Cardiac Resynchronization Therapy in Heart Failure Management

Heart failure (HF) is a worldwide health problem with high prevalence rate. The prevalence is over 23 million worldwide. It is a chronic disease characterized by the inability of the heart to pump an adequate amount of blood to achieve the demand of the different organ systems and/or doing so at increased filling pressures. Despite many recent advances in medication, the rate of people with HF is rising. This health challenges need to be answered properly. One of the new important treatment for HF is cardiac resynchronization therapy (CRT). Many patients with HF also have an abnormality of the heart’s electrical system resulting in asynchronous contraction pattern of heart muscle. The ultimate goal of CRT is to restore synchrony of the heart rhythm in HF patients. CRT implantation in heart failure patients with proper indications like wide QRS complexes, low left ventricular ejection fraction (LVEF), and left bundle branch block (LBBB) has been proved to reduce morbidity, mortality, and also improve symptoms and quality of life (QoL).


Cardiac Resynchronization Therapy in Heart Failure Management
Hilman Zulkifli Amin, Siska Suridanda Danny Heart failure (HF) is a worldwide health problem with high prevalence rate.The prevalence is over 23 million worldwide.It is a chronic disease characterized by the inability of the heart to pump an adequate amount of blood to achieve the demand of the different organ systems and/or doing so at increased filling pressures.Despite many recent advances in medication, the rate of people with HF is rising.This health challenges need to be answered properly.One of the new important treatment for HF is cardiac resynchronization therapy (CRT).Many patients with HF also have an abnormality of the heart's electrical system resulting in asynchronous contraction pattern of heart muscle.The ultimate goal of CRT is to restore synchrony of the heart rhythm in HF patients.CRT implantation in heart failure patients with proper indications like wide QRS complexes, low left ventricular ejection fraction (LVEF), and left bundle branch block (LBBB) has been proved to reduce morbidity, mortality, and also improve symptoms and quality of life (QoL).
H eart failure (HF) is a chronic disease characterized by the inability of the heart to pump an adequate amount of blood to achieve the demand of the different organ systems and/or doing so at increased filling pressures. 1F caused by the weakening of the heart muscle.It is most commonly caused by irreversible damage from coronary artery disease, but may also be result of viral infections, genetic factors, or toxins. 2 HF is a worldwide health problem with high prevalence rate.The prevalence is over 23 million worldwide. 3This disease carries substantial risk of morbidity and mortality.Over 2.4 million patients are hospitalized and nearly 300,000 deaths annually are directly attributable to HF.There is a dramatic increase in the prevalence of HF.The growing prevalence of HF might reflect increasing incidence, an aging population, improvements in the treatment of acute cardiovascular disease and HF, or combination of these factors.Since then, medications are the mainstay therapy for patients with HF.
Medications help rid the body extra fluid, strengthen the heart's contraction, and ease the heart's workload by relaxing the blood vessels and reducing of this electrical delay on an electrocardiogram (ECG) is widening of the QRS complex.

Cardiac Resynchronization Therapy (CRT)
The ultimate goal of CRT is to restore synchrony of the heart rhythm in HF patients.It is a unique type of cardiac pacemaker. 5Pacemakers usually being used to prevent symptoms associated with symptomatic slow heart rates.The patient's heart rate is continuously monitored by the pacemaker.The heart rate is stimulated by the pacemaker by delivering a tiny electrical charge when necessary. 3Common pacemakers have 2 leads, one in the right atrium and one in the right ventricle, in order to keep the normal pump function relationship between bottom and top of the heart.These leads are connected to a pulse generator placed under the skin in the upper chest.
CRT is a specialized type of pacemakers, that have a third lead which is positioned in a vein on the outer surface of the left ventricle, in addition to the 2 leads used by common pacemakers. 3,5This allows a synchronous pumping action of left and right ventricle.
There are two types of CRT, a CRT pacemaker and a combination CRT pacemaker with defibrillation therapy (CRT-D). 5Both help to coordinate the heart pumping action and improve blood flow.In CRT-D, it also has the ability to detect and treat malignant heart rhythms, which some individuals with a damaged heart muscle may be at risk for developing.The decision of which device to use depends on the physician.the resistance to pumping blood. 3Despite many recent advances in medication, the rate of people with HF is rising.This health challenges need to be answered properly.One of the new important treatment for HF is cardiac resynchronization therapy (CRT).Many patients with HF also have an abnormality of the heart's electrical system resulting in asynchronous contraction pattern of heart muscle.

Heart Electrical System Conduction In Hf
The normal heart rhythm is originated by an electrical signal from a region of the right atrium (RA) known as the sinoatrial or SA node.After that, the electrical signal run through both atria and make them pump blood into the ventricles. 3The atrioventricular node or AV node, then is reached by an electrical signal.The signal then spreads through specialized routes called the left and right bundle branch branches.Finally, the bundle branches stimulate both ventricles to contract synchronously.This electrical system conduction is important for optimal blood pumping to all over body.
The most common abnormality conduction in HF patient is left bundle branch block (LBBB). 3ecause of this block, the right ventricle made an earlier contraction than the left ventricle, instead of simultaneously.The result is an asynchronous contraction of the ventricles.Eventually, cardiac pump will lose its efficiency.Almost 40% of HF patients have an asynchronous ventricular contraction caused by electrical delay, most often LBBB.The appearance

Indications and Benefits of CRT in Heart failure Management
Many conclusive evidences of CRT benefits in HF from several randomized clinical trials (RCTs). 6The inclusion criteria used in the most RCTs was, New York Heart Association (NYHA) functional class III-IV in sinus rhythm (SR), low left ventricular ejection fraction (LVEF) < 35%, and duration of QRS interval > 120 ms.The Cardiac Resynchronization in Heart Failure (CARE-HF) trials with 813 patients evaluated all-cause mortality, hospitalization, NYHA functional class, and quality of life (QoL). 6,7This study was doubleblinded and randomized trial.The result was CRT proved to reduce all-cause mortality, hospitalization, improved NYHA functional class, and QoL.Other study showing similar result was Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial.This study even has larger subjects which was 1520 patients. 6,8The result was also the same that CRT could reduced all-cause mortality or hospitalization.0][11] These studies proved that CRT could improved QoL, NYHA functional class, 6-minutes walk distance (6MWD), LVEF, and peak VO 2 .
However, in accordance to the low number of subjects enrolled in RCTs, the evidence in HF patients with NYHA functional class IV was limited (from 7 to 15%). 6Ambulatory HF patients functional class IV showed a significant reduction in the combined primary endpoint of time to all-cause mortality and hospitalization as shown in a sub-study of COMPANION trial. 6,8The summary of the RCTs of CRT benefit in HF patients with NYHA functional class III-IV, sinus rhythm, poor left ventricular ejection fraction (LVEF), and prolonged QRS interval (>120 ms) will be shown on the table below.
Other topic related to the CRT benefit in HF patients was the impact of QRS duration on the efficacy of CRT.7][8] The effect and benefit of CRT declined with shorter QRS duration.These studies also supported by Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) trial. 6,12It showed that patients with a QRS duration > 150 ms, has a most benefit effect from CRT and suggested that it might not effective in patients with QRS < 150 ms.In addition, most patients in the RCTs had LBBB morphology, which was associated, with a more pronounced benefit, compared with non-LBBB patients.3][14] Patients with complete LBBB, showed a greater benefit on the composite of morbidity and mortality from CRT, compared with patients with non-specific IVCD or RBBB. 6However, patients with LBBB had longer QRS duration, and therefore analyses by morphology may be confounded by QRS duration.On the other hand, the MADIT-CRT trial showed that non-LBBB patients did not derive clinical benefit from CRT (statistically not significant 24% increased risk). 6,12Other trials also showed consistent results that indicated clinical benefit of CRT in LBBB patients. 5ased on this evidence, current class I recommendations were restricted to patients with complete LBBB.The relationship between QRS duration and morphology requires further research.

I B
3][14][15] However, improvement in functional status or quality of life among patients randomized to CRT were not too significant.Most patients enrolled had NYHA functional class II; only 15% in Resynchronization Reverses Remodelling in Systolic Left Ventricular Dysfunction (REVERSE) and 18% in Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) were in NYHA functional class I. CRT did not reduce all-cause mortality of HF events among NYHA functional class I patients.Therefore, the recommendation is restricted to patients in NYHA functional class II.
Finally, there is no evidence of benefit in patients with HF and QRS < 120 ms.In the Cardiac Resynchronization Therapy In Patients with Heart Failure and Narrow QRS (RethinQ) trial, CRT did not improve peak oxygen consumption (primary endpoint) or QoL in the subgroup of patients with QRS < 120 ms and evidence of echocardiography dysscynhrony.

CRT In Heart failure Management With Atrial fibrillation (Af)
There are two ways of considering CRT for AF patients, first, AF patients with moderate to severe HF with a hemodynamic indication for CRT.Second, patients with a fast ventricular rate with HF or LV dysfunction justifying a strong rate control strategy with an AV junction ablation. 6n the first way of considering CRT for AF patients were described in Multisite Stimulation in Cardiomyopathies (MUSTIC) AF trial. 6,18There was a slight but significant improvement in functional status in patients with NYHA functional class III, low LVEF, AF rhythm, and QRS > 120 ms at 6-month and 1-year follow-up.In the Ablate and Pace in AF (APAF) trial, in the patients with low LVEF, NYHA functional class > III, AF rhythm, and QRS > 120 ms, CRT significantly reduced the primary endpoint, including death, hospitalizations or worsening of HF, as well as beneficial effect on LV reverse remodeling. 6,19econd way, combination of AV junction ablation and CRT in uncontrolled heart rate of AF patients provided highly efficient rate control, regularization of the ventricular response, and also improved symptoms. 6Hence, CRT may prevent the potential LV asynchrony.The multi-center, randomized, and prospective APAF trial with 186 patients studied about CRT implantation followed by AV junction ablation. 6,19During a median followup of 20 months, CRT significantly decreased the primary composite endpoint (of death due to HF, hospitalization or worsening due to HF) by 63% in the overall population.The effects and efficacy of CRT were significantly consistent in patients who had EF < 35%, NYHA functional class > III, and QRS width > 120 ms, thus meeting the requirement of the guidelines.

Conclusion
The prevalence of HF is still high.This disease carries substantial risk of morbidity and mortality.Over 2.4 million patients are hospitalized and nearly 300,000 deaths annually are directly attributable to HF. HF is characterized by the inability of the heart to pump an adequate amount of blood to achieve the demand of the different organ systems and/or doing so at increased filling pressures.The most common abnormality conduction in HF patient is left bundle branch block (LBBB).Because of this block, the right ventricle made an earlier contraction than the left ventricle, instead of simultaneously.The result is an asynchronous contraction of the ventricles.Eventually, cardiac pump will lose its efficiency.. Almost 40% of HF patients have an asynchronous ventricular contraction caused by electrical delay, most often LBBB.CRT, a specialized and unique pacemaker, plays an important new role as a novel treatment in HF patients, despite many recent advances in medication.HF patients with proper and right indications like wide QRS complexes, low left ventricular ejection fraction (LVEF), LBBB, SR with conduction delay, and permanent AF have shown improvement of symptoms and QoL.Thus, CRT have been proven to reduce morbidity and mortality in HF patients.Patients should generally not be implanted during admission for acute decompensated HF.In such patients, guideline-indicated medical treatment should be optimized and the patient reviewed as an out-patient after stabilization.It is recognized that this may not always be possible.

Figure 1 .
Figure 1.LBBB and Improvement of Conduction System by CRT 4

Table 1 .
Summary of Randomized Clinical Trials 6 (With permission of Oxford University Press (UK) (c) European Society of Cardiology, www.escardio.org)Evaluating CRT in HF patients and Sinus Rhythm

Table 2 .
Indications for CRT in HF Patients and Sinus Rhythm 6 (With permission of Oxford University Press (UK) (c) European Society of Cardiology, www.escardio.org) 6,16Patients should generally not be implanted during admission for acute decompensated HF.In such patients, guideline-indicated medical treatment should be optimized and the patient reviewed as an out-patient after stabilization.It is recognized that this may not always be possible.
a Class of recommendation.b Level of evidence.c Reference(s) supporting recommendation(s).d

Table 3 .
6ndications for CRT in HF Patients and Atrial Fibrillation6(With permission of Oxford University Press (UK) (c) European Society of Cardiology, www.escardio.org) a Class of recommendation.bLevel of evidence.cReference(s) supporting recommendation(s).d