Running Head: CARDIAC RESYNCHRONIZATION THERAPY

Benefits of Cardiac Resynchronization Therapy in Patients with Heart Failure

Research Proposal

Bree Doran

NURS 7002 Nursing Science and Research II

Youngstown State University

Dr. Valerie O’Dell

November 17, 2020

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Abstract

Heart failure effects millions of Americans and places a large burden on healthcare costs

annually. Adequately managing heart failure through device implantation of a cardiac

resynchronization device and appropriate use of guideline medical therapy recommended for

heart failure, heart failure symptoms, quality of life, and cardiac function can be improved. This

study aims to evaluate how appropriate prescribing of guideline medical therapy drugs after the

implantation of a cardiac resynchronization device effects heart failure symptoms as well as their

quality of life. A total of 50 compensated heart failure patients were randomly selected then

divided into groups depending on device implantation and medication prescribed. Group A had a

cardiac resynchronization device and documented prescription guideline medical therapy. Group

B had a cardiac resynchronization device with a lack of appropriately prescribed medications.

Both groups are instructed to keep a medication compliance log until end of study. Participants

are required to meet on a regular basis to complete a questionnaire to evaluate heart failure

symptoms. After study completion the data will be reviewed to see if there is any significant

correlation between cardiac resynchronization device and guideline medical therapy in

improving heart failure symptoms as well as their quality of life.

Keywords: Cardiac resynchronization device, guideline medical therapy, cardiac

function, heart failure

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Chapter 1

Benefits of Cardiac Resynchronization Therapy in Patients with Heart Failure

Heart failure is the leading cause of hospitalizations in patients older than age 65

and nearly 6 million Americans are affected by heart failure (Beckerman, 2018). Improvement in

the treatment and management of heart failure is significant in advanced practice nursing

because inadequate management and recurrent admissions has posed a significant burden. Heart

failure (HF) hospitalizations and readmissions are a financial burden for healthcare across the

globe. It is estimated that HF represents 2% of the total health care expenditure. Recurrent

hospitalizations, pharmacologic treatment to device implantation in combination with HF being

the end point of almost all cardiovascular disease over time is the result of the enormous

financial burden that is presented. In the US, it was estimated in 2012 that HF cost $30.7 billion.

There is a predicted 3-fold increase in 2030, resulting in a $160 billion annual cost (Benjamin,

Muntar, Alonso, Bittencourt, Callaway, Carson, et al, 2019).

Continued research on heart failure treatment and effective outpatient management of

care will help decrease the financial burden by decrease hospital admissions as the number of

patients with heart failure increases over the next decade. A decrease in heart failure

hospitalizations can be achieved through continual medical and pharmacology research.

Research is essential in formulating optimal treatment plans for patients with various levels of

heart failure. The results of research lay the groundwork for medication guidelines and heart

failure treatment protocols. Therefore, the effect of cardiac resynchronization device alongside

guideline directed medical treatment for heart failure will be explored.

Problem Statement
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The problem being addressed is the lack of knowledge surrounding the use of guideline

medical therapy in conjunction with an implanted cardiac resynchronization device to help

improve patient outcomes and quality of life such as activity tolerance, edema, mortality and

hospitalizations. Though these two approaches to heart failure have been utilized for many years,

heart failure admissions with these treatments without one another continue to steadily rise and

costs to healthcare rapidly increase. Can the use of the two treatments together greatly improve

those suffering with heart failure live a longer and more enjoyable life with less hospitalizations?

Purpose of the Study

The purpose of this study is to evaluate how the implantation of a cardiac

resynchronization therapy device in addition to guideline-directed medical therapy effects the

overall life in those with heart failure, specifically: decreasing mortality, increasing left

ventricular ejection fraction and delaying disease progression with an improvement in New York

Heart Association Functional Classification. If there is an improvement in the treatment and

outcomes of heart failure patients using a cardiac resynchronization device, there can be a great

decrease in hospitalizations or rehospitalizations in heart failure patients.

Significance in Nursing

Improvement in the treatment and management of heart failure is significant in advanced

practice nursing because inadequate management and recurrent admissions has posed a

significant burden. Heart failure (HF) hospitalizations and readmissions are a financial burden

for healthcare across the globe. It is estimated that HF represents 2% of the total health care

expenditure. Recurrent hospitalizations, pharmacologic treatment to device implantation in

combination with HF being the end point of almost all cardiovascular disease over time is the

result of the enormous financial burden that is presented. In the US, it was estimated in 2012 that
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CARDIAC RESYNCHRONIZATION THERAPY
HF cost $30.7 billion. There is a predicted 3-fold increase in 2030, resulting in a $160 billion

annual cost (Benjamin, Muntar, Alonso, Bittencourt, Callaway, Carson, et al, 2019). Continued

research on heart failure treatment and effective outpatient management of care will help

decrease the financial burden by decrease hospital admissions as the number of patients with

heart failure increases over the next decade.

Research Question

The purpose of the study was met by answering the following research question:

RQ: In heart failure patients, how does the implantation of a cardiac resynchronization therapy

device with guideline-directed medical therapy compared to guideline-directed medical therapy

alone affect cardiac function within 2 years?

Chapter II

Background

Heart failure is a chronic, progressive illness that is characterized by a decreased function

of the hearts ability to pump adequately to meet the body’s blood and oxygen demand. It is

classified into two groups: Left-sided heart failure and Right-sided heart failure. In left-sided

heart failure, there are two types. The first left sided heart failure is heart failure with reduced

ejection fraction (HFrEF) or systolic heart failure. HFrEF occurs when the left ventricle loses the

ability to pump blood out of the heart into circulation, the heart lacks the strength to pump

adequately. The second left sided heart failure is heart failure with preserved ejection fraction

(HFpEF) or diastolic heart failure. HFpEF occurs when the heart muscle is unable to relax which

causes the ventricles to be inadequately filled, usually caused by a stiffening of the heart muscle.

Right-sided heart failure on the other hand is most commonly a result of left-sided heart failure

in the setting that when the left ventricle begins to fail, the pressure that is created by the
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decreased function of the left ventricle exerts the pressure back to the right side of the heart

resulting in a failure of the right ventricle (American Heart Association, 2020). Heart failure is

classified using the New York Heart Association (NYHA) Functional Classification scale which

helps understand where a patient stands in terms of symptoms. There are two parts to the

classification, functional and observational classifications.

The New York Heart Association functional capacity of patient symptoms is ranked I-IV.

Class I: the patient exhibits no limitation in physical activity, ordinary activity does not cause

unwarranted fatigue, palpitation, or dyspnea. Class II: the patient has slight limitation of physical

activity, comfortable at rest, ordinary physical activity results in fatigue, palpitation, or dyspnea.

Class III: patient has marked limitation or physical activity, comfortable at rest, less than

ordinary activity results in fatigue, palpitation, or dyspnea. Class IV: patient is unable to carry on

any physical activity without discomfort, symptoms of heart failure at rest, if physical activity is

performed, discomfort worsens. The classification is then broken down into objective

assessments ranked A-D. Class A: no objective evidence of cardiovascular disease, no

symptoms, and no limitations in ordinary physical activity. Class B: objective evidence of mild

cardiovascular disease, mild symptoms. and slight limitation of ordinary physical activity,

comfortable at rest. Class C: objective evidence of moderately severe cardiovascular disease,

marked limitation in ordinary physical activity, even during less than ordinary activity, only

comfortable at rest. Class D: objective evidence of severe cardiovascular disease, severe

limitations in physical activity, still experiences symptoms at rest (American Heart Association,

2020). Pharmacologic treatment and lifestyle modification are essential in improving quality of

life in heart failure patients as well as help decrease symptoms associated with heart failure.

While guideline directed medical therapy has been put in place for decades and is always
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changing for heart failure patients, how can further adjustments in management greatly benefit

theses patients? Can device implantation greatly benefit these individuals?

Literature Review

Introduction

The literature for this study will be reviewed in the sequence of how electrocardiography

can accurately help evaluate the contractility and function of the heart, cardiac resynchronization

improvement of left ventricular ejection fraction, decrease in mortality and hospitalizations

followed by the differences between devices of just a cardiac resynchronization device

pacemaker compared to defibrillator. The databases EBSCO, ProQuest, Ohio Link Electric

Journals and CINAHL were searched. Overall, 12 articles and resources were reviewed. The

studies included case studies, cohort design and experimental design. These studies revealed how

heart failure is accurately measured, different variations in heart failure, and how guideline

directed medical therapy or the implantation of a cardiac resynchronization device effect patient

outcomes including mortality. Though all this information is extremely helpful in treating heart

failure patients, there is still little knowledge behind the use of cardiac resynchronization along

with guideline medical therapy to improve outcomes in the long term.

Electrocardiography and Heart Failure Evaluation

In 2016, 736 patients participated in a study approved by Union Hospital, Tongji

Medical College and Huazhong University of Science and Technology in China. In the test

group there were 348 randomized subjects that were diagnosed with congestive heart failure. The

patients were all either diagnosed with hypertensive cardiomyopathy, ischemic cardiomyopathy,

or dilated cardiomyopathy with left ventricular ejection fraction (LVEF) ≤45%. Inclusion criteria

included appropriate LVEF, a New York Heart Association functional class of III or IV despite
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guideline directed medical therapy. If a subject had an MI within the last three months,

pulmonary heart disease, acute heart failure or chronic liver or kidney dysfunction, they were

excluded from the study. In the control group, 388 healthy volunteer subjects were examined

who had no prior history of cardiovascular disease in normal sinus rhythm (Qin et al., n.d.).

All subjects had a transthoracic echocardiography to examine cardiac structure and

function as well as chamber size. The images received from the echocardiography were used to

evaluate LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV) and the LVEF

was then calculated. The mitral valve was then examined to calculate the filling time ratio

(FT/RR) by observing the mitral valve inflow pattern. The FT/RR helped identify any significant

dyssynchrony and there was pre-determined cut-off of ≥40% to indicate significant

dyssynchrony. To further investigate the presence of dyssynchrony, the LV pre-ejection delay

(PED) was identified as the interval from the onset of QRS complex to the onset of LV ejection

velocity, which was compared to the right ventricular ejection velocity to determine the

intraventricular mechanical delay (IVMD). The subject was considered to have significant

dyssynchrony if their calculated IVMD was ≥ 40 milliseconds (Qin et al., n.d.)

Once all calculations to evaluate any discoordination within the heart function, statistical

analyses were performed using SPSS 13.0. When comparing results from the test group and

control group, the test group or CHF group, showed statistically significant (P<0.01) decrease in

LVEF and FT/RR ratios where there was a statistically significant increase in QRS duration,

IVMD, LVEDV and LVESV (P<0.01). The results revealed that the RR/FT ratio decreased

through the groups from LVEF-1 to LVEF-2 to LVEF-3 while the PED and IVMD increased in

the same sequence. This showed that as the RR/FT decreases over the subgroups, the LVEF
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would significantly decrease thus decreasing the function of the heart and increasing the delay

within the ventricles as evidenced by the increasing IVMD (Qin et al., n.d.)

The study shows that echocardiography can be immensely helpful in determining the

severity of cardiac dyssynchrony to better formulate a treatment plan. Understanding the severity

can help determine if the insertion of a cardiac resynchronization therapy device will help

improve LVEF, this improving the pumping ability of the heart. “Echocardiography has a unique

role in the evaluation of cardiac mechanical movement, as synchronization measures may serve

as effective indicators for CRT” (Qin et al., n.d.)Echocardiography can also help patients make

informed and educated decision on treatment plan and device implantation. The overall goal is to

decrease hospitalizations for heart failure patients and increase quality of life.

Device Implantation Effect on Mortality and Hospitalization

In the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure

(COMPANION) trial, there were 1520 patients diagnosed with advanced heart failure assigned

to three groups. Groups were assigned as optimal pharmacological therapy (OPT), optimal

pharmacological therapy plus CRT-P or optimal pharmacological therapy plus CRT-D. The

COMPANION trial was the first cardiac resynchronization therapy-heart failure mortality and

morbidity controlled clinical trial. Risk of hospitalizations and mortality were assessed between

the groups. During the study, 78 patients (25%) were switched to receive CRT due to worsening

heart failure and an increase in hospitalizations related to heart failure (Anand et al., 2009).

Among the total patient population, there were 959 patients were hospitalized at least

once for any cause with a total of 2428 hospitalizations, 66% were admissions for cardiac causes.

When further assessing the cardiac cause hospitalizations, the hospitalizations caused by heart

failure were higher in those receiving only OPT at 46%, compared to CRT-P at 33% and CRT-D
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at 36%. The implantation of CRT-P or CRT-D was associated with a significant decrease in heart

failure hospital admissions per patient year at 44% and 41%, respectively. Throughout the trail,

there was lack of data in some groups due to the OPT having a higher incidence of patients not

being able to follow up due to death, concluding that the sickest patients died before crossing

over to CRT to improve outcomes (Anand et al., 2009).

Data was collected from the French National Database to perform an observational cohort

study to analysis how the optimization of medical treatment affected those with an implanted

cardioverter defibrillator device or a cardiac resynchronization device. 378 patients were

reviewed, 135 who had CRT and 243 who had ICD, at 1, 3 and 5 years to assess heart failure

hospitalization and survival rates. Optimal medical treatment (OMT) is classified by the

European Heart Failure and Cardiac Rhythm management guidelines by being prescribed

ACEi/ARB in combination with a BB and MRA. These guidelines are like those in the United

States as well. Data was statistically analyzed using Chi-square and Kruskal-Wallis to compare

the CRT and ICD groups and then the comparison of treatment before and after the implantation

of CRT or ICD was done using Wilcoxon (Massoullié et al., 2018)

When observing OMT prior to CRT or ICD implantation in the 378 patients between

January 2009 and December 2014, 71% of patients were prescribed a BB, 81% prescribed an

ACEi or ARB and only 35% prescribed an MRA. This showed that prior to the implantation of a

device, there were only approximately 26% of the patients receiving optimal medical treatment

for heart failure, thus putting their chance of survival at a serious disadvantage and their risk of

hospitalization higher. While the optimal medical treatment before device implantation was

subpar, there did seem to be an increase in the prescription rate of BB just before implantation

(Massoullié et al., 2018).

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After CRT or ICD implantation, there was an improvement in prescribing OMT by 19%

but the improvement in OMT was transient in the following 6 months and returned to near

baseline before implantation, though originally patients who were insufficiently treated

decreased from 36% to 26%. Nearly half of the patients saw 2 or more changes to their treatment

regimen after device implantation. Survival rate was assessed at 1, 3 and 5 years which was 89%,

78% and 61%, respectively with no difference between ICD or CRT groups. However, there was

a difference in rehospitalizations between the ICD and CRT groups. In the first year, 22% of the

patients with an ICE were hospitalized for heart failure whereas the CRT group was only 19%. It

was observed that those who were undertreated showed higher hospitalization rates related to

heart failure and heart failure complications compared to those who were receiving 2 or more of

the suggested medical treatment (Massoullié et al., 2018). Overall, “total mortality rate would be

reduced by 2% for every 1% increase in the number of patients treated with 3 therapies”

(Massoullié et al., 2018, p. 727).

The implantation of cardiac resynchronization devices can be one of two options, CRT

with defibrillator (CRT-D) or CRT with pacemaker (CRT-P). The differences and advantages of

both on mortality was investigated in 1122 patients at the Semmelweis University Heart and

Vascular Center in Budapest, Hungary. All patients that had devices implanted had NYHA class

II, III, or IV, QRS prolongation and an LVEF ≤35% and were prescribed OMT which included a

BB, ARB or ACEi, diuretics and an MRA. Which device, either CRT-D or CRT-P, that was

implanted was left to the physician’s discretion at the time of implantation with a distribution of

693 CRT-P devices and 429 CRT-D devices (Kutyifa et al., 2014)

After implantation, patients were provided a follow up 1 month after for device follow up

and then every 6 months thereafter. It was determined that patients with ischemic
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cardiomyopathy were more likely to have a CRT-D implanted. At follow-up, there was a

significant improvement in LVEF in both CRT-P and CRT-D groups where non-ischemic

patients had a greater improvement to ischemic patients. Patients also reported a similar

improvement in quality of life between the two groups. At the median follow-up at 28 months,

34% of the patients observed had died of any cause, distributed as 129 patients in the CRT-D

group and 249 patients in the CRT-P group. The higher incidence in the CRT-P group can be

attributed to the ability of the CRT-D to prevent sudden cardiac death (SCD) with defibrillation

(Kutyifa et al., 2014).

At 5 years, the cumulative survival rate was 56% among the total patient population.

Where there is a significant benefit in preventing SCD in patients with ischemic cardiomyopathy

by implanting CRT-D, there is no additional benefits to those with non-ischemic cardiomyopathy

to have the defibrillator portion of a cardiac resynchronization device implanted. CRT-P is more

beneficial for the patient with non-ischemic cardiomyopathy who are at a low risk for sudden

cardiac death with continual monitoring for deadly cardiac arrhythmias (Kutyifa et al., 2014).

Improvement in Heart Failure Classification and Effect on LV Function

In 2016, Bristow et al. further investigated the COMPANION trial for more data and

observed outcomes of the patients and designated groups. As mentioned above, the trial had the

patients divided into three groups, OPT, OPT with CRT-P and OPT with CRT-D. There is

evidence that in 15-20% of patients with HFrEF, there is dyssynchronous LV contraction that is

induced by intraventricular conduction delays that greatly reduces left ventricle systolic function

resulting in an increase in cardiovascular mortality and morbidity. The trial was able to detect a

25% reduction in the primary outcome with approximately 95% power and a 25% reduction in

mortality with approximately 80% power (Bristow et al., 2016).

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The COMPANION trial is the only clinical trial that has compared CRT-P with CRT-D

both receiving optimal medical therapy. This provides insight to the benefits and disadvantages

to each device and a prediction of hospitalization and mortality. CRT-D provides a larger

reduction in all-cause mortality as compared to CRT-P, 36% versus 24%. It is expected that the

differences in mortality between CRT-D and CRT-P is entirely due to the reduction in sudden

cardiac death in those with a defibrillator ability with a cardiac resynchronization device that

cannot happen with CRT-P. Some therapeutic mechanistic insights obtained from this trail

include how CRT is a benefit to patients with advanced heart failure and high NYHA class

(Bristow et al., 2016).

The function of cardiac resynchronization is to initiate biventricular pacing to assist an

electrically and mechanically dyssynchronous left ventricle to improve the systolic function with

no work from the body itself. This, in turn, increases the efficiency of contraction effectively and

helps increase the systolic blood pressure. CRT acts as a positive inotrope on the heart better

than pharmacologic inotropes. Along with angiotensin converting enzyme inhibitors and beta

blockers, CRT works to produce reverse remodeling (Bristow et al., 2016). “LV reverse

remodeling describes the proves by which an injured LV with a dilated spherical phenotype may

return toward a normalization of ventricular structure and function, either spontaneously or in

response to therapeutic interventions. LV reverse remodeling can occur in response to

interventions that mitigate the source of myocardial injury, or that reduce or eliminate the

neurohormonal and/or hemodynamic factors that contribute to the progression of the LV

remodeling process,” (Saraon & Katz, 2015, p. 173). The study shows that there are possibly

synergistic interactions related to the use of beta blockers alongside CRT due to the decrease in
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heart rate inducing higher pacing percentages. Pacing percentages >98.5% shows to be

associated with even greater reduction in mortality over time (Bristow et al., 2016).

85 patients who were scheduled for CRT implantation were assessed for the Reverse

Electrical Remodeling by Cardiac Resynchronization Therapy (REVERSE). After implantation,

the CRT device was then randomly programed to CRT “on” or CRT “off” and their responses

were monitored. Baseline LVEF was obtained and prior to and 12 months after implantation to

determine CRT response and most patients were on optimal medical therapy at the time of

enrollment of the study. 65 of the 85 patients (76%) were CRT responders, which was

determined if they had an NYHA class improvement ≥1 class and no hospitalization for

decompensated heart failure and an absolute increase in LVEF ≥10%. After 12 months of

biventricular pacing, the improvement in LVEF increased to an average of 39.2±11.3% from

27.2±7.6%. There was an improvement in LV function and remodeling (65% vs 40%) and a

NYHA functional class improvement (86% vs 66%) (Sebag et al., 2012).

Researchers continued to select patients who required CRT implantation to be part of the

randomized, double-blind REVERSE trial and were followed post-implant for a maximum of 5

years. At the completion of the study there were 610 patients who were assigned to CRT “on” or

CRT “off” at a 2:1 ratio. CRT “on” was associated with a decrease in mortality with there being

84 deaths in the 610 patients, 75% of those deaths were patients that were programmed to CRT

“off”, though through statistically analysis, this was not statistically significant due to the sample

size. Further investigation on lifetime survival was conducted and it was revealed that the use of

CRT increased the patients’ life expectancy by 30% which was calculated as approximately 2.46

years. In the patients selected to have their CRT device turned off, the life expectancy was only

0.40 years. Researchers also used the values and information obtained to predict the percentage
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of patients expected to be alive after 10 years, comparing those with CRT “on” versus CRT

“off”. 52.5% of the studied patients were expected to be alive after 10 years with the CRT

function on whereas only 29.7% of the patients with CRT “off” were expected to be alive. This

helped further back that the use of cardiac resynchronization helps improve patient outcomes

(Gold et al., 2015).

The effect of CRT “on” versus CRT “off” on slowing disease progression was also

evaluated. The likelihood in a change of NYHA functional class was significantly increased over

time. There was a high incidence of change from a previously documented NYHA class III to II

with some eventually progressing to class I. When comparing CRT-P versus CRT-D within this

study, those equipped with the defibrillator function did not show any further impact on change

in NYHA class. However, there is evidence that a patient that is equipped with CRT-D is

expected to live 2.77 years longer in addition to the already improved life expectancy when

compared to CRT-P. This is attributed to defibrillators in CRT-D devices ability to prevent

sudden cardiac death (SCD) (Gold et al., 2015).

Martin St. John Sutton and colleagues performed a study of 418 patients with diagnosed

HFrEF from the REVERSE trial and updated associated trials. The patients were evaluated every

6 months with assessments of NYHA class symptoms, 6-minute hall walk, echocardiogram and

quality of life for a randomized period from 2 to 5 years. Within the first year, CRT induced

changes in LV volumes thus improving LV function by 4.6 units, then stabilized in the second

year after increasing 1.3 units. In the next years, the LVEF continued to improve from baseline

with each continued follow up. Over 5 years, the average EF increased from 27.2±6.6% from

33.2±12.7% (St. John Sutton et al., 2017).

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Improvement in LVEF related to CRT implantation was supported by echocardiogram

evidence of a decrease in LVESVI, LVEDVI and LV sphericity that supported the increase in

LVEF across the patient population. This showed to be incredibly strong predictor of decreased

hospitalizations because 33.4% of patients that did not have a significant reduction in LVESVI,

LVEDVI and LV sphericity were more frequently hospitalized or resulted in death. At the end of

the study, with an average age of 62.9±10.6 years, 71% of the patients studied showed to have

heart failure symptom improvement related to extensive LV reverse remodeling with a rapid

decrease in LV dilation after the initiation of CRT (St. John Sutton et al., 2017).

A meta-analysis of three double-blind, randomized control trials (REVERSE, MIRACLE

and MIRACLE ICD) was done to analyze predictors of short-term clinical response to the

initiation of cardiac resynchronization therapy. One thousand and ninety-one patients were

reviewed to compare CRT being programmed on or off, 882 patients had CRT programmed on

and 717 patients were the control group with CRT programmed off. Patients were assessed 6

months for current heart failure symptoms, recent hospitalizations and change in NYHA class.

They were categorized into ‘worsened’, ‘improved’ or ‘unchanged’ depending on the results

(Linde et al., 2017).

Among the patients that were in the test CRT on group, there were 16% of the patients

determined to have worsened from baseline, 24% that remained unchanged from baseline and

60% who were determined to have improved from the baseline at the 6-month mark. Those that

had improvement were improved due to NYHA class improvement and symptom improvements.

The control group with CRT off, 26% of the patients were considered to have worsened, 33%

were unchanged from baseline and 41% were improved at the 6-month mark. This showed that

the patients that were assigned to have their cardiac resynchronization device on had
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approximately 20% more patients with improved symptoms as compared to those with CRT off

(Linde et al., 2017).

Most of the patients that were involved in the meta-analysis were receiving guideline

directed medical therapy with highest compliance in the REVERSE study. With a closer look at

the CRT on group, it displayed that CRT benefited most in patients with the lower ejection

fractions and more prolonged QRS duration. Patients with an NYHA class of III or IV, the

relative benefit of CRT on was much higher than those in lower classes but 2.4. The review of

these three studies displays clear, strong evidence that the implantation and use of CRT results in

a symptomatic improvement of NYHA class as well as improved responses to questions

regarding current symptoms and overall wellbeing answered by the patients after 6 months

(Linde et al., 2017).

At Regional Hospital Liberec in the Czech Republic, 315 patients were studied 12

months after device implantation with laboratory work (NT-proBNP) and an echocardiogram to

better evaluate LV remodeling, change in LVEF as well as how these changes can predict future

outcomes. Along with device implantation, many patients were treated with optimal medical

treatment; 96% on beta-blockers, 99% on ACEi or ARBs, 91% on loop diuretics and 89% on

MRAs. After the mean follow up of 4.8±2.1 years, 82 out of 315 patients with CRT implantation

were hospitalized, 26% of those were for heart failure. The NT-proBNP that as obtained at 12-

months, was determined to be a strong independent predictor of clinical outcome but using

multivariate analysis of data that was collected. This allows healthcare providers to better

understand if a patient will adequately respond to the CRT implantation in years to come or if

further intervention is needed to help improve quality of life and increase life expectancy. Strong

evidence from this study reveals that the absence of echocardiography and laboratory values
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after CRT implantation can significantly put the patient at risk for frequent hospitalizations and

ultimately death (Roubicek et al., 2019).

Conclusion

It is evident that the implantation of a cardiac resynchronization device is extremely

beneficial in helping improve heart failure symptoms and improve quality of life while

decreasing hospitalizations but there is a lack of evidence when adding guideline medical

therapy. Healthcare providers should be mindful of medication management in these critically ill

heart failure patients to reduce healthcare costs related to hospitalizations and improve patient

outcomes and compliance. When a patient feels good and feels an improvement in symptoms,

compliance is easier to obtain.

Chapter III

Research Methods

The information conveyed in Chapter Three proceeds in the following order: Design,

Setting, Sample, Variables, Instruments, Procedure, Recruitment, Statistical Plan, and Data

Management.

Design

The study will be conducted using two designs, experimental and descriptive. The

experimental portion of the study will divide patients who have a cardiac resynchronization

device implanted with documented prescribed guideline medical therapy and the other group will

not have a cardiac resynchronization device implanted but is prescribed all necessary guideline

directed medical therapy prescriptions. The descriptive portion will be conducted using the

NYHA Functional Classification symptom scale and Kansas City Cardiomyopathy

Questionnaire (KCCQ). The NYHA scale and Kansa City Cardiomyopathy Questionnaire will
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collect data from research subjects before, and after introducing the intervention, and is suitable

for the study. Participants will also keep a daily log of medications taken and current symptoms

they are experiencing. After six months, patients will have an echocardiogram performed to

evaluate left ventricular ejection fraction.

Setting

The setting to be used for the study will be a field study. Patients will not be required to

do any activities out of the ordinary other than to take prescribed medications. Participants will

be followed at home with frequent check ins regarding medication compliance and cardiac

symptoms. Remaining at home participants will feel more comfortable completing required

study documents.

Sample

The convenience sample consists of patients who have a cardiac resynchronization device

implants who were admitted to the hospital more than twice in the last 90 days with a diagnosis

of CHF. Convenience sampling is used because this sample is easily accessible and inexpensive

(Wood & Ross-Kerr, 2013). This study was also a non-probability sample because not all

patients diagnosed with CHF are participants of the CHF clinics in the local area. Patients

associated with the CHF clinic as well as patients known to the Mercy CHF Nurse will be

evaluated

Sample Size

The planned sample size will be a minimum of 50 participants that meet required

criteria. Participants will be divided into one of two groups: Group A will be patients with CRT

device and all appropriate guideline medical therapy medications prescribed, group B will be

patients with heart failure who are prescribed all necessary guideline directed medical therapy
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medications. Both groups will be instructed to take all medications as prescribed and log

medication compliance.

Subject Criteria

The subject inclusion and exclusion criteria are as follows:

Subject inclusion criteria are:

1. Compensated patients who were recently admitted at least two times (previous 90 days)

for recent decompensated CHF with the following characteristics were included in the

study: dyspnea, lower extremity edema, weakness, and exercise intolerance

2. May or may not implanted cardiac resynchronization device

3. Patients who are currently on diuretics, and/or hypertensive medications were suitable for

study.

4. Patients who are currently prescribed ACEi or ANRi are suitable for study

5. Patients are to be older than 45 years old.

Subject exclusion criteria are:

1. Patients without a cardiac resynchronization device were excluded.

2. Patients with dementia, cerebral vascular disease, severe hepatic disease, or alcoholic

habits, uncompensated diabetes, and chronic kidney disease requiring dialysis were

excluded.

3. Patients were also excluded if they declined to participate, did not follow instructions

regarding medication and compliance or failed to follow up.

4. Patients were also excluded if informed consent was not returned by March 1, 2021, and

if they are less than 45 years old.

Variables
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Variables of Interest

The variables of interest are implantation of a cardiac resynchronization therapy device,

guideline-directed medical therapy, and cardiac function

Theoretical and Operational Definitions

Implantation of Cardiac Resynchronization Therapy Device: This device is a small

battery-operated device that is implanted under the skin of the chest with a lead inserted into

each ventricle of the heart to assist in restoring coordination in contraction of the heart. (Cardiac

Resynchronization Therapy, 2020). The implantation of a CRT device helps restore coordination

of the ventricles to pump blood more efficiently and strengthen the heart over time (Griffin,

2004). This will be operationalized by classifying those with an implanted CRT and those

without an implanted device.

Guideline-Directed Medical Therapy: In general, patients who are diagnosed with heart

failure, they are prescribed a beta-blocker (BB) and any angiotensin converting enzyme inhibitor

(ACEi), angiotensin receptor blocker (ARB), or angiotensin receptor neprilysin inhibitor

(ANRi). As heart failure progresses, the addition of a mineralocorticoid receptor agonist (MRA)

and hydralazine/nitrates as well as a loop diuretic may be indicated. This will be operationalized

by reviewing patient’s medication lists to determine if the patient is revealing appropriate

medication therapy.

Cardiac Function: Cardiac function is defined by degree of function as evidenced by left

ventricular ejection fraction (LVEF) calculated from a transthoracic echocardiogram, heart

failure classification according to the New York Heart Association (NYHA) functional

classification scale, assessment of heart failure symptoms and mortality rate. Clinically, the left

ventricular ejection fraction is the measurement of what percentage of blood that is being
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CARDIAC RESYNCHRONIZATION THERAPY
pumped out of the left ventricle of the heart with each contraction. Normal LVEF to pump

adequately to meet the body’s blood and oxygen demand (American Heart Association, 2020).

Mortality rate is defined as the number of deaths related to current medical condition(s) in a

specific amount of time. Assessment of cardiac function will be operationalized throughout the

study by evaluating LVEF with an echocardiogram, use of the NYHA Functional Classification

symptom scale (Appendix D) and Kansas City Cardiomyopathy Questionnaire (KCCQ-12)

(Appendix C), and by monitoring deaths that have occurred due to cardiac or heart failure

causes.

Procedure

This study will begin by contacting the Mercy Health Congestive Heart Failure (CHF)

Nurse as well as the CHF Clinics in the Tri-County area. If willing to participate in assisting in

researching the proposed topic, a face to face meeting will be set up for each to provide in detail

information regarding plans for the study. Once there is an agreement made regarding the

research study, the CHF nurse and CHF clinics will provide a list of patients meeting criteria of

being admitted to the hospital in last 90 days with CHF symptoms who have an implanted

cardiac resynchronization device that then will be randomly selected for the study according to

the criteria to obtain 50 participants. Once 50 participants have been selected, an information

letter (Appendix A) will be sent to explain what the study is about. Consent form will need to be

signed and returned within 14 days to be an eligible participant. Prepaid envelopes and stamps

will be provided.

After consent has been obtained, all participants will be required to meet either virtually

or in person at the CHF clinic to review what is expected in the study. Patients will be separated

into two groups depending on medication regimen prescribed by practitioner. Group A will be
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CARDIAC RESYNCHRONIZATION THERAPY
patients who have an implanted cardiac resynchronization device and ON guideline medical

therapy for heart failure and Group B will be patients who have an implanted cardiac

resynchronization device with OFF or subtherapeutic guideline medical therapy. Both groups

will be instructed to take all medications as prescribed and to log medication compliance

(Appendix B). Monthly patients will evaluate symptoms related to heart failure using and Kansas

City Cardiomyopathy Questionnaire (KCCQ-12) (Appendix C) and then will be evaluated using

(NYHA) Functional Classification symptom scale (Appendix D). After a trial period of thirty

days is completed, participants will meet in person to turn in medication compliance logs and

answer questionnaires to evaluate heart failure symptoms. After 6 months, patients will be

scheduled to have an echocardiogram performed to evaluate if there is change in left ventricular

ejection fraction.

Recruitment

Subjects will be recruited via mail whose names were obtained from local CHF clinics

and Mercy Health CHF nurse. Eligibility will be determined by the following criteria: Must be

older than 45 years old, have a current diagnosis of CHF, has an implanted cardiac

resynchronization device and has been admitted to the hospital at least twice in the last ninety

days related to CHF exacerbations symptoms. Absence of face-to-face meeting will relinquish

participation in the study. One week prior to the initiation of the study, a licensed RN will meet

face-o-face with the participants to discuss in detail requirements of the study.

Statistical Plan and Data Management

Statistical Plan for Instrument Outcomes

The data analysis plan will be used to place the data collected from medication

compliance logs and surveys from the study into a chart, graph, or table then I would use
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CARDIAC RESYNCHRONIZATION THERAPY
correlational analysis of relationship among the variables. All calculations will be complete

using SPSS statistical software. The statistical plan for this study will be using a multiple

regression sample size calculation based on b value of 0.10, and a value of 0.05. After the data is

collected it will be calculated using a two-tailed t test to identify any differences between group

A and group B. A P<0.05 was assumed statistically significant. All calculations will be complete

using SPSS statistical software.

Instruments

This study will utilize two instruments to help understand how guideline medical therapy

along with a cardiac resynchronization device may greatly benefit patients with diagnosed heart

failure. A medication compliance log and the Kansas City Cardiomyopathy Questionnaire

(KCCQ-12) will be used.

Instrument #1: Medication Compliance Log

All medication compliance log will be provided to participants (Appendix B) prior to the

beginning of the study. This log will be used to document which medications patient is

prescribed and when they are taken daily. Participants will log when a medication is taken to

ensure compliance. Face validity was determined using this instrument. While this instrument

requires truthfulness from participants, it is extremely important in the study to determine

effectiveness of prescribed medications on heart failure symptoms. Interrater reliability was

determined using data from the sample as, this instrument should produce the same results if

each participant is using it the same way.

Instrument #2: Kansas City Cardiomyopathy Questionnaire (KCCQ-12)

The Kansas City Cardiomyopathy Questionnaire (Appendix C) will be used throughout

the study monthly to track patients’ symptoms related to their heart failure. Questionnaires will
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CARDIAC RESYNCHRONIZATION THERAPY
be provided to patients on follow ups for the study. The questionnaire will have twelve

questions pertaining to heart failure and quality of life. Content validity was determined when

using this instrument as known literature supports the questionnaire as a reliable and accurate

source in rating heart failure symptoms. A test-retest will be used by graphing and scatter

plotting the responses from both groups as a (+) .95 good reliability

Protection of Human Subjects

Institutional Review Board (IRB) approval will be sought and obtained at Youngstown

State University. All participants in the study will be voluntary and participants can choose to

withdraw from the study at any time. No external funding for this study will be provided, and no

deception will be used. Some unanticipated problems that might affect the safety of participants

and may affect the integrity of the study are if participants who are prescribed subtherapeutic

guideline medical therapy may experience rapid decompensation of heart failure and worsening

heart failure symptoms leading to hospitalizations. Some inconveniences that may arise with

participants is the daily log of medications taken for monthly evaluation, the compliance of

recording the medication compliance, and having to meet on a monthly basis to complete

questionnaire for 6 months then every six months following for 2 years. When the study is

closed, a completion report will be submitted within 30 days after submission to willing CHF

clinics, Mercy Health CHF Nurse, and all participants as well.

Conclusion and Significance

Through this research, the medical field will gain insight on what treatments optimally

treat heart failure patients therefore preventing recurrent admissions and improving patient

quality of life. If the use of cardiac resynchronization device along with compliance to guideline

medical therapy greatly improves heart failure symptoms as well as improves cardiac function as
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CARDIAC RESYNCHRONIZATION THERAPY
evidenced by LVEF on an echocardiogram, healthcare systems will be able to reduce costs of

hospitalizations. It is evident that there still is a disconnect in treatment of those with heart

failure and change needs to happen. Now is the time to investigate the use of cardiac

resynchronization devices to help restore adequate coordination within the heart while

prescribing adequate medications to promote remodeling and decrease heart failure symptoms.
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CARDIAC RESYNCHRONIZATION THERAPY
References

American Heart Association. (2020). Heart Failure. Retrieved March 13, 2020, from

https://www.heart.org/en/health-topics/heart-failure

Anand, I. S., Carson, P., Galle, E., Song, R., Boehmer, J., Ghali, J. K., Jaski, B., Lindenfeld, J.,

O’Connor, C., Steinberg, J. S., Leigh, J., Yong, P., Kosorok, M. R., Feldman, A. M.,

Demets, D., & Bristow, M. R. (2009). Cardiac resynchronization therapy reduces the risk

of hospitalizations in patients with advanced heart failure results from the comparison of

medical therapy, pacing and defibrillation in heart failure (COMPANION) trial.

Circulation, 119(7), 969–977. https://doi.org/10.1161/CIRCULATIONAHA.108.793273

Beckerman, J. (2018, September 5). Congestive Heart Failure: Symptoms, Causes, Treatment,

Types, Stages. Retrieved January 19, 2020, from https://www.webmd.com/heart-

disease/guide-heart-failure#7

Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al (2019).

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Association. Circulation. 2019;139(10): e56–528.

Cardiac Resynchronization Device (CRT). (2020). Retrieved March 24, 2020, from

https://stanfordhealthcare.org/medical-treatments/c/cardiac-resynchronization-

therapy.html

Ejection Fraction. (2019, April 29). Retrieved September 10, 2020, from

https://my.clevelandclinic.org/health/articles/16950-ejection-fraction

Gold, M. R., Padhiar, A., Mealing, S., Sidhu, M. K., Tsintzos, S. I., & Abraham, W. T. (2015).

Long-Term Extrapolation of Clinical Benefits Among Patients with Mild Heart Failure

Receiving Cardiac Resynchronization Therapy Analysis of the 5-Year Follow-Up from

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the REVERSE Study. In JACC: Heart Failure (Vol. 3).

https://doi.org/10.1016/j.jchf.2015.05.005

Griffin, R. M. (2004, September 30). Implantable Devices for Heart-Failure Treatment.

Retrieved March 25, 2020, from https://www.webmd.com/heart-disease/heart-

failure/features/heart-failure-treatment-by-device#1

Implantable Cardioverter-Defibrillators (ICD). (2020). Retrieved March 24, 2020, from

https://stanfordhealthcare.org/medical-treatments/i/icd.html

Kutyifa, V., Geller, L., Bogyi, P., Zima, E., Aktas, M. K., Ozcan, E. E., Becker, D., Nagy, V. K.,

Kosztin, A., Szilagyi, S., & Merkely, B. (2014). Effect of cardiac resynchronization

therapy with implantable cardioverter defibrillator versus cardiac resynchronization

therapy with pacemaker on mortality in heart failure patients: Results of a high-volume,

single-centre experience. European Journal of Heart Failure, 16(12), 1323–1330.

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Linde, C., Abraham, W. T., Gold, M. R., Daubert, J. C., Tang, A. S. L., Young, J. B., Sherfesee,

L., Hudnall, J. H., Fagan, D. H., & Cleland, J. G. (2017). Predictors of short-term clinical

response to cardiac resynchronization therapy. European Journal of Heart Failure, 19(8),

1056–1063. https://doi.org/10.1002/ejhf.795

Massoullié, G., Chouki, C., Mulliez, A., Rossignol, P., Ploux, S., Pereira, B., Reuillard, A., Jean,

F., Andronache, M., Eschalier, A., Motreff, P., Clerfond, G., Bordachar, P., Authier, N.,

& Eschalier, R. (2018). Effect of optimization of medical treatment on long-term survival

of patients with heart failure after implantable cardioverter defibrillator and cardiac

resynchronization device implantation (from the French National EGB Database).

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American Journal of Cardiology, 121(6), 725–730.

https://doi.org/10.1016/j.amjcard.2017.12.013

Modin, D., Andersen, D. M., & Biering-Sørensen, T. (2018). Echo and heart failure: when do

people need an echo, and when do they need natriuretic peptides?. Echo research and

practice, 5(2), R65–R79. https://doi.org/10.1530/ERP-18-0004

Qin, C., Zhang, L., Zhang, Z.-M., Wang, B., Ye, Z., Wang, Y., Nanda, N. C., & Xie, M.-X.

(2016). Echocardiographic evaluation of cardiac dyssynchrony in patients with

congestive heart failure. J Huazhong Univ Sci Technol［Med Sci］, 36(3), 2016.

https://doi.org/10.1007/s11596-016-1605-8

Roubicek, T., Stros, J., Kucera, P., Nedbal, P., Cerny, J., Polasek, R., & Wichterle, D. (2019).

Combination of left ventricular reverse remodeling and brain natriuretic peptide level at

one year after cardiac resynchronization therapy predicts long-term clinical outcome.

PLoS ONE, 14(7), 1–16. https://doi.org/10.1371/journal.pone.0219966

Saraon, Tajinderpal MD; Katz, Stuart D. MD, MS Reverse Remodeling in Systolic Heart Failure,

Cardiology in Review, 23(4), 173-181. doi: 10.1097/CRD.0000000000000068

Sebag, F. A., Martins, R. P., Defaye, P., Hidden-Lucet, F., Mabo, P., Daubert, J. C., & Leclercq,

C. (2012). Reverse electrical remodeling by cardiac resynchronization therapy:

Prevalence and clinical impact. Journal of Cardiovascular Electrophysiology, 23(11),

1219–1227. https://doi.org/10.1111/j.1540-8167.2012.02376.x

St. John Sutton, M., Linde, C., Gold, M. R., Abraham, W. T., Ghio, S., Cerkvenik, J., & Daubert,

J. C. (2017). Left ventricular architecture, long-term reverse remodeling, and clinical

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Appendix A

Information Letter for Invitation to be in a Research Study

To Whom it may concern:

This letter is an invitation to consider participating in a study I am conducting as part of my

Master’s degree in the Department of Nursing at Youngstown State University under the
supervision of Dr. Valerie O’Dell. I would like to provide you with more information the about
the study and what is required of you if you choose to participate.

For decades heart failure symptoms have negatively impacted patients with congestive heart
failure thus effecting quality of life. From decreased ability to perform daily tasks to frequent
hospitalizations, this study aims to look into how medication therapy by following guideline
medical therapy recommendations after your device implantation of a cardiac resynchronization
device can greatly improve heart failure symptoms, in turn improving quality of life.

Participation in this study is voluntary. It will involve a meeting of approximately 15 minutes in

length to take place at CHF clinic or virtually to review medication compliance and to take a
brief questionnaire regarding current symptoms. You may decline to answer any questions if you
wish. Further, you may decide to withdraw from this study at any time without any negative
consequences. All information you provide is considered completely confidential. Your name
will not appear in any thesis or report resulting from this study. Data collected during this study
will be retained for two years in locked office in my supervisor’s lab. Only researchers
associated with this project will have access. There are no known or anticipated risks to you as a
participant in this study.

If you have any questions regarding this study, or would like additional information to assist you
in reaching a decision about participation, please contact me at (330) -921-8681 or by e-mail at
Badoran@student.ysu.edu.

I would like to assure you that this study has been reviewed and received ethics clearance
through the Research Ethics Review Board at Youngstown State University. I hope that the
results of my study will be of benefit to those organizations directly involved in the study as well
as to the wider research community.

Thank you very much for your time and assistance in this project, I look forward to speaking
with you soon.

Sincerely,

Bree Doran
Student MSN
Nursing
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Appendix B
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Appendix C

Appendix D
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