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Cardiac Resynchronization Therapy
Introduction
Heart failure is one of the major causes of morbidity and mortality worldwide, and it is associated with poor life expectancy, poor quality of life, and a higher economic burden on the healthcare system.[1] Heart failure can result from several causes, but left ventricular (LV) systolic dysfunction is the major cause of heart failure. Over the past 3 decades, advances in the medical management of heart failure cases with reduced ejection fraction (EF) have improved patient survival. Still, the morbidity and mortality related to heart failure have remained elevated.[2]
With an increase in the population's age and advances in treating ischemic heart diseases, the number of patients with heart failure continues to grow, introducing significant challenges to managing cardiac arrhythmia and advanced heart failure.[3] In patients with heart failure with reduced EF, electromechanical dyssynchrony from intraventricular conduction delays leads to hemodynamic inefficiencies, which consequently worsen functional mitral regurgitation and LV remodeling, eventually leading to poor outcomes.[4][5]
In the early 1990s, it was identified that electromechanical dyssynchrony plays a prominent role in heart failure. Pacing devices that stimulate multiple areas of the heart simultaneously could be used to offset this dyssynchrony and conduction delay.[6] In the late 1990s, Auricchio and Kass first described the efficacy of multisite pacing in humans, which led to the development of cardiac resynchronization therapy (CRT), the first use of artificial electrical stimulation for treating heart failure.[7] Since then, CRT has been an important treatment modality for those with heart failure with reduced EF.[8] This review examines the use of implantable pacing devices in heart failure, with a primary focus on biventricular pacing (cardiac resynchronization). Also discussed are the pathophysiology, indications, complications, and clinical significance.
Anatomy and Physiology
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Anatomy and Physiology
Coronary Sinus Anatomy
The optimal placement of an LV lead in a tributary of the coronary sinus is one of the most challenging technical aspects of CRT device implantation. The coronary sinus is the main vein of the greater venous system that runs in the posterior aspect of the atrioventricular (AV) groove.[9] The coronary sinus is formed when the great cardiac vein joins the main posterior lateral vein. Other major tributaries entering the coronary sinus include the inferior LV vein and the middle cardiac vein, which drain the posterior aspect of the LV. The middle cardiac vein is the largest tributary of the coronary sinus, which receives communications from the anterior veins and the septal and inferior walls of both ventricles.[10]
Pathophysiology of Dyssynchrony
Reducing LV systolic function is associated with neurohumoral activation, leading to ventricular remodeling and dilatation.[11] The majority of patients with cardiomyopathy exhibit conduction delays, such as a left bundle branch block (LBBB), which leads to electromechanical dyssynchrony. The resulting contractile dyssynchrony generates regional heterogeneity of myocardial work, with the early stimulated region having reduced load and territories of late activation having higher load.[12] This displacement of blood from early to late and back to early activation sites results in a net decline in ejected stroke volume. This volume shift is significantly more pronounced when the differences in muscle activation are greatest between the early and late contracting zones.[13] Thus, in heart failure, where the underlying function is already compromised, electromechanical dyssynchrony further increases morbidity and mortality.[14] A simultaneous biventricular preexcitation, characteristic of CRT, restores coordinated contraction and improves net systolic performance by augmenting chamber ejection and work.[15]
Indications
CRT Indications
- Class I recommendation for patients with:
- Left ventricular ejection fraction (LVEF) of less than 36%
- Sinus rhythm with LBBB morphology
- QRS duration of >149 ms
- New York Heart Association (NYHA) II, III, or ambulatory IV symptoms on optimal medical therapy
- Acceptable noncardiac health
- Class IIa recommendation in patients with:
- LVEF <36%
- Sinus rhythm with LBBB morphology
- QRS duration of 120 to 149 ms
- NYHA II, III, or ambulatory IV symptoms on optimal medical therapy
- Acceptable noncardiac health
- Class IIa recommendation in patients with:
- LVEF of less than 36%
- Sinus rhythm with a non–LBBB pattern
- QRS duration of >149 ms
- NYHA III, or ambulatory IV symptoms on optimal medical therapy
- Acceptable noncardiac health
- Class IIa recommendation in patients with:
- LVEF of less than or equal to 35%, on optimal medical therapy
- Atrial fibrillation (and requires ventricular pacing)
- Rate control will end up on 100% ventricular pacing
- Acceptable noncardiac health
- Class IIb recommendation in patients with:
- LVEF of less than 36%
- Sinus rhythm with non–LBBB pattern
- QRS duration of 120 to 149 ms
- NYHA III, or ambulatory IV symptoms on optimal medical therapy
- Acceptable noncardiac health
- Class IIb recommendation in patients with:
- LVEF of less than 36%, on optimal medical therapy
- Undergoing a pacing device implantation for other indications
- Anticipated to have >40% ventricular pacing
- Acceptable noncardiac health
- Congenital heart disease
- The use of implantable cardioverter-defibrillators (ICDs) for the primary prevention of sudden cardiac death has increased among individuals with congenital heart disease. Although randomized controlled trials are lacking, results from several observational studies have consistently identified systemic ventricular dysfunction as the strongest predictor of sudden cardiac death or appropriate ICD therapy in this population. These findings suggest that the role of ICDs may warrant expansion in the future, contingent upon further evidence demonstrating clear clinical benefit in patients with congenital heart disease and significant ventricular impairment.[16] However, current recommendations remain unchanged due to the limited data available. Likewise, there is still insufficient evidence to support specific recommendations regarding CRT in this patient group.[17][18]
Contraindications
There are no established absolute contraindications for CRT in appropriately selected patients. Relative contraindications may include:
- Dementia
- Advanced malignancy requiring palliative care
- Chronic disease with a life expectancy of less than 1 year
- Acute decompensated heart failure
- Active infection or sepsis
- Coagulopathy [19]
Equipment
The following equipment is required for implanting a biventricular pacing device:
- Cardiac catheterization laboratory with fluoroscopy and hemodynamic monitors
- Ultrasound machine (for access)
- Needles and sheaths
- Pacing leads and generator
- Device programmer
- Sutures
Personnel
The following personnel are required for biventricular pacing device implantation:
- Cardiac electrophysiologist
- Cardiac catheterization laboratory technician
- Electrophysiology technologist for programming
- Nursing staff for administering medications
- Anesthesiologist
Sometimes, a cardiac surgeon may be required to implant an epicardial LV lead if it is not possible to place it percutaneously.
Preparation
Preparation is similar to other cardiac catheterization procedures, and includes:
- Patients should be adequately assessed for the procedure and counseled in detail about its risks, benefits, and complications.
- Blood tests are performed before checking the coagulation profile, especially if the patient takes anticoagulants.
- The patient fasts for at least 6 hours before the procedure.
- Intravenous cannulas are maintained, and antibiotics with antistaphylococcal coverage are administered as a prophylaxis for implant infection.
- After arriving in the catheterization laboratory, the patient is draped after the access site is cleaned with an antiseptic solution.
- Intravenous sedation is given before the procedure, and local anesthetic agents are given at the site of venous puncture and pocket formation.
Technique or Treatment
Venous Access
Since its introduction in the early 1990s, the CRT device implantation technique has undergone rapid evolution. A limited thoracotomy approach was initially used for epicardial lead placement; however, advances in LV transvenous lead delivery systems have led to the development of an entirely transvenous implantable system.[20] Despite these advances, technical challenges arise when considering the site of approach for implanting 3 leads—right atrial (RA), right ventricular (RV), and LV epicardial. Commonly used venous approaches include subclavian, axillary, and cephalic veins.[21] The cephalic vein is the preferred venous access for lead implantation, followed by the subclavian vein. The subclavian vein can be accessed either by using axillary vein access or intrathoracic access.[22]
Some operators prefer combined cephalic and subclavian vein access to facilitate easy catheter manipulation and coronary sinus cannulation. This technique minimizes lead interaction and the risk of lead dislodgement during sequential lead placement. However, subclavian vein puncture carries a significant risk of pneumothorax, and it may lead to densely fibrotic tracts as the leads pass through the ligamentous tissues between the medial end of the clavicle and the first rib. And this fibrosis can potentially make percutaneous lead extraction impossible.[23][24]
CRT Leads Implantation
In the case of CRT-D (CRT devices combined with defibrillator), 3 long hydrophilic guidewires are placed in the accessed vein (cephalic or subclavian). An 11-French (Fr) sheath is advanced over 1 of the wires to introduce a 9-Fr RV defibrillator lead, followed by slitting the sheath. The RV lead is then positioned at an appropriate site. After RV led positioning, 2 separate sheaths are advanced over each of the 2 retained guidewires. To avoid lead interaction, these sheaths (for the LV and RA) are not slit until all 3 leads are positioned at their appropriate places.[25]
A guide catheter is placed via the sheath into the coronary sinus over a hydrophilic wire or a deflectable catheter for LV lead placement. Coronary sinus venography can be performed via a balloon-tip catheter inserted into the guide catheter. The LV lead is placed in an appropriate tributary of the coronary sinus guided by fluoroscopy. Ultimately, the RA lead is installed. Once the 3 leads are positioned. The sheath is slit, and the RA and RV leads are sutured onto the pectoral muscle. Finally, the guide sheath is slit, followed by slitting the short 9-Fr sheath and suturing the coronary sinus lead onto the pectoral muscle.[26]
In the case of CRT-P (CRT device without defibrillator), 2 long hydrophilic guidewires are placed in the accessed vein. A 9F sheath was advanced over 1 of the guidewires to position an RV pacing lead, followed by slitting the sheath. After positioning the RV lead, 2 separate sheaths are advanced over the 2 guidewires. Then, a guide catheter is placed to facilitate the placement of the LV lead guided by fluoroscopy. The RA lead is then placed via the remaining sheath. Sheaths are slit, and leads are secured by suturing into the pectoral muscle.[27] Leads are then connected to the generator, which is placed in a pocket created in the pectoral region. Successful resynchronization is achieved by placing the LV lead in an appropriate tributary of the coronary sinus, preferably in the proximal third to the middle third of the left ventricle (LV). The LV lead positioned in the apical region is associated with an unfavorable outcome.[28][29]
Difficulties in LV Lead Placement
The inability to cannulate the coronary sinus or a preselected tributary is usually due to the branch's tortuosity. This can be overcome by using multiple angulations to explore the anatomy and advancing the lead coaxially to the wire and the coronary sinus tributary. Different lead sizes and shapes can also be utilized to overcome this technical difficulty. If these maneuvers are not helpful, it may be worthwhile to try double-wiring the branch with a stiff wire to help straighten it.
Lead instability is uncommon but may occur. A lead with a more aggressive curve or active fixation may be used to prevent this. Stenting may also be used to improve lead stability. With this technique, 2 guidewires are placed in the venous branch, with 1 used to advance the pacing lead and the other used for placement of a stent, which is deployed at low pressure to secure the pacing lead.[30][31]
CRT Programming
An individually adapted AV interval is crucial for achieving maximum benefit from resynchronization. Optimized AV interval programming synchronizes atrial and ventricular contraction, maximizes the atrial contribution to LV diastolic filling, and prevents presystolic mitral regurgitation. Interventricular synchrony and LV contraction can be further optimized by adjusting the ventriculoventricular (VV) interval, although the impact of VV optimization on CRT outcome remains under debate. Noninvasive AV and VV interval optimization methods using electro- and echocardiography can be considered, although clinical outcome data do not support their use.[32][33][34]
Complications
Major complications associated with CRT device implantation include the following:
- Access site bleeding and pocket hematoma
- The incidence in clinical trials is reported up to 2.5%.[35] However, in routine clinical practice, the incidence of pocket hematomas may be higher than this, as the trials only reported those hematomas requiring intervention. Pocket hematoma and early reintervention for pocket hematoma are associated with an increased incidence of device infection.
- Lead dislodgement
- Results from CRT trials demonstrated a rate of lead dislodgement from 2.9% to 10%. The incidence of LV lead dislodgement is higher than that of the RA and RV leads.[36]
- Infection
- This is one of the challenging complications related to CRT and other cardiac implantable devices. The incidence of device-related infection for CRT implantation is reported to be up to 3.3%. Male sex, prior device-related infection, and reimplantation are reported to have a higher incidence of device-related infections.[37]
- Pneumothorax
- This is a rare complication, reported in up to 0.66% of cardiac pacing device implantations. Subclavian access, chronic obstructive pulmonary disease, and advanced age (eg, 80 and older) at implantation are reported with a higher pneumothorax incidence. The cephalic vein cut-down technique should be used whenever possible to avoid this complication.[38]
- Coronary sinus perforation/dissection
- Coronary venous dissection is a rare but recognized complication of LV lead placement during the implantation of a CRT device. This complication occurs in up to 0.28% of cases and is reported to prolong postprocedural hospital stays.[38]
Other complications may include cardiac tamponade, myocardial injury, lead fracture, pocket erosion, and phrenic nerve stimulation. Inappropriate phrenic nerve stimulation occurs in up to 13% of patients undergoing LV lead placement and is more common at midlateral, midposterior, and apical sites.[39]
Clinical Significance
With the advancing age of the population and improved survival after ischemic heart disease, the incidence and prevalence of heart failure have risen significantly, making it one of the most common and deadly cardiovascular diagnoses today.[40][41] While medical therapies, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, aldosterone antagonists, and angiotensin receptor neprilysin inhibitors, have improved outcomes for many patients, a substantial proportion still experience progressive symptoms, hospitalizations, and a poor prognosis despite optimal pharmacological treatment.[42][43] To further improve survival, heart failure management must target both sudden cardiac death (the leading cause of death in patients with NYHA Class I–II symptoms) and progressive pump failure (a major cause in NYHA Class III–IV patients).[44]
CRT offers a powerful device-based intervention for select patients with heart failure, particularly those with LV systolic dysfunction and conduction delays such as LBBB, which cause electromechanical dyssynchrony and regional disparities in myocardial workload.[12] CRT improves survival, enhances functional class, quality of life, and exercise capacity (eg, peak volume of oxygen consumption [VO2]), and reduces heart failure–related hospitalizations.[36][45][46][47] The success of CRT hinges on expert procedural execution, including careful preprocedure patient selection based on guideline-recommended criteria, sterile operative technique to minimize device infection, and meticulous LV lead placement—ideally in a proximal or mid-lateral coronary sinus branch, avoiding apical sites that are linked to worse outcomes.[28] After implantation, precise device programming—particularly optimized atrioventricular interval and interventricular interval adjustments—is critical to maximize atrial contribution to LV filling, prevent presystolic mitral regurgitation, and achieve effective resynchronization. Together, these steps ensure that CRT can fully deliver on its potential to transform the lives of patients with advanced heart failure.
Enhancing Healthcare Team Outcomes
Effectively delivering CRT relies on the combined skills, strategies, and coordinated efforts of a multidisciplinary team. Advanced clinicians must accurately identify appropriate candidates, balancing clinical criteria such as reduced ejection fraction and conduction delays with individualized risk-benefit considerations. Electrophysiologists bring specialized procedural skills in lead placement and device programming, while nurses play a crucial role in patient education, perioperative care, and ongoing symptom monitoring. Pharmacists contribute by optimizing medication regimens to complement device therapy, managing heart failure pharmacotherapy, and minimizing drug-device interactions. Dietitians and rehabilitation specialists further enhance outcomes by supporting lifestyle modifications and cardiac rehabilitation efforts tailored to each patient’s needs.
Interprofessional communication and seamless care coordination are crucial for maximizing CRT benefits and ensuring patient safety. Regular multidisciplinary meetings, structured handoffs, and shared electronic health records facilitate clear communication of clinical goals, device settings, and patient progress. Collaborative, interdisciplinary efforts support the timely identification of nonresponders, early management of complications, and individualized adjustments to care plans. Coordination minimizes errors, reduces delays, and enhances patient safety, ultimately leading to improved outcomes and patient-centered care that prioritizes the well-being and satisfaction of patients undergoing CRT.
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