionnaire; NR; not
reported; NYHA: New York Heart Association; QOL: quality of life; 6MWT: 6-minute walk test.
a All patients had triple-site device implanted. Device programmed to triple-site or standard CRT in random order.
b Percentage of patients in NYHA class III/IV heart failure.
c Percentage of patients who improved at least 1 NYHA class.
Table 2. Randomized Controlled Trials of Remote Monitoring With Combined Cardiac
Resynchronization Therapy and Fluid Monitoring Device
Study/Year
Domenichini
(2016)60
P value
Luthje (2015)61
N
80
176
Group
Outcomes
Mortality
Hospitalizations
6-Minute
Walk Test
+1.5 m
-53.5 m
+10 points
0.83
0.07
8.6%a
0.3 ± 0.9 per
patientb
0.2 ± 0.4 per
patient
0.95
27% (20/73)
Minnesota Living
with Heart Failure
Questionnaire
-3 points
Remote fluid
monitoring
Usual care
Remote fluid
monitoring
Usual care
4.6%
P value
0.51
NR: not reported.
a Kaplan-Meier estimate of 1-year mortality rate.
b Total
27% (22/82)
NR
hospitalizations per patient over study period
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Nonrandomized Studies
A prospective cohort of 558 patients from 34 centers identified the number of “threshold
crossing events” and the percentage of days with such events as predictors of hospitalization for
severe heart failure using multivariate regression.62 Over a mean of 326 days, 953 threshold
crossing events in 351 patients resulted in 63 hospitalizations among 49 patients. Each
subsequent event was associated with a 36% increased risk of hospitalization; however, the
extent to which the presence of threshold crossing events influenced the decision to hospitalize is
not known.
The Fluid Accumulation Status Trial (FAST) prospectively investigated use of the algorithm
used to analyze the collected bioimpedance data. In 2011, Abraham et al reported that, among
156 patients with heart failure implanted with ICD or CRT along with thoracic impedance fluid
measurements, fluid monitoring was more sensitive than daily weights in predicting worsened
heart failure (76% vs 23%, p<0.001).63
The Sensitivity of the InSync Sentry for Prediction of Heart Failure (SENSE-HF) study was
designed to prospectively evaluate the sensitivity of the OptiVol fluid trends feature in predicting
heart failure hospitalizations with signs and/or symptoms of pulmonary congestion and then to
define OptiVol clinical guidelines for patient management. Conraads et al reported results in
2011.64 The study enrolled 501 patients who underwent CRT placement with the OptiVol fluid
monitoring system. During the first 6 months postimplantation, patients and physicians were
blinded to the fluid monitoring results; following that, physicians had access to the fluid
monitoring results and patients received alerts with a “heart failure” status. In the final phase, the
physician could optimize heart failure treatment based on OptiVol results. During the first phase,
“threshold crossings” in OptiVol results led to a positive predictive value (PPV) for subsequent
heart failure hospitalizations of 4.7%. In the second phase, 233 patients received an OptiVol
alert, and for 210 their heart failure status was evaluated within 30 days. Heart failure status had
worsened for 80 patients (PPV=38.1%). The authors concluded that the intrathoracic impedance
measurements’ sensitivity improved over time but that further literature would be needed to
determine the role of thoracic impedance monitoring in clinical care.
The Combined Heart Failure Diagnostics Identify Patients at Higher Risk of Subsequent Heart
Failure Hospitalization (PARTNERS-HF) trial is a prospective, nonrandomized postmarketing
study conducted in up to 100 U.S. centers.65 It was completed in March 2008. The trial sought to
characterize the relation between various diagnostic data derived from the implanted
biventricular/ICD devices. Results, published by Whellan et al in 2010, included 694 patients
with LVEF 35% or less, NYHA class III or IV heart failure, intrinsic QRS duration of 130 ms or
more, and implanted with a commercially available CRT-ICD system.66 The authors used a
device diagnostic algorithm, which was considered positive if the patient had 2 of the following
during a 1-month period: long AF duration, rapid ventricular rate during AF, high (≥60) fluid
index, low patient activity, abnormal autonomics (high night heart rate or low heart rate
variability), notable device therapy (low CRT pacing or ICD shocks), or if they only had a very
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high (≥100) fluid index. Device diagnostics correlated with subsequent heart failure events. The
device diagnostic period was retrospective, but the heart failure prediction period was
prospective. After adjusting for clinical variables, patients with a positive device diagnostic
algorithm had a significantly higher risk of heart failure hospitalization with pulmonary signs or
symptoms within the next month (adjusted HR=4.8; 95% CI, 2.9 to 8.1; p<0.001).
A number of retrospective studies have evaluated the correlation between in-device diagnostics
and outcomes.
Gula et al used data from RAFT to validate the integrated diagnostics algorithm, which uses data
related to heart rate and rhythm, intrathoracic fluid monitoring, and activity to create a risk score,
from 1224 patients with implanted devices (741 with combined ICD-CRT devices, 483 with
ICDs alone).67 Compared with low-risk months, the RR of heart failure admission in months
considered high risk, based on the integrated diagnostics algorithm during high-risk months, was
10.7 (95 % CI, 6.9 to 16.6).
Sekiguchi et al retrospectively evaluated “threshold crossings” as a predictor of arrhythmogenic
events among 282 patients with NYHA class III or IV heart failure followed for a mean of 10
months.68 Patients were classified into those who had “threshold crossings” (145 [51%]) and
those who did not (137 [49%]). Tachyarrhythmic events were more common in patients with
threshold crossings (3241 events) than in patients without (1484 events; p<0.001).
Section Summary: CRT Combined With Remote Fluid Monitoring
Two small RCTs have reported no improvement in outcomes associated with remote fluid
monitoring for patients with heart failure. These RCTs have methodologic limitations, which
while not definitively ruling out a benefit, do not a support a benefit from remote monitoring of
fluid status versus usual care. In addition to the RCT evidence, other studies report that
intrathoracic monitoring algorithms are associated with heart failure episodes and may be a more
sensitive measure for predicting heart failure exacerbations than weight monitoring. However,
this evidence does not address the impact of fluid monitoring on outcomes. The evidence is not
sufficient to determine whether intrathoracic fluid monitoring improves outcomes for patients
who receive a CRT device.
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this review are listed in Table 3.
Table 3. Summary of Key Active Trials
NCT No.
Ongoing
NCT01786993
NCT01522898a
NCT02150538
Trial Name
Planned
Enrollment
Completion
Date
MultiPoint Pacing IDE Study
506
Cardiac Resynchronisation Therapy and AV Nodal Ablation Trial in
Atrial Fibrillation (CAAN-AF)
BiventRicular Pacing in prolongEd Atrio-Ventricular intervaL: the
590
Apr 2015
(ongoing)
Jul 2016
164
Dec 2016
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MEDICAL POLICY
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BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
NCT01482598
NCT01994252
NCT02137187
Unpublished
NCT01735916a
NCT00941850
REAL-CRT Study
Clinical Benefits in Optimized Remote HF Patient Management
Resynchronization/Defibrillation for Ambulatory Heart Failure Trial
in Patients With Permanent Atrial Fibrillation (RAFT-PermAF)
A Randomized Controlled Trial of Atrioventricular (AV) Junction
Ablation and Biventricular Pacing Versus Optimal Pharmacological
Therapy in Patients With Permanent Atrial Fibrillation
MIRACLE EF Clinical Study
TRIple-site VENTricular Pacing in Non-responders to Conventional
Dual Ventricular Site Cardiac Resynchronization Therapy
NCT01510652a More Options Available With a Quadripolar Left Ventricular (LV)
Lead pRovide In-clinic Solutions to Cardiac Resynchronization
Therapy (CRT) Challenges (MORE-CRT)
NCT00187278
Biventricular Pacing for Atrioventricular Block in Left Ventricular
Dysfunction to Prevent Cardiac Desynchronization
NCT00769457a OptiLink HF Study (Optimization of Heart Failure Management
Using Medtronic OptiVol® Fluid Status Monitoring and Medtronic
CareLink® Network)
NCT: national clinical trial.
a Denotes industry-sponsored or cosponsored trial.
438
950
Aug 2018
Dec 2018
1830
May 2019
44
20
Terminated
Nov 2012
(completed)
May 2014
(completed)
1078
1833
1000
Oct 2014
(completed)
Nov 2014
(completed)
Summary of Evidence
For individuals who have advanced heart failure (New York Heart Association [NYHA] class
III/IV) who receive cardiac resynchronization therapy (CRT), the evidence includes randomized
controlled trials (RCTs) and systematic reviews of RCTs. Relevant outcomes are overall
survival, symptoms, functional outcomes, quality of life, hospitalizations, and treatment-related
morbidity. There is a large body of clinical trial evidence supporting use of CRT in patients with
NYHA class III or IV heart failure. The RCTs have consistently reported that CRT treatment
reduces mortality, improves functional status, and improves quality of life for patients with
NYHA class III or IV heart failure. Multiple subgroup analyses of RCTs have demonstrated that
the benefit of CRT is mainly restricted to patients with left bundle branch block (LBBB) or QRS
duration greater than 150 ms. The evidence is sufficient to determine quantitatively that the
technology results in a meaningful improvement in the net health outcome.
For individuals who have mild heart failure (New York Heart Association class I/II) who receive
CRT, the evidence includes RCTs and systematic reviews of RCTs. Relevant outcomes are
overall survival, symptoms, functional outcomes, quality of life, hospitalizations, and treatmentrelated morbidity. For patients with mild heart failure (NYHA class I/II), at least 4 RCTs of CRT
have been published. A mortality benefit was reported in 1 of the 4 trials, the RAFT trial. None
of the other 3 RCTs reported a mortality difference, but a subgroup analysis of the MADIT-CRT
trial reported a mortality benefit for patients with LBBB. Among other outcome measures,
hospitalizations for heart failure showed consistent improvements, but quality of life and
functional status did not. Multiple subgroup analyses of RCTs have demonstrated that the benefit
of CRT is mainly restricted to patients with LBBB or QRS duration greater than 150 ms. The
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MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
evidence is sufficient to determine qualitatively that the technology results in a meaningful
improvement in the net health outcome.
For individuals who have heart failure and atrial fibrillation who receive CRT, the evidence
includes 2 RCTs and observational studies. Relevant outcomes are overall survival, symptoms,
functional outcomes, quality of life, hospitalizations, and treatment-related morbidity. Data from
2 RCTs have reported conflicting results, with 1 reporting improvements for patients with atrial
fibrillation (AF) and another reporting no significant improvements. One systematic review of
observational studies has suggested that patients with AF do not benefit the same degree as
patients with sinus rhythm. The evidence is insufficient to determine the effects of the
technology on health outcomes.
For individuals who have heart failure and atrioventricular (AV) nodal block who receive CRT,
the evidence includes RCTs and systematic reviews of RCTs. Relevant outcomes are overall
survival, symptoms, functional outcomes, quality of life, hospitalizations, and treatment-related
morbidity. One large RCT demonstrated that CRT led to improvements in heart failurerelated
hospitalizations and urgent care visits among patients with heart failure and AV block but who
would not necessarily meet conventional criteria for CRT. For patients who require ventricular
pacing but have no left ventricular dysfunction, results of 1 small RCT have suggested that
biventricular pacing is associated with improved measures of cardiac function, but the trial was
small and underpowered to detect differences in clinical outcomes. The evidence is sufficient to
determine qualitatively that the technology results in a meaningful improvement in the net health
outcome.
For individuals who have heart failure who receive triple-site CRT, the evidence includes small
RCTs. Relevant outcomes are overall survival, symptoms, functional outcomes, quality of life,
hospitalizations, and treatment-related morbidity. The available RCTs have reported improved
outcomes on at least 1 measure of functional status or quality of life with triple-site CRT
compared to conventional CRT. However, the trials are small and have methodologic limitations.
In addition, outcomes reported differed across studies. Triple-site CRT was also associated with
higher radiation exposure and a greater number of additional procedures postimplantation.
Larger, high-quality RCTs are needed to better define the benefit-risk ratio for triple-site CRT
compared to conventional CRT. The evidence is insufficient to determine the effects of the
technology on health outcomes.
For individuals who have heart failure who receive CRT combined with remote fluid monitoring,
the evidence includes 2 RCTs and nonrandomized studies. Relevant outcomes are overall
survival, symptoms, functional outcomes, quality of life, hospitalizations, and treatment-related
morbidity. Two small RCTs have reported no improvement in outcomes associated with remote
fluid monitoring for patients with heart failure. These RCTs have methodologic limitations,
which while not definitively ruling out a benefit, do not a support a benefit from remote
monitoring of fluid status versus usual care. In addition to the RCT evidence, other studies have
reported that intrathoracic monitoring algorithms are associated with heart failure episodes and
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MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
may be a more sensitive measure for predicting heart failure exacerbations compared with
weight monitoring. However, this evidence does not address the impact of fluid monitoring on
outcomes. The evidence is insufficient to determine the effects of the technology on health
outcomes.
Clinical Input Received From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate
with and make recommendations during this process, through the provision of appropriate
reviewers, input received does not represent an endorsement or position statement by the
physician specialty societies or academic medical centers, unless otherwise noted.
In response to requests, input was received from 8 academic medical centers and 1 physician
specialty society while this policy was under review in 2012. There was consensus agreement
with the medically necessary statements. For patients with class I heart failure, there was mixed
input as to whether CRT should be medically necessary. Regarding the duration of the QRS
complex, there was acknowledgement that the literature supported use mainly in patients with a
QRS duration greater than 150 ms, but most reviewers disagreed with restricting CRT use to
patients in that group because that duration was not currently the accepted standard of care. For
patients with AF, the input was mixed on whether biventricular pacing improves outcomes.
Practice Guidelines and Position Statements
American College of Cardiology, American Heart Association, and Heart Rhythm Society
In 2013, the American College of Cardiology (ACC) and American Heart Association (AHA)
published guidelines for the management of heart failure.69 These guidelines make
recommendations on CRT for heart failure that are in line with those made by the ACC/AHA
and Heart Rhythm Society related to CRT for heart failure outlined next.
A focused update to 2008 guidelines70 for device-based treatment of cardiac rhythm
abnormalities were published jointly by ACC, AHA, and the Heart Rhythm Society in 2012.71
These guidelines included the following recommendations on CRT for heart failure:
Class I Recommendations
 CRT is indicated for patients who have LVEF (left ventricular ejection fraction) less than
or equal to 35%, sinus rhythm, LBBB (left bundle branch block) with a QRS duration
greater than or equal to 150 ms, and NYHA class II, III, or ambulatory IV symptoms on
guideline-directed medical therapy (GDMT). (Level of Evidence: A for NYHA class
III/IV; Level of Evidence: B for NYHA class II)
Class IIa Recommendations
 CRT can be useful for patients who have LVEF less than or equal to 35%, sinus rhythm,
LBBB with a QRS duration 120 to 149 ms, and NYHA class II, III, or ambulatory IV
symptoms on GDMT. (Level of Evidence: B)
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BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007



CRT can be useful for patients who have LVEF less than or equal to 35%, sinus rhythm,
a non-LBBB pattern with a QRS duration greater than or equal to 150 ms, and NYHA
class III/ambulatory class IV symptoms on GDMT. (Level of Evidence: A)
CRT can be useful in patients with atrial fibrillation and LVEF less than or equal to 35%
on GDMT if a) the patient requires ventricular pacing or otherwise meets CRT criteria
and b) AV nodal ablation or pharmacologic rate control will allow near 100% ventricular
pacing with CRT. (Level of Evidence: B)
CRT can be useful for patients on GDMT who have LVEF less than or equal to 35% and
are undergoing new or replacement device placement with anticipated requirement for
significant (>40%) ventricular pacing. (Level of Evidence: C)
Class IIb Recommendations
 CRT may be considered for patients who have LVEF less than or equal to 30%, ischemic
etiology of heart failure, sinus rhythm, LBBB with a QRS duration of greater than or
equal to 150 ms, and NYHA class I symptoms on GDMT. (Level of Evidence: C)
 CRT may be considered for patients who have LVEF less than or equal to 35%, sinus
rhythm, a non-LBBB pattern with QRS duration 120 to 149 ms, and NYHA class
III/ambulatory class IV on GDMT. (Level of Evidence: B)
 CRT may be considered for patients who have LVEF less than or equal to 35%, sinus
rhythm, a non-LBBB pattern with a QRS duration greater than or equal to 150 ms, and
NYHA class II symptoms on GDMT. (Level of Evidence: B)
Class III Recommendations (no benefit)
 CRT is not recommended for patients with NYHA class I or II symptoms and nonLBBB pattern with QRS duration less than 150 ms. (Level of Evidence: B)
 CRT is not indicated for patients whose comorbidities and/or frailty limit survival
with good functional capacity to less than 1 year. (Level of Evidence: C)
European Society of Cardiology and European Heart Rhythm Association
The European Society of Cardiology and the European Heart Rhythm Association released
guidelines on cardiac pacing and cardiac resynchronization therapy in 2013.72 These guidelines
included the following recommendations on CRT for heart failure with sinus rhythm:
Class I Recommendations
 LBBB with QRS duration greater than 150 ms. CRT is recommended in chronic heart
failure patients and LVEF less than or equal to 35% who remain in NYHA functional
class II, III, and ambulatory IV despite adequate medical treatment. (Level of
Evidence: A).
 LBBB with QRS duration from 120 to 150 ms. CRT is recommended in chronic heart
failure patients and LVEF less than or equal to 35% who remain in NYHA functional
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BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
class II, III, and ambulatory IV despite adequate medical treatment. (Level of
Evidence: B).
Class IIa Recommendations
 Non-LBBB with QRS duration greater than 150 ms. CRT should be considered in
chronic heart failure patients and LVEF less than or equal to 35% who remain in
NYHA functional class II, III, and ambulatory IV despite adequate medical treatment.
(Level of Evidence: B).
Class IIb Recommendations
 Non-LBBB with QRS duration 120-150 ms. CRT may be considered in chronic heart
failure patients and LVEF less than or equal to 35% who remain in NYHA functional
class II, III, and ambulatory IV despite adequate medical treatment. (Level of
Evidence: B).
Class III Recommendations
 CRT in patients with chronic heart failure with QRS duration less than 120 ms is not
recommended (Level of Evidence: B).
Heart Failure Society of America
The Heart Failure Society of America released comprehensive guidelines on the management of
heart failure in 2010.73 The guidelines include the following recommendations related to the use
of CRT:





Biventricular pacing therapy is recommended for patients in sinus rhythm with a
widened QRS interval (≥120 ms) and severe LV [left ventricular] systolic dysfunction
(LVEF ≤ 35%) who have persistent, moderate to severe HF (NYHA III) despite
optimal medical therapy. (Level of Evidence: A).
Biventricular pacing therapy may be considered for patients with atrial fibrillation
with a widened QRS interval (≥120 ms) and severe LV systolic dysfunction LVEF
≤35% who have persistent, moderate to severe HF (NYHA III) despite optimal
medical therapy. (Level of Evidence: B).
Selected ambulatory NYHA IV patients in sinus rhythm with QRS ≥120 ms and LV
systolic dysfunction may be considered for biventricular pacing therapy. (Level of
Evidence: B).
Biventricular pacing therapy may be considered in patients with reduced LVEF and
QRS ≥ 150 ms who have NYHA I or II HF symptoms. (Level of Evidence: B).
In patients with reduced LVEF who require chronic pacing and in whom frequent
ventricular pacing is expected, biventricular pacing may be considered. (Level of
Evidence: C).
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MEDICAL POLICY
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BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
U.S. Preventive Services Task Force Recommendations
Not applicable.
V.
DEFINITIONS
TOP
ARRHYTHMIA REFERS to irregularity, or loss of rhythm, of the heart.
NEW YORK HEART ASSOCIATION 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.
NEW YORK HEART ASSOCIATION CLASS II -Patients with cardiac disease resulting in slight
limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in
fatigue, palpitation, dyspnea or anginal pain.
NEW YORK HEART ASSOCIATION 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.
NEW YORK HEART ASSOCIATION 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
increases.
PREMARKET APPROVAL (PMA) is the FDA process of scientific and regulatory review to
evaluate the safety and effectiveness of Class III medical devices. Class III devices are those
that support or sustain human life, are of substantial importance in preventing impairment of
human health, or which present a potential, unreasonable risk of illness or injury.
VI. BENEFIT VARIATIONS
TOP
The existence of this medical policy does not mean that this service is a covered benefit under
the member's contract. Benefit determinations should be based in all cases on the applicable
contract language. Medical policies do not constitute a description of benefits. A member’s
individual or group customer benefits govern which services are covered, which are excluded,
and which are subject to benefit limits and which require preauthorization. Members and
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MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
providers should consult the member’s benefit information or contact Capital for benefit
information.
VII. DISCLAIMER
TOP
Capital’s medical policies are developed to assist in administering a member’s benefits, do not constitute medical
advice and are subject to change. Treating providers are solely responsible for medical advice and treatment of
members. Members should discuss any medical policy related to their coverage or condition with their provider
and consult their benefit information to determine if the service is covered. If there is a discrepancy between this
medical policy and a member’s benefit information, the benefit information will govern. Capital considers the
information contained in this medical policy to be proprietary and it may only be disseminated as permitted by law.
VIII. CODING INFORMATION
TOP
Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The
identification of a code in this section does not denote coverage as coverage is determined by
the terms of member benefit information. In addition, not all covered services are eligible for
separate reimbursement.
Intrathoracic fluid-monitoring sensor is considered investigational as a component of a
biventricular pacemaker and Triple-site (triventricular) CRT, using an additional pacing
lead is also considered investigational; therefore not covered:
CPT Codes®
33229
33264
33999
Current Procedural Terminology (CPT) copyrighted by American Medical Association. All Rights Reserved.
HCPCS
Code
C2621
Description
Pacemaker, other than single or dual chamber (implantable)
Covered when medically necessary:
CPT
Codes ®
33202
33217
33263
33203
33224
33264
33206
33225
33207
33228
33208
33229
33212
33230
33213
33240
33214
33249
Current Procedural Terminology (CPT) copyrighted by American Medical Association. All Rights Reserved.
Page 28
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
HCPCS
Code
C1721
C1777
C1895
C1899
G0448
Description
Cardioverter- defibrillator, dual chamber (implantable)
Lead, cardio-defibrillator, endocardial single coil (implantable)
Lead, cardioverter-defibrillator, endocardial dual coil (implantable
Lead, pacemaker/cardioverter-defibrillator combination (implantable
Insertion or replacement of a permanent pacing cardioverter-defibrillator system with
transvenous lead(s), single or dual chamber with insertion of pacing electrode, cardiac venous
system, for left ventricular pacing
ICD-10-CM
Diagnosis
Code*
I09.81
I11.0
I50.1
I50.20
I50.21
I50.22
I50.23
I50.30
I50.31
I50.32
I50.33
I50.40
I50.41
I50.42
I50.43
Description
Rheumatic heart failure
Hypertensive heart disease with heart failure
Left ventricular failure
Unspecified systolic (congestive) heart failure
Acute systolic (congestive) heart failure
Chronic systolic (congestive) heart failure
Acute on chronic systolic (congestive) heart failure
Unspecified diastolic (congestive) heart failure
Acute diastolic (congestive) heart failure
Chronic diastolic (congestive) heart failure
Acute on chronic diastolic (congestive) heart failure
Unspecified combined systolic (congestive) and diastolic (congestive) heart failure
Acute combined systolic (congestive) and diastolic (congestive) heart failure
Chronic combined systolic (congestive) and diastolic (congestive) heart failure
Acute on chronic combined systolic (congestive) and diastolic (congestive) heart failure
*If applicable, please see Medicare LCD or NCD for additional covered diagnoses.
IX. REFERENCES
TOP
1. FDA. Summary of Safety and Effectiveness Data: Tupos LV/ATx CRT-D, Kronos LV-T CRTD. 2006; http://www.accessdata.fda.gov/cdrh_docs/pdf5/P050023b.pdf. Accessed August 26,
2016.
2. FDA. Approval Order: Biotronic PMA P050023. 2013;
http://www.accessdata.fda.gov/cdrh_docs/pdf5/P050023S058A.pdf. Accessed August 26,
2016.
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MEDICAL POLICY
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BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
3. Administration FaD. Summary of Safety and Effectiveness Data: Cardiac Resynchronization
Therapy Defibrillator (CRT-D). 2010;
http://www.accessdata.fda.gov/cdrh_docs/pdf/P010012S230b.pdf. Accessed August 26, 2016.
4. Hunt SA. ACC/AHA 2005 guideline update for the diagnosis and management of chronic
heart failure in the adult: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines (Writing Committee to Update the 2001
Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol. Sep 20
2005;46(6):e1-82. PMID 16168273
5. Cardiac resynchronization therapy for mild congestive heart failure. Blue Cross and Blue
Shield Association Technology Evaluation Center TEC Assessment Program. 2009;24(8).
PMID
6. 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. May 20
2004;350(21):2140-2150. PMID 15152059
7. McAlister FA, Ezekowitz JA, Wiebe N, et al. Systematic review: cardiac resynchronization in
patients with symptomatic heart failure. Ann Intern Med. Sep 7 2004;141(5):381-390. PMID
15353430
8. Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention
of heart-failure events. N Engl J Med. Oct 1 2009;361(14):1329-1338. PMID 19723701
9. Goldenberg I, Hall WJ, Beck CA, et al. Reduction of the risk of recurring heart failure events
with cardiac resynchronization therapy: MADIT-CRT (Multicenter Automatic Defibrillator
Implantation Trial With Cardiac Resynchronization Therapy). J Am Coll Cardiol. Aug 9
2011;58(7):729-737. PMID 21816309
10. Goldenberg I, Kutyifa V, Klein HU, et al. Survival with cardiac-resynchronization therapy in
mild heart failure. N Engl J Med. May 1 2014;370(18):1694-1701. PMID 24678999
11. Tang AS, Wells GA, Talajic M, et al. Cardiac-resynchronization therapy for mild-tomoderate heart failure. N Engl J Med. Dec 16 2010;363(25):2385-2395. PMID 21073365
12. Gillis AM, Kerr CR, Philippon F, et al. Impact of cardiac resynchronization therapy on
hospitalizations in the Resynchronization-Defibrillation for Ambulatory Heart Failure trial.
Circulation. May 20 2014;129(20):2021-2030. PMID 24610807
13. 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. Dec 2
2008;52(23):1834-1843. PMID 19038680
14. Linde C, Gold MR, Abraham WT, et al. Long-term impact of cardiac resynchronization
therapy in mild heart failure: 5-year results from the REsynchronization reVErses
Remodeling in Systolic left vEntricular dysfunction (REVERSE) study. Eur Heart J. Sep
2013;34(33):2592-2599. PMID 23641006
15. Gold MR, Padhiar A, Mealing S, et al. Long-term extrapolation of clinical benefits among
patients with mild heart failure receiving cardiac resynchronization therapy: analysis of the
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BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
5-year follow-up from the REVERSE Study. JACC Heart Fail. Sep 2015;3(9):691-700. PMID
26277764
16. Abraham WT, Young JB, Leon AR, et al. Effects of cardiac resynchronization on disease
progression in patients with left ventricular systolic dysfunction, an indication for an
implantable cardioverter-defibrillator, and mildly symptomatic chronic heart failure.
Circulation. Nov 2 2004;110(18):2864-2868. PMID 15505095
17. Adabag S, Roukoz H, Anand IS, et al. Cardiac resynchronization therapy in patients with
minimal heart failure: a systematic review and meta-analysis. J Am Coll Cardiol. Aug 23
2011;58(9):935-941. PMID 21851882
18. Al-Majed NS, McAlister FA, Bakal JA, et al. Meta-analysis: cardiac resynchronization
therapy for patients with less symptomatic heart failure. Ann Intern Med. Mar 15
2011;154(6):401-412. PMID 21320922
19. Bertoldi EG, Polanczyk CA, Cunha V, et al. Mortality reduction of cardiac resynchronization
and implantable cardioverter-defibrillator therapy in heart failure: an updated metaanalysis. Does recent evidence change the standard of care? J Card Fail. Oct
2011;17(10):860-866. PMID 21962425
20. Nery PB, Ha AC, Keren A, et al. Cardiac resynchronization therapy in patients with left
ventricular systolic dysfunction and right bundle branch block: a systematic review. Heart
Rhythm. Jul 2011;8(7):1083-1087. PMID 21300176
21. Tu R, Zhong G, Zeng Z, et al. Cardiac resynchronization therapy in patients with mild heart
failure: a systematic review and meta-analysis of randomized controlled trials. Cardiovasc
Drugs Ther. Aug 2011;25(4):331-340. PMID 21750900
22. Wells G, Parkash R, Healey JS, et al. Cardiac resynchronization therapy: a meta-analysis of
randomized controlled trials. CMAJ. Mar 8 2011;183(4):421-429. PMID 21282316
23. Chen S, Ling Z, Kiuchi MG, et al. The efficacy and safety of cardiac resynchronization
therapy combined with implantable cardioverter defibrillator for heart failure: a metaanalysis of 5674 patients. Europace. Jul 2013;15(7):992-1001. PMID 23419662
24. van Rees JB, de Bie MK, Thijssen J, et al. Implantation-related complications of implantable
cardioverter-defibrillators and cardiac resynchronization therapy devices: a systematic
review of randomized clinical trials. J Am Coll Cardiol. Aug 30 2011;58(10):995-1000.
PMID 21867832
25. Yu CM, Abraham WT, Bax J, et al. Predictors of response to cardiac resynchronization
therapy (PROSPECT)--study design. Am Heart J. Apr 2005;149(4):600-605. PMID
15990740
26. Chung ES, Leon AR, Tavazzi L, et al. Results of the Predictors of Response to CRT
(PROSPECT) trial. Circulation. May 20 2008;117(20):2608-2616. PMID 18458170
27. Thibault B, Harel F, Ducharme A, et al. Cardiac resynchronization therapy in patients with
heart failure and a qrs complex <120 milliseconds: the evaluation of resynchronization
therapy for heart failure (LESSER-EARTH) Trial. Circulation. Feb 26 2013;127(8):873-881.
PMID 23388213
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THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
28. Zusterzeel R, Selzman KA, Sanders WE, et al. Cardiac resynchronization therapy in women:
US Food and Drug Administration meta-analysis of patient-level data. JAMA Intern Med.
Aug 2014;174(8):1340-1348. PMID 25090172
29. Sipahi I, Carrigan TP, Rowland DY, et al. Impact of QRS duration on clinical event
reduction with cardiac resynchronization therapy: meta-analysis of randomized controlled
trials. Arch Intern Med. Sep 12 2011;171(16):1454-1462. PMID 21670335
30. Bryant AR, Wilton SB, Lai MP, et al. Association between QRS duration and outcome with
cardiac resynchronization therapy: a systematic review and meta-analysis. J Electrocardiol.
Mar-Apr 2013;46(2):147-155. PMID 23394690
31. Stavrakis S, Lazzara R, Thadani U. The benefit of cardiac resynchronization therapy and
QRS duration: a meta-analysis. J Cardiovasc Electrophysiol. Feb 2012;23(2):163-168.
PMID 21815961
32. Sipahi I, Chou JC, Hyden M, et al. Effect of QRS morphology on clinical event reduction
with cardiac resynchronization therapy: meta-analysis of randomized controlled trials. Am
Heart J. Feb 2012;163(2):260-267 e263. PMID 22305845
33. Kang SH, Oh IY, Kang DY, et al. Cardiac resynchronization therapy and QRS duration:
systematic review, meta-analysis, and meta-regression. J Korean Med Sci. Jan
2015;30(1):24-33. PMID 25552880
34. Shah RM, Patel D, Molnar J, et al. Cardiac-resynchronization therapy in patients with
systolic heart failure and QRS interval </=130 ms: insights from a meta-analysis. Europace.
Feb 2015;17(2):267-273. PMID 25164431
35. Peterson PN, Greiner MA, Qualls LG, et al. QRS duration, bundle-branch block
morphology, and outcomes among older patients with heart failure receiving cardiac
resynchronization therapy. JAMA. Aug 14 2013;310(6):617-626. PMID 23942680
36. Kutyifa V, Stockburger M, Daubert JP, et al. PR interval identifies clinical response in
patients with non-left bundle branch block: a multicenter automatic defibrillator
implantation trial-cardiac resynchronization therapy substudy. Circ Arrhythm
Electrophysiol. Aug 2014;7(4):645-651. PMID 24963007
37. Hawkins NM, Petrie MC, MacDonald MR, et al. Selecting patients for cardiac
resynchronization therapy: electrical or mechanical dyssynchrony? Eur Heart J. Jun
2006;27(11):1270-1281. PMID 16527827
38. Diab IG, Hunter RJ, Kamdar R, et al. Does ventricular dyssynchrony on echocardiography
predict response to cardiac resynchronisation therapy? A randomised controlled study.
Heart. Sep 2011;97(17):1410-1416. PMID 21700757
39. Muto C, Solimene F, Gallo P, et al. A randomized study of cardiac resynchronization therapy
defibrillator versus dual-chamber implantable cardioverter-defibrillator in ischemic
cardiomyopathy with narrow QRS: the NARROW-CRT study. Circ Arrhythm Electrophysiol.
Jun 2013;6(3):538-545. PMID 23592833
Page 32
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
40. Ruschitzka F, Abraham WT, Singh JP, et al. Cardiac-resynchronization therapy in heart
failure with a narrow QRS complex. N Engl J Med. Oct 10 2013;369(15):1395-1405. PMID
23998714
41. Beshai JF, Grimm RA, Nagueh SF, et al. Cardiac-resynchronization therapy in heart failure
with narrow QRS complexes. N Engl J Med. Dec 13 2007;357(24):2461-2471. PMID
17986493
42. Brignole M, Botto G, Mont L, et al. Cardiac resynchronization therapy in patients
undergoing atrioventricular junction ablation for permanent atrial fibrillation: a randomized
trial. Eur Heart J. Oct 2011;32(19):2420-2429. PMID 21606084
43. Healey JS, Hohnloser SH, Exner DV, et al. Cardiac resynchronization therapy in patients
with permanent atrial fibrillation: results from the Resynchronization for Ambulatory Heart
Failure Trial (RAFT). Circ Heart Fail. Sep 1 2012;5(5):566-570. PMID 22896584
44. Wilton SB, Leung AA, Ghali WA, et al. Outcomes of cardiac resynchronization therapy in
patients with versus those without atrial fibrillation: a systematic review and meta-analysis.
Heart Rhythm. Jul 2011;8(7):1088-1094. PMID 21338711
45. Ganesan AN, Brooks AG, Roberts-Thomson KC, et al. Role of AV nodal ablation in cardiac
resynchronization in patients with coexistent atrial fibrillation and heart failure a systematic
review. J Am Coll Cardiol. Feb 21 2012;59(8):719-726. PMID 22340263
46. Yin J, Hu H, Wang Y, et al. Effects of atrioventricular nodal ablation on permanent atrial
fibrillation patients with cardiac resynchronization therapy: a systematic review and metaanalysis. Clin Cardiol. Nov 2014;37(11):707-715. PMID 25156448
47. Curtis AB, Worley SJ, Adamson PB, et al. Biventricular pacing for atrioventricular block
and systolic dysfunction. N Engl J Med. Apr 25 2013;368(17):1585-1593. PMID 23614585
48. Yu CM, Chan JY, Zhang Q, et al. Biventricular pacing in patients with bradycardia and
normal ejection fraction. N Engl J Med. Nov 26 2009;361(22):2123-2134. PMID 19915220
49. Chan JY, Fang F, Zhang Q, et al. Biventricular pacing is superior to right ventricular pacing
in bradycardia patients with preserved systolic function: 2-year results of the PACE trial.
Eur Heart J. Oct 2011;32(20):2533-2540. PMID 21875860
50. Yu CM, Fang F, Luo XX, et al. Long-term follow-up results of the pacing to avoid cardiac
enlargement (PACE) trial. Eur J Heart Fail. Sep 2014;16(9):1016-1025. PMID 25179592
51. Doshi RN, Daoud EG, Fellows C, et al. Left ventricular-based cardiac stimulation post AV
nodal ablation evaluation (the PAVE study). J Cardiovasc Electrophysiol. Nov
2005;16(11):1160-1165. PMID 16302897
52. Kindermann M, Hennen B, Jung J, et al. Biventricular versus conventional right ventricular
stimulation for patients with standard pacing indication and left ventricular dysfunction: the
Homburg Biventricular Pacing Evaluation (HOBIPACE). J Am Coll Cardiol. May 16
2006;47(10):1927-1937. PMID 16697307
53. Martinelli Filho M, de Siqueira SF, Costa R, et al. Conventional versus biventricular pacing
in heart failure and bradyarrhythmia: the COMBAT study. J Card Fail. Apr 2010;16(4):293300. PMID 20350695
Page 33
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
54. Anselme F, Bordachar P, Pasquie JL, et al. Safety, feasibility, and outcome results of cardiac
resynchronization with triple-site ventricular stimulation compared to conventional cardiac
resynchronization. Heart Rhythm. Jan 2016;13(1):183-189. PMID 26325531
55. Bencardino G, Di Monaco A, Russo E, et al. Outcome of patients treated by cardiac
resynchronization therapy using a quadripolar left ventricular lead. Circ J. Feb 25
2016;80(3):613-618. PMID 26821688
56. Lenarczyk R, Kowalski O, Sredniawa B, et al. Implantation feasibility, procedure-related
adverse events and lead performance during 1-year follow-up in patients undergoing triplesite cardiac resynchronization therapy: a substudy of TRUST CRT randomized trial. J
Cardiovasc Electrophysiol. Nov 2012;23(11):1228-1236. PMID 22651239
57. Pappone C, Calovic Z, Vicedomini G, et al. Improving cardiac resynchronization therapy
response with multipoint left ventricular pacing: Twelve-month follow-up study. Heart
Rhythm. Jun 2015;12(6):1250-1258. PMID 25678057
58. Rogers DP, Lambiase PD, Lowe MD, et al. A randomized double-blind crossover trial of
triventricular versus biventricular pacing in heart failure. Eur J Heart Fail. May
2012;14(5):495-505. PMID 22312038
59. Ogano M, Iwasaki YK, Tanabe J, et al. Antiarrhythmic effect of cardiac resynchronization
therapy with triple-site biventricular stimulation. Europace. Oct 2013;15(10):1491-1498.
PMID 23696627
60. Domenichini G, Rahneva T, Diab IG, et al. The lung impedance monitoring in treatment of
chronic heart failure (the L1.
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MEDICAL POLICY
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BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
6. 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. May 20
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14. Linde C, Gold MR, Abraham WT, et al. Long-term impact of cardiac resynchronization
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26277764
16. Abraham WT, Young JB, Leon AR, et al. Effects of cardiac resynchronization on disease
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2011;58(9):935-941. PMID 21851882
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MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
18. Al-Majed NS, McAlister FA, Bakal JA, et al. Meta-analysis: cardiac resynchronization
therapy for patients with less symptomatic heart failure. Ann Intern Med. Mar 15
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19. Bertoldi EG, Polanczyk CA, Cunha V, et al. Mortality reduction of cardiac resynchronization
and implantable cardioverter-defibrillator therapy in heart failure: an updated metaanalysis. Does recent evidence change the standard of care? J Card Fail. Oct
2011;17(10):860-866. PMID 21962425
20. Nery PB, Ha AC, Keren A, et al. Cardiac resynchronization therapy in patients with left
ventricular systolic dysfunction and right bundle branch block: a systematic review. Heart
Rhythm. Jul 2011;8(7):1083-1087. PMID 21300176
21. Tu R, Zhong G, Zeng Z, et al. Cardiac resynchronization therapy in patients with mild heart
failure: a systematic review and meta-analysis of randomized controlled trials. Cardiovasc
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22. Wells G, Parkash R, Healey JS, et al. Cardiac resynchronization therapy: a meta-analysis of
randomized controlled trials. CMAJ. Mar 8 2011;183(4):421-429. PMID 21282316
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cardioverter-defibrillators and cardiac resynchronization therapy devices: a systematic
review of randomized clinical trials. J Am Coll Cardiol. Aug 30 2011;58(10):995-1000.
PMID 21867832
25. Yu CM, Abraham WT, Bax J, et al. Predictors of response to cardiac resynchronization
therapy (PROSPECT)--study design. Am Heart J. Apr 2005;149(4):600-605. PMID
15990740
26. Chung ES, Leon AR, Tavazzi L, et al. Results of the Predictors of Response to CRT
(PROSPECT) trial. Circulation. May 20 2008;117(20):2608-2616. PMID 18458170
27. Thibault B, Harel F, Ducharme A, et al. Cardiac resynchronization therapy in patients with
heart failure and a qrs complex <120 milliseconds: the evaluation of resynchronization
therapy for heart failure (LESSER-EARTH) Trial. Circulation. Feb 26 2013;127(8):873-881.
PMID 23388213
28. Zusterzeel R, Selzman KA, Sanders WE, et al. Cardiac resynchronization therapy in women:
US Food and Drug Administration meta-analysis of patient-level data. JAMA Intern Med.
Aug 2014;174(8):1340-1348. PMID 25090172
29. Sipahi I, Carrigan TP, Rowland DY, et al. Impact of QRS duration on clinical event
reduction with cardiac resynchronization therapy: meta-analysis of randomized controlled
trials. Arch Intern Med. Sep 12 2011;171(16):1454-1462. PMID 21670335
30. Bryant AR, Wilton SB, Lai MP, et al. Association between QRS duration and outcome with
cardiac resynchronization therapy: a systematic review and meta-analysis. J Electrocardiol.
Mar-Apr 2013;46(2):147-155. PMID 23394690
Page 36
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
31. Stavrakis S, Lazzara R, Thadani U. The benefit of cardiac resynchronization therapy and
QRS duration: a meta-analysis. J Cardiovasc Electrophysiol. Feb 2012;23(2):163-168.
PMID 21815961
32. Sipahi I, Chou JC, Hyden M, et al. Effect of QRS morphology on clinical event reduction
with cardiac resynchronization therapy: meta-analysis of randomized controlled trials. Am
Heart J. Feb 2012;163(2):260-267 e263. PMID 22305845
33. Kang SH, Oh IY, Kang DY, et al. Cardiac resynchronization therapy and QRS duration:
systematic review, meta-analysis, and meta-regression. J Korean Med Sci. Jan
2015;30(1):24-33. PMID 25552880
34. Shah RM, Patel D, Molnar J, et al. Cardiac-resynchronization therapy in patients with
systolic heart failure and QRS interval </=130 ms: insights from a meta-analysis. Europace.
Feb 2015;17(2):267-273. PMID 25164431
35. Peterson PN, Greiner MA, Qualls LG, et al. QRS duration, bundle-branch block
morphology, and outcomes among older patients with heart failure receiving cardiac
resynchronization therapy. JAMA. Aug 14 2013;310(6):617-626. PMID 23942680
36. Kutyifa V, Stockburger M, Daubert JP, et al. PR interval identifies clinical response in
patients with non-left bundle branch block: a multicenter automatic defibrillator
implantation trial-cardiac resynchronization therapy substudy. Circ Arrhythm
Electrophysiol. Aug 2014;7(4):645-651. PMID 24963007
37. Hawkins NM, Petrie MC, MacDonald MR, et al. Selecting patients for cardiac
resynchronization therapy: electrical or mechanical dyssynchrony? Eur Heart J. Jun
2006;27(11):1270-1281. PMID 16527827
38. Diab IG, Hunter RJ, Kamdar R, et al. Does ventricular dyssynchrony on echocardiography
predict response to cardiac resynchronisation therapy? A randomised controlled study.
Heart. Sep 2011;97(17):1410-1416. PMID 21700757
39. Muto C, Solimene F, Gallo P, et al. A randomized study of cardiac resynchronization therapy
defibrillator versus dual-chamber implantable cardioverter-defibrillator in ischemic
cardiomyopathy with narrow QRS: the NARROW-CRT study. Circ Arrhythm Electrophysiol.
Jun 2013;6(3):538-545. PMID 23592833
40. Ruschitzka F, Abraham WT, Singh JP, et al. Cardiac-resynchronization therapy in heart
failure with a narrow QRS complex. N Engl J Med. Oct 10 2013;369(15):1395-1405. PMID
23998714
41. Beshai JF, Grimm RA, Nagueh SF, et al. Cardiac-resynchronization therapy in heart failure
with narrow QRS complexes. N Engl J Med. Dec 13 2007;357(24):2461-2471. PMID
17986493
42. Brignole M, Botto G, Mont L, et al. Cardiac resynchronization therapy in patients
undergoing atrioventricular junction ablation for permanent atrial fibrillation: a randomized
trial. Eur Heart J. Oct 2011;32(19):2420-2429. PMID 21606084
Page 37
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
43. Healey JS, Hohnloser SH, Exner DV, et al. Cardiac resynchronization therapy in patients
with permanent atrial fibrillation: results from the Resynchronization for Ambulatory Heart
Failure Trial (RAFT). Circ Heart Fail. Sep 1 2012;5(5):566-570. PMID 22896584
44. Wilton SB, Leung AA, Ghali WA, et al. Outcomes of cardiac resynchronization therapy in
patients with versus those without atrial fibrillation: a systematic review and meta-analysis.
Heart Rhythm. Jul 2011;8(7):1088-1094. PMID 21338711
45. Ganesan AN, Brooks AG, Roberts-Thomson KC, et al. Role of AV nodal ablation in cardiac
resynchronization in patients with coexistent atrial fibrillation and heart failure a systematic
review. J Am Coll Cardiol. Feb 21 2012;59(8):719-726. PMID 22340263
46. Yin J, Hu H, Wang Y, et al. Effects of atrioventricular nodal ablation on permanent atrial
fibrillation patients with cardiac resynchronization therapy: a systematic review and metaanalysis. Clin Cardiol. Nov 2014;37(11):707-715. PMID 25156448
47. Curtis AB, Worley SJ, Adamson PB, et al. Biventricular pacing for atrioventricular block
and systolic dysfunction. N Engl J Med. Apr 25 2013;368(17):1585-1593. PMID 23614585
48. Yu CM, Chan JY, Zhang Q, et al. Biventricular pacing in patients with bradycardia and
normal ejection fraction. N Engl J Med. Nov 26 2009;361(22):2123-2134. PMID 19915220
49. Chan JY, Fang F, Zhang Q, et al. Biventricular pacing is superior to right ventricular pacing
in bradycardia patients with preserved systolic function: 2-year results of the PACE trial.
Eur Heart J. Oct 2011;32(20):2533-2540. PMID 21875860
50. Yu CM, Fang F, Luo XX, et al. Long-term follow-up results of the pacing to avoid cardiac
enlargement (PACE) trial. Eur J Heart Fail. Sep 2014;16(9):1016-1025. PMID 25179592
51. Doshi RN, Daoud EG, Fellows C, et al. Left ventricular-based cardiac stimulation post AV
nodal ablation evaluation (the PAVE study). J Cardiovasc Electrophysiol. Nov
2005;16(11):1160-1165. PMID 16302897
52. Kindermann M, Hennen B, Jung J, et al. Biventricular versus conventional right ventricular
stimulation for patients with standard pacing indication and left ventricular dysfunction: the
Homburg Biventricular Pacing Evaluation (HOBIPACE). J Am Coll Cardiol. May 16
2006;47(10):1927-1937. PMID 16697307
53. Martinelli Filho M, de Siqueira SF, Costa R, et al. Conventional versus biventricular pacing
in heart failure and bradyarrhythmia: the COMBAT study. J Card Fail. Apr 2010;16(4):293300. PMID 20350695
54. Anselme F, Bordachar P, Pasquie JL, et al. Safety, feasibility, and outcome results of cardiac
resynchronization with triple-site ventricular stimulation compared to conventional cardiac
resynchronization. Heart Rhythm. Jan 2016;13(1):183-189. PMID 26325531
55. Bencardino G, Di Monaco A, Russo E, et al. Outcome of patients treated by cardiac
resynchronization therapy using a quadripolar left ventricular lead. Circ J. Feb 25
2016;80(3):613-618. PMID 26821688
56. Lenarczyk R, Kowalski O, Sredniawa B, et al. Implantation feasibility, procedure-related
adverse events and lead performance during 1-year follow-up in patients undergoing triple-
Page 38
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
site cardiac resynchronization therapy: a substudy of TRUST CRT randomized trial. J
Cardiovasc Electrophysiol. Nov 2012;23(11):1228-1236. PMID 22651239
57. Pappone C, Calovic Z, Vicedomini G, et al. Improving cardiac resynchronization therapy
response with multipoint left ventricular pacing: Twelve-month follow-up study. Heart
Rhythm. Jun 2015;12(6):1250-1258. PMID 25678057
58. Rogers DP, Lambiase PD, Lowe MD, et al. A randomized double-blind crossover trial of
triventricular versus biventricular pacing in heart failure. Eur J Heart Fail. May
2012;14(5):495-505. PMID 22312038
59. Ogano M, Iwasaki YK, Tanabe J, et al. Antiarrhythmic effect of cardiac resynchronization
therapy with triple-site biventricular stimulation. Europace. Oct 2013;15(10):1491-1498.
PMID 23696627
60. Domenichini G, Rahneva T, Diab IG, et al. The lung impedance monitoring in treatment of
chronic heart failure (the LIMIT-CHF study). Europace. Mar 2016;18(3):428-435. PMID
26683599
61. Luthje L, Vollmann D, Seegers J, et al. A randomized study of remote monitoring and fluid
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MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
68. Sekiguchi Y, Tada H, Yoshida K, et al. Significant increase in the incidence of ventricular
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American College of Cardiology Foundation/American Heart Association Task Force on
Practice Guidelines and the Heart Rhythm Society. [corrected]. Circulation. Oct 2
2012;126(14):1784-1800. PMID 22965336
72. European Society of Cardiology, European Heart Rhythm Association, Brignole M, 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. Aug 2013;15(8):1070-1118. PMID 23801827
73. Heart Failure Society of America, Lindenfeld J, Albert NM, et al. HFSA 2010
Comprehensive Heart Failure Practice Guideline. J Card Fail. Jun 2010;16(6):e1-194.
PMID 20610207
IMIT-CHF study). Europace. Mar 2016;18(3):428-435. PMID 26683599
Other Sources:
CMS Centers for Medicare and Medicaid Services (CMS) National Coverage Determination
(NCD) 20.8.3 Cardiac Pacemakers: Single Chamber and Dual Chamber Permanent Cardiac
Pacemakers. Effective 8/13/13 CMS [Website]: www.CMS.gov Accessed August 26, 2016..
Novitas Solutions. Local Coverage Article (LCA) A54982 Single Chamber and Dual Chamber
Permanent Pacemakers – Coding and Billing. Effective 5/1/16. [Website]:
https://www.cms.gov/medicare-coverage-database/details/articledetails.aspx?articleId=54982&ver=6&LCDId=35070&name=314*1&UpdatePeriod=672
&bc=AQAAEAAAAAAAAA%3d%3d&. Accessed August 26, 2016.
Page 40
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
X. POLICY HISTORY
TOP
MP 2.007 CAC 12/2/03
CAC 1/27/04
CAC 10/26/04
CAC 6/28/05
CAC 3/28/06
CAC 3/27/07
CAC 5/27/08
CAC 3/31/09 Consensus
CAC 3/30/10 Minor revision. Statement added that Biventricular pacemakers with or
without an accompanying implantable cardiac defibrillator are considered investigational
as a treatment of NYHA class I or II heart failure.
CAC 11/22/11 Minor revision. Biventricular pacemakers now considered medically
necessary for NYHA class II indications, remaining investigational for class I. The term
“congestive” in reference to the use of biventricular pacemakers was removed.
CAC 10/30/12 BCBSA criteria adopted for biventricular pacemakers. For this
review, a new investigational indication was added for the use of biventricular
pacemakers for the treatment for heart failure in patients with atrial fibrillation.
Policy title revised to “Biventricular Pacemakers (Cardiac Resynchronization
Therapy) for the Treatment of Heart Failure”. The indication as a treatment for
heart failure in patients with atrial fibrillation is considered investigational unless
through medications or ablation, the patient would be expected to be pacemaker
dependent was added to the policy. Rationale for this use of CRT in patients with
atrial fibrillation were also added to the policy background. Criteria for temporary
and permanent pacemakers and cardiac pacemaker monitoring removed from the
policy. FEP variation revised for biventricular pacemakers to refer to the FEP
policy. Codes reviewed 9/18/12.
CAC 11/26/13 Additional investigational policy statement added for triple-site
(triventricular) CRT. Added Rationale section. All rationale information now
contained in that section. Deleted Medicare variation addressing NCD 220.2
Magnetic Resonance Imaging and L30529 - Cardiac Rhythm Device Evaluation.
The CBC policy does not address services described within these documents.
Added reference to NCD 20.8.3 in Medicare variation.
CAC 11/25/14 Consensus review. References and rationale updated. No changes
to the policy statements. Coding reviewed, no changes.
CAC 11/24/15. Minor review. For NYHA Class II, III or IV - changed criteria
from “QRS duration of  (greater than or equal to) 120-130 msec” to “Either left
bundle branch block or QRS duration ≥150 ms” Also changed "Patients treated
with a stable and maximal pharmacological medical regimen prior to implant, such
Page 41
MEDICAL POLICY
POLICY TITLE
BIVENTRICULAR PACEMAKERS (CARDIAC RESYNCHRONIZATION
THERAPY) FOR THE TREATMENT OF HEART FAILURE
POLICY NUMBER
MP-2.007
as an angiotensin converting enzyme (ACE) inhibitor (or an angiotensin receptor
blocker) and a beta blocker, digoxin, and/or diuretics" to "Patients treated with
guideline-directed medical therapy. Link added to 2013 American College of
Cardiology Foundation/American Heart Association guidelines for the management
of heart failure. Policy statement added that CRT in patients with heart failure and
AV block may be considered medically necessary with criteria. Rationale and
references updated. Coding updated.
5/1/16 Administrative change. Added Medicare variation to reference LCA
A54982 Single Chamber and Dual Chamber Permanent Cardiac Pacemakers –
Coding and Billing
Admin update 1/1/17: Product variation section reformatted.
CAC 11/29/16 Minor review. Removed the following statement. The use of
pacemakers or pacemaker monitoring for conditions other than those described in
the policy section is considered investigational. Added the following statement.
The use of biventricular pacemakers (cardiac resynchronization therapy) for
treatment of heart failure in situations other than those described in the policy
section are considered investigational. For NYHA Class III or IV changed QRS
duration from 150 to 120 ms. Updated rationale and references. Coding reviewed.
Top
Health care benefit programs issued or administered by Capital BlueCross and/or its subsidiaries,
Capital Advantage Insurance Company®, Capital Advantage Assurance Company® and Keystone Health
Plan® Central. Independent licensees of the BlueCross BlueShield Association. Communications issued
by Capital BlueCross in its capacity as administrator of programs and provider relations for all
companies.
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