Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT), also known as biventricular pacing or multisite ventricular pacing, involves simultaneous pacing of the right ventricle (RV) and the left ventricle (LV). In addition to a conventional RV endocardial lead (with or without a right atrial [RA] lead), CRT involves an additional coronary sinus (CS) lead placed for LV pacing. (See Permanent Pacemaker Insertion.)

CRT has made a dramatic impact on the treatment of most patients with heart failure (HF) and an abnormal QRS duration. It was introduced in the 1990s and revolutionized therapy for many patients with persistent symptoms of systolic HF. The basic goal of CRT is to restore LV synchrony in patients with dilated cardiomyopathy and a widened QRS, which is predominantly a result of left bundle branch block, thereby improving mechanical functioning of the LV. (Ie, The aim of CRT is to restore mechanical synchrony by electrically activating the heart in a synchronized manner.) This involves placement of a CS lead for LV pacing, in addition to placement of a conventional RV endocardial lead, with or without a (right atrial) lead.

There is strong evidence from randomized controlled trials showing that CRT combined with optimal medical therapy improves HF symptoms, LV ejection fraction (LVEF), and quality of life (QOL), while decreasing HF hospitalizations and reducing mortality.[2]

The QRS complex on a surface 12-lead electrocardiogram (ECG) represents ventricular depolarization. The QRS duration (QRSd) is the most readily available marker of ventricular dyssynchrony. A prolonged QRS has been shown to be a marker for atrioventricular, interventricular, and intraleft ventricular dyssynchronies.[3] The net result of these disturbances in timing of cardiac contraction is decreased pump function. The American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) and Heart Failure Society of America (HFSA) guidelines recommend use of cardiac resynchronization therapy for a QRS duration longer than 120 ms on the 12-lead ECG as a marker of ventricular dyssynchrony.[4, 5]

Randomized clinical trials have confirmed the effectiveness of cardiac resynchronization therapy (CRT) for the following purposes:

• Improving cardiac hemodynamics and symptoms[6, 7]

• Preventing hospitalization

• Improving mortality[8]  (relative to conventional therapy) in patients with advanced heart failure (HF) symptoms and severe left ventricular (LV) dysfunction

Evidence suggests that CRT may even be beneficial in patients with mildly symptomatic HF (New York Heart Association [NYHA] class II).[8, 9, 10]  A study of 659 patients with HF who underwent successful CRT found the procedure safe to use in patients with clinically significant mitral regurgitation (MR).[11] At 12-month follow-up, patients with more than mild MR had comparable results to patients with mild or no MR. Most of the benefits appear to be associated with the presence of left bundle branch block (LBBB) on electrocardiography (ECG).[11]  The longer the QRS duration (QRSd) (particularly >150 msec), the more beneficial CRT is likely to be.[12]

In light of this and other accumulating evidence, the American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS) modified the class I indication for CRT to include not only patients with NYHA class III and IV symptoms but also those with NYHA class II symptoms and LBBB with a QRSd that is at least 150 ms.[5]

Results from a retrospective study that evaluated long-term outcomes in patients with ambulatory NYHA class III and IV HF who underwent CRT over a 4-year period (2003-2007) indicate that, despite inferior outcomes for those with ambulatory NYHA class IV heart relative to those with NYHA class III symptoms, the survival of patients in both groups are parallel over extended follow-up (mean follow-up, 5.0 ± 2.5 y).[13]  Ambulatory NYHA class IV status was an independent factor for poor long-term outcomes, with a 40% survival free of LV assist device (LVAD) or heart transplantation at 5 years.

The ACC/AHA/HRS guidelines for CRT[4, 5]

Class I (“Indicated”)

CRT is indicated for the following:

• (With or without an implantable cardioverter-defibrillator [ICD]) Patients with sinus rhythm, an LVEF of 35% or less, a QRSd of 120 ms or longer, and an NYHA functional class III or ambulatory IV HF symptoms despite optimal medical therapy ^[4]
• Patients with sinus rhythm, an LVEF of 35% or less, LBBB with a QRSd of at least 150 ms, and NYHA class II, III, or ambulatory IV symptoms despite optimal medical therapy ^[5]

Class IIa (“Reasonable”)

CRT can be useful for patients who have the following conditions[5] :

• An LVEF up to 35%, sinus rhythm, LBBB with a QRSd of 120-149 ms, and NYHA class II, III, or ambulatory IV symptoms on guideline-directed medical therapy (GDMT)
• An LVEF up to 35%, sinus rhythm, a non-LBBB pattern with a QRSd of at least 150 ms, and NYHA class III/ambulatory class IV symptoms on GDMT
• Atrial fibrillation and an LVEF up to 35% on GDMT if a) the patient requires ventricular pacing or otherwise meets CRT criteria and b) atrioventricular (AV) nodal ablation or pharmacologic rate control will allow near 100% ventricular pacing with CRT
• On GDMT, with an LVEF up to 35% and undergoing new or replacement device placement with anticipated requirement for significant (>40%) ventricular pacing

Class IIb (“May be considered”)

CRT may be considered for patients who have the following[5] :

• An LVEF up to 30%, an ischemic HF etiology, sinus rhythm, LBBB with a QRSd of at least 150 ms, and an NYHA class I symptoms on GDMT
• An LVEF up to 35%, sinus rhythm, a non-LBBB pattern with a QRSd of 120-149 ms, and an NYHA class III/ambulatory class IV on GDMT
• An LVEF up to 35%, sinus rhythm, a non-LBBB pattern with a QRSd of at least 150 ms, and NYHA class II symptoms on GDMT

In patients with other forms of conduction disturbance (eg, right bundle branch block [RBBB] or right ventricular [RV] pacing), cardiac resynchronization therapy (CRT) is of questionable utility and therefore cannot be recommended at this time.

American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS) guidelines

Class III ("No benefit")

• CRT is not recommended for patients with NYHA class I or II symptoms and non-LBBB pattern with a QRSd less than 150 ms.
• CRT is not indicated for patients whose comorbidities and/or frailty limit survival with good functional capacity to less than 1 year.

Multiple sheaths are available for obtaining access to the coronary sinus (CS). The various delivery systems differ with regard to shape and especially with regard to size. For example, one delivery system allows the delivery of a 6F pacing lead via the inner catheter, whereas other systems allow delivery of only 4F leads.

Selection of the pacing leads should be dictated predominantly by the anatomy of the branch and the ease of deliverability. Bipolar leads are used in most cases, with unipolar leads reserved for patients with extremely small branches (ie, branches that are too small to accommodate a 4F bipolar lead). In Europe, multipolar leads with four separate pacing electrodes are available; these have been associated with improved implantation success.[14]

Left ventricular (LV) pacing leads are typically secured either with active fixation using tines or with passive fixation using the multiple curves of the lead to fit it tightly in the target vein. An active-fixation unipolar lead is available whose tines can be extended from the body of the lead (proximal to the pacing port) and retracted if repositioning is necessary.

Leads from different manufacturers have not only different fixation curves but also different pacing electrode spacing. Wider pacing electrode placement improves lead capture and electronic repositioning (ie, changing the pacing vector), but it also increases the risk for diaphragmatic capture.

Pacemakers

A pacemaker is an electronic device, approximately the size of a pocket watch, that senses intrinsic heart rhythms and provides electrical stimulation when indicated. Cardiac pacing can be either temporary or permanent.

Permanent pacing is most commonly accomplished through transvenous placement of leads to the endocardium (ie, right atrium [RA] or right ventricle [RV]) or epicardium (ie, to the LV surface via the CS), which are subsequently connected to a pacing generator placed subcutaneously in the infraclavicular region.

Permanent pacemakers are implantable devices that sense intrinsic cardiac electric potentials and, if these are too infrequent or absent, transmit electrical impulses to the heart to stimulate myocardial contraction. A specialized type of pacemaker therapy, cardiac resynchronization therapy (CRT) with biventricular pacing, with or without an implantable cardioverter-defibrillator (ICD), has been used as adjunctive therapy in patients with heart failure.

For more information, see the article Pacemakers and Implantable Cardioverter-Defibrillators.

Implantable Defibrillators

The ICD is first-line treatment and prophylaxis in patients at risk for ventricular tachycardia (VT) or ventricular fibrillation (VF). Available devices offer tiered therapy with programmable antitachycardia pacing schemes, as well as low-energy and high-energy shocks in multiple tachycardia zones.

Dual-chamber, rate-responsive bradycardia pacing is available in all ICDs, and sophisticated discrimination algorithms minimize shocks for atrial fibrillation, sinus tachycardia, and other non–life-threatening supraventricular tachyarrhythmias. Diagnostic functions, including stored electrograms, allow for verification of shock appropriateness.

For more information, see the articles Pacemakers and Implantable Cardioverter-Defibrillators and Cardioverter-Defibrillator Implantation.

Cardiac resynchronization therapy (CRT) has been solidly established as an important advanced heart failure (HF) therapy to reduce all-cause mortality, death resulting from progressive HF, and symptoms of HF, as well as to improve left ventricular (LV) function.[6, 7, 8, 9, 10, 15]

Predictors of response to CRT with an implantable cardioverter-defibrillator (ICD) appear to include a native left bundle branch block (LBBB), nonischemic cardiomyopathy, and femal sex.[16]  Factors contributing to nonresponse to CRT may include patient selection, inadequate delivery and supoptimal lead position.[17]

The Multisite Stimulation in Cardiomyopathy (MUSTIC) trial was one of the first trials to demonstrate significant clinical improvement with CRT.[18]  The investigators included patients with New York Heart Association (NYHA) functional class III HF with an LV ejection fraction (LVEF) of 35% or less, an LV end-diastolic diameter greater than 60 mm, and a QRS duration (QRSd) longer than 150 ms to compare exercise tolerance and quality of life (QOL) during active biventricular pacing for 3 months and during backup right-ventricular (RV)-only pacing for another 3 months. The results showed a statistically significant improvement in 6-minute walking distance (the primary end point), as well as an improved QOL and peak oxygen consumption.[18]

The MUSTIC trial was followed by the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) study, in which 453 patients in sinus rhythm with NYHA class III or IV HF, an LVEF of 35% or less, and a QRSd longer than 130 ms were randomly assigned to CRT versus control.[19]  The patients had significant improvements in 6-minute walking distance, NYHA functional class, and QOL score, as well as the number of hospitalizations secondary to HF.[19] The ensuing MIRACLE Implantable Cardiac Defibrillator (MIRACLE ICD) trial, the first randomized trial to evaluate the effectiveness of CRT with an ICD, showed that after 6 months, there was a statistically significant improvement in the QOL score, peak oxygen consumption, and functional capacity.[7] The results also demonstrated that CRT does not interfere with cardioverter-defibrillator function.

The Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial was the largest and arguably the most important trial to show CRT in combination with optimal pharmacologic therapy, with and without ICD, could significantly reduce mortality and hospitalization in patients with HF.[6] The study comprised 1520 patients with an NYHA class III or IV HF, an LVEF of 35% or less, and a QRSd of 120 ms or longer. Unlike previous trials, COMPANION evaluated a primary composite end point of time to hospitalization or death from any cause.

Similarly, the Cardiac Resynchronization in Heart Failure (CARE-HF) trial had similar results, proving significant reductions in all-cause mortality and hospitalization for major cardiovascular events at 29 months in patients with CRT (pacing only) over optimal medical therapy.[15]  It was the first trial to definitively show that CRT (pacing only), even in the absence of ICD therapy, had a mortality benefit.

Three relatively newer landmark studies—REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE),[10] Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT),[9]  and Resynchronization for Ambulatory Heart Failure Trial (RAFT)[8] —investigated the effectiveness of CRT in HF patients with a wide QRS complex and mild HF symptoms (NYHA class I-II). Patients were randomized to CRT plus ICD ("CRT-ON") and CRT alone ("CRT-OFF"). REVERSE showed significant reverse remodeling, MADIT-CRT showed less hospitalization, and RAFT showed significant reduction in mortality in the CRT arm. The CRT benefit shown in these studies is consistent with those from older studies performed in patients with more severe HF symptoms.

A 2018 substudy report of the MADIT-CRT trial indicated that in CRT-treated HF patients, left atrial abnormality on electrocardiography (ECG) appeared to be an ECG indicator of poor long-term outcome in those with LBBB.[20]  The investigators suggested that the P-wave terminal force in lead V1 (PTF-V1) (in which a PTF-V1 of 0.04 mm/s or longer was considered abnormal) provided additional prognostic information in the context of CRT, thereby potentiating the role of ECG in stratifying risk in HF patients.[20]

Preliminary data indicate that not only do elderly patients (≥75 years) undergo CRT with ICD less often than younger patients,[21] but the elderly do not appear to derive a survival benefit with the addition of an ICD.[22]

Updated guidelines on cardiac pacing and cardiac resynchronization therapy (CRT) were published in August 2021 by the European Society of Cardiology (ESC) and European Heart Rhythm Association (EHRA) in Europace.[23, 24] Emphasis has been placed on patient-centered care, shared decision making, and appropriate workup/testing prior to pacemaker implantation.

New recommendations include those for pacing after syncope, pacing following transcatheter aortic valve implantation (TAVI), CRT for heart failure (HF) and for prevention of pacing-induced cardiomyopathy, and pacing in various infiltrative and inflammatory diseases of the heart, as well as in different cardiomyopathies.[23, 24] New sections include those on pacing the His bundle (HBP) and the left bundle branch (LBB), as well as on evaluation of suspected or documented bradycardia or conduction system disease.

Select Key Messages

Cardiac pacing

Cardiac pacing is indicated in patients with:

• Sinus node dysfunction (SND), including those with bradycardia–tachycardia type of SND, when symptoms are clearly attributed to bradyarrhythmia

• Sinus rhythm (SR) and permanent or paroxysmal third- or second-degree type 2 or high-degree atrioventricular block (AVB), irrespective of symptoms

Single-lead ventricular pacing is indicated in the setting of permanent atrial fibrillation (AF) and permanent or paroxysmal AVB.

In the setting of syncope and unexplained falls, determine the diagnosis using available diagnostic methods before considering pacemaker therapy.

Cardiac resynchronization therapy

CRT is recommended in patients with symptomatic HF and left ventricular (LV) ejection fraction (EF) ≤35% despite optimal medical therapy (OMT) who are in SR and have LBB block (LBBB) QRS morphology, when QRS duration is ≥150 ms. Consider CRT in these patients when QRS duration is 130–149 ms.

In the setting of non-LBBB QRS morphology, less convincing evidence exists for the benefit of CRT, especially with normal PR and QRS duration < 150 ms. CRT should not be used in patients with HF and QRS duration < 130 ms unless ventricular pacing is needed.

Consider CRT in those with permanent AF, symptomatic HF, LVEF ≤35%, and QRS ≥130 ms who remain in New York Heart Association (NYHA) class III or ambulatory IV despite OMT.

Consider AV junction (AVJ) ablation for those with AF and CRT when at least 90-95% effective biventricular pacing is not achievable.

For patients with high-degree AVB and an indication for cardiac pacing who have HF with reduced EF (HFrEF) (LVEF < 40%), the ESC/EHRA recommend CRT rather than right ventricular (RV) pacing.

His bundle pacing

HBP may:

• Result in normal or near-normal ventricular activation; it is an attractive alternative to RV pacing

• Be considered for select patients with AVB and LVEF >40%, who are anticipated to have >20% ventricular pacing

• Correct ventricular conduction in a subset of patients with LBBB; thus, it may be used in lieu of biventricular pacing for HBP-based CRT in select patients

In patients offered HBP, individual consideration should be given for implanting an RV lead used as “backup” for pacing. In patients treated with HBP, tailor the device programming to the specific requirements of HBP.

Consider implantation of a leadless pacemaker when no upper extremity venous access exists, when the risk of device pocket infection is particularly heightened, and in patients on hemodialysis.

TAVI, other surgeries, and perioperative considerations

Undergoing TAVI raises the risk of developing AVB. Base decisions regarding post-TAVI cardiac pacing on preexisting and new conduction disturbances. Consider ambulatory electrocardiographic (ECG) monitoring for 7-30 days or electrophysiologic studies (EPS) in post-TAVI patients who have new LBBB or progression of a preexisting conduction anomaly, but who do not yet have any indication for a pacemaker.

In patients undergoing surgery for endocarditis or tricuspid valve surgery who have or develop AVB under surgery, consider placing epicardial pacing leads during surgery.

To reduce the risk of complications:

• Administer preoperative antibiotics before cardiovascular implantable electronic device (CIED) procedures

• Chlorhexidine–alcohol should be preferred for skin antisepsis

• Attempt cephalic or axillary vein access as first choice

• Avoid heparin bridging in CIED procedures to minimize the risk of hematoma and pocket infection

• Consider use of an antibiotic-eluting envelope in CIED reintervention procedures to lower the infection risk

Radiation therapy can be offered to patients with a pacemaker or CRT—provided individualized treatment planning and risk stratification is done beforehand and the device is interrogated as recommended around the period of radiation therapy.

For more information, please go to Transvenous Cardiac Pacing and Transcutaneous Cardiac Pacing.

Go to 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: Developed by the Task Force on cardiac pacing and cardiac resynchronization therapy of the European Society of Cardiology (ESC) With the special contribution of the European Heart Rhythm Association (EHRA) for full details.

Preprocedure

Before implantation of cardiac resynchronization therapy (CRT), educate patients about the indication(s), utility, and potential complications that may be encountered during the procedure. 

Following an explanation of the procedure, patients should be offered the opportunity to ask any questions they might have about the procedure.

Query patients whether they are sensitive to or are allergic to any medications, iodine, latex, tape, or anesthetic agents (local and general). Also, elicit all medications (prescription and over-the-counter) and herbal or other supplements patients may be taking.

Educate patients to notify physicians if they have heart valve disease, as prophylactic antibiotics may be required prior to the procedure. Also determine whether patients have a history of bleeding disorders or if they are taking any anticoagulants, aspirin, or other medications that affect blood clotting. It may be to stop some of these medications prior to the procedure.

Patient will need to fast for a certain period of time prior to the procedure, usually overnight.

Patient may receive a sedative prior to the procedure to help them relax.

After obtaining a signed informed consent, surgeons may proceed with the procedure.

Details regarding the pre- and postprocedure care are summarized in the following sections.

Postprocedure

Educate patients about the following points:

• After the procedure, patients may be taken to the recovery room for observation or returned to the hospital room. A nurse will monitor their vital signs.
• Patients should inform the nurse immediately if they feel any chest pain or tightness, or any other pain at the incision site.
• After the period of bed rest has been completed, patients may get out of bed with assistance. A nurse will check their blood pressure while patients lie in bed, sit, and stand. Advise patients to move slowly from the bed to avoid any dizziness from the period of bedrest.
• Patient will be able to eat or drink once completely awake.
• The insertion site may be sore or painful, and pain medication may be administered, if needed.
• Once the patients' blood pressure, pulse, and breathing are stable and they are alert, they will be taken from the recovery room to their hospital room or discharged to home.
• If the procedure is performed on an outpatient basis, patients may be allowed to leave after having completed the recovery process. However, it is common for patients to spend at least one night in the hospital for observation after implantation of an implantable cardioverter-defibrillator.

The European Society of Cardiology (ESC) developed guidelines in collaboration with the European Heart Rhythm Association (EHRA) and provided recommendations for preimplantation of cardiac resynchronization therapy (CRT), as outlined below.[25]

Recommended

The following are preimplantation recommendations[25] :

• Careful evaluation of comorbidities and an estimate of life expectancy
• Thorough preimplant history and physical examination, including review of vital signs and laboratory tests
• Stable heart failure (HF) status in CRT candidates on guideline-directed medical therapy (GDMT) prior to implantation
• Preimplant comprehensive echocardiogram for quantification of left ventricular (LV) ejection fraction (LVEF) and assessment of cardiac size and function
• Preimplant 12-lead electrocardiogram (ECG), including measurement of QRS duration (QRSd) (120–130 ms) and characterization of QRS morphology
• Continued therapy at a reduced dosage in preoperative patients at high thromboembolic risk on oral anticoagulant therapy with warfarin, with close monitoring of the international normalized ratio (INR 2–3); postoperative use of heparin is discouraged
• Preoperative infection prophylaxis with an antibiotic that has in vitro activity against staphylococci

May be useful

The following preimplantation recommendations may be useful[25] :

• Preimplant formal functional status testing including a quality of life (QOL) measure to monitor CRT response
• Cardiac magnetic resonance imaging (cMRI) to assess cardiac function and provide detailed information about viable myocardium in the distribution of a coronary sinus (CS) branch vein considered for left ventricular (LV) lead implant
• Venous anatomic mapping with computed tomography angiography (CTA) in certain patient populations (eg, those with prior LV lead implant failure or those at risk for abnormal venous anatomy)
• Development of a preimplant strategy to identify and manage atrial fibrillation or frequent premature ventricular contractions (PVCs) that may impair the ability of CRT to deliver therapy continuously
• Patients at low to moderate thromboembolic risk on oral anticoagulant therapy with warfarin: Continued therapy at a reduced dosage (INR 1.5-2) or withholding therapy 3-5 days preoperatively to minimize bleeding risk
• Patients at low-moderate thromboembolic risk on direct thrombin or factor Xa inhibitor agents: Withholding such therapy 2-3 days before surgery to minimize bleeding risk.

Not recommended

CRT implantation should be deferred in patients with acutely decompensated HF, who are dependent on inotropes, or who have unstable ventricular arrhythmias until their medical status is improved.[25]

Echocardiographic dyssynchrony assessment should not be used to exclude patients from consideration for CRT.[25]

The European Society of Cardiology (ESC) and the European Heart Rhythm Association (EHRA) have provided cardiac-resynchronization therapy (CRT) follow-up recommendations, as outlined below.[25]

Recommended

A close degree of cooperation is recommended in the follow-up of the CRT recipient between the heart failure (HF) and electrophysiology follow-up physician.

A minimum in-clinic follow-up interval of 6 months is strongly recommended for CRT recipients.

Remote monitoring and follow-up in addition to in-clinic follow-up is recommended. Patients should be encouraged to initiate a remote transmission if new symptoms or concerns arise.

Follow-up visits that include a patient history, physical examination, device interrogation and testing, and systematic analysis of device data is recommended.

Optimization including upward titration of heart failure drug therapies, if appropriate, is recommended to maximize response to CRT.

Evaluation of LV function or other adjuncts to assess heart failure progression or regression is recommended during follow-up.

May be useful

Catheter ablation of the atrioventricular (AV) node in the setting of atrial fibrillation with native conduction can be useful if CRT is not being delivered consistently.

For the overwhelming majority of patients undergoing cardiac resynchronization therapy (CRT), conscious sedation combined with local anesthesia provides satisfactory analgesia. In rare cases, general anesthesia is required (eg, for children or for patients who are difficult to sedate).

Access to the coronary sinus (CS) for implantation of the left ventricular (LV) lead may be achieved via the axillary, subclavian, or cephalic vein. It is preferable to use an access site separate from the one used for the other leads; this allows easier sheath manipulation. Unfortunately, a separate access site may not be an option in certain patients (eg, those with existing hardware who require an upgrade to a CRT device).

The site where the device will be implanted (ie, the right or left side of the chest wall) is determined mainly by the patient’s preference or by the location of a preexisting device. In additional to chest wall placement, CS and LV lead placement from the femoral vein has been described, with or without pull-through to the subclavian vein[26, 27] ; however, such approaches are reserved for extraordinary circumstances. Further information on device implantation is available elsewhere (see Permanent Pacemaker Insertion).

If diaphragmatic or intercostal muscle capture occurs, several techniques can be used to overcome it. Changing the pacing vector (electronic repositioning) of the lead, the position of the lead, or the voltage output may be successful.

To facilitate stable left ventricular (LV) lead placement, it is practical first to place the right ventricular (RV) pacing lead and then to advance the LV lead into the coronary sinus (CS) branch, leaving the sheath in place. After the right atrial (RA) lead is positioned, the LV lead guiding sheath is removed, and the LV lead is sutured in place.

RV lead

In most cases, the delivery system sheath is passed over a guidewire into the RA and then advanced slowly into the RV, where 90-180° of counterclockwise rotation is subsequently applied while the sheath is gently withdrawn and then advanced. This maneuver generally brings the sheath to the CS or the vicinity of the CS os, allowing easy cannulation of the CS with a guidewire.

If cannulation of the CS proves difficult, it may be necessary to use a combination of the outer and inner sheaths to engage the CS. A number of different inner catheters, with different angulations of the terminal portion, are available. Injection of a small volume of contrast material may be used to facilitate identification and cannulation of the CS os.

A common difficulty is the inability to reach the CS os. If this problem is encountered, sheaths with a longer reach or an inner catheter may be used to extend the sheath and thereby enable cannulation.

LV lead

Although it may be possible to place the LV lead without knowing the anatomy of the CS and its branches, it is prudent to obtain a CS phlebogram to direct the selection and placement of this lead. Injection of a small volume of contrast material provides relevant information, and it is unlikely to cause significant deterioration of renal function, even in patients with renal dysfunction.

In most patients, a balloon angiography catheter should be used for contrast injection to achieve optimal opacification of the CS and its branches. To accomplish this, the outer sheath should be advanced relatively deeply into the CS, through which the angiography catheter is advanced. As the catheter approaches the end of the sheath, the sheath is slowly retracted to expose the balloon tip; this step minimizes the risk of CS dissection, which may occur if the angiographic catheter is advanced instead.

The entire system may be carefully retracted to adjust its placement and to make sure that all branches are visualized with contrast injection. Usually, injection of 10-15 mL of undiluted contrast material is necessary to achieve good opacification. The balloon should remain inflated during initial contrast injection and then deflated at the last phase of the phlebogram to allow visualization of any venous branches proximal to the balloon.

Phlebography should be obtained in the following two projections:

• 35° left anterior oblique (LAO): This projection allows visualization of branches and their location along the LV wall (ie, posterior, lateral, or anterior)

• Anteroposterior (AP) caudal: This projection allows visualization of the bifurcation of the branches from the main body of the CS

Successful resynchronization can be achieved with placement of the LV lead in almost any CS branch, provided that the site is in the proximal third to the middle third of the LV.[1] In small trials, placement of the lead in areas with maximal dyssynchrony has been associated with better CRT outcomes. Unfortunately, it is not always possible to place the leads in these areas, whether because of the lack of appropriate branches overlying the area of dyssynchrony, because of poor capture, or because of diaphragmatic capture.

Other markers associated with success of resynchronization include the physical distance between the RV and LV leads in the LAO projection (the larger the better) and late sensing on the LV lead (the terminal portion of the QRS). The final decision for branch selection should be based on consideration of the following factors:

• Ease of cannulation

• Expected stability of the lead (ie, likelihood of dislocation)

• Possibility of diaphragmatic capture

Several techniques have been described for branch cannulation; the choice of technique should be dictated predominantly by the patient’s anatomy. For example, branches with acute-angle origins can often be cannulated with an angioplasty wire without any difficulty.

Frequently, however, branches originating at right or obtuse angles are difficult to cannulate. There are two techniques that can be used in such situations. An inner catheter may be inserted near the preselected branch so that the guidewire can be advanced into the branch. Once this is accomplished, the catheter may be exchanged for a packing lead while the wire position is maintained.

Alternatively, a larger-lumen inner catheter may be used to allow delivery of the pacing lead. This technique has been simplified by using a lead with an exaggerated curve, through which a stylet or angioplasty guidewire is advanced to direct the lead tip into the appropriate venous branch.

In some patients in whom cannulation of the branches is achieved with the inner catheter and branch size is satisfactory, the CS sheath may be gently advanced over the inner catheter to allow selective branch cannulation. At that time, the inner catheter may be removed without the need for an exchange wire, and the pacing lead may be advanced through the main sheath whose tip is located in the preselected branch.

Difficulties in lead placement

Inability to cannulate the preselected venous branch is usually due to tortuosity of the branch. The best way of overcoming this difficulty is to use multiple angulations to explore the anatomy and to make sure the lead is advanced coaxially to the wire and the branch. Different lead sizes and shapes can also be used. 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 more often as the leads are more frequently placed in the proximal third to the medial third of the LV vein. To prevent this, a lead with a more aggressive curve or active fixation may be used. Stenting may also be used to improve lead stability. With this technique, two guidewires are placed in the venous branch, with one used for advancement of the pacing lead and the other used for placement of a stent, which is deployed at low pressure to secure the pacing lead.

Unusual lead placement techniques

Some patients may have extensive connections between distal aspects of the CS branches, and these connections can be explored for lead placement. Such exploration may be particularly helpful when the number of branches is limited or when the most desirable branches are difficult to cannulate. In these circumstances, it is often possible to access the middle cardiac vein and advance the lead to the lateral LV via distal branch connections.

When cannulation of the CS is very difficult, different sheath shapes may be tried. Alternatively, different electrophysiologic catheters (either fixed curve or adjustable) may be used for CS access, or advancement of the guide sheath may be attempted. In rare cases, advancement of the guide sheath may be blocked by stenosis or a muscle band at the proximal portion of the CS. If a muscle band is present, one has to wait for diastole to advance the sheath.

Splitting of LV sheath

Splitting of the LV sheath is a critical part of the procedure. If it is not done properly, it may result in dislodgement of the lead. Before the sheath is split, the guidewire should be advanced past the end of the lead to provide maximal support. Subsequently, the pacing lead must be securely placed within the splitter.

Splitting should be done expeditiously and efficiently. When the sheath is split in a very slow fashion, it can point inferiorly upon exiting the CS os and consequently can place undue tension on the lead that may lead to dislodgement. When the sheath is split rapidly, the transit over the CS os is very quick, and undue traction on the lead is avoided. Exercise caution in splitting the short sheath that is used for vascular access.

Once splitting is completed, the angioplasty wire should be withdrawn to allow deployment of the lead with its curve. At this time, the slack in the lead should be adjusted. Finally, the lead is secured to the pectoralis fascia in the usual manner.

Troubleshooting

Diaphragmatic capture or a change in the capture threshold may be seen soon after implantation as the patient is moved from the procedural table. This occurs because of a change in the anatomic relationship of the heart to the surrounding structures (the diaphragm or the phrenic nerve) or because of a change in lead position. In this situation, electronic repositioning is usually helpful in avoiding diaphragmatic capture and improving the capture threshold.

After lead placement, chest radiography should always be performed (in the posteroanterior [PA] and lateral views) to document lead position. This facilitates assessment for possible lead dislodgement if a change in lead parameters should be observed in the future.

Appropriate device programming should yield reliable biventricular pacing. Only patients with at least 95% of biventricular pacing will benefit from cardiac-resynchronization therapy (CRT); therefore, the atrioventricular (AV) delay should be programmed to be short.

The various device manufacturers have developed several algorithms that allow automatic programming of AV delay as well as right ventricular (RV)-to-left ventricular (LV) delay. However, these algorithms have not been associated with improved outcomes as compared with programming of the AV delay to 130 and 100 msec (paced and sensed, respectively). Another option is to use echocardiography-based parameters for AV optimization, although this is not supported by clinical outcome data.

Typically, the lower pacing rate should be programmed to be about 50 beats/min unless sinoatrial (SA) node dysfunction is present. The maximum tracking rate should be extended as far as is feasible in the device to allow biventricular pacing throughout a wide span of sinus rates. In patients who have SA node dysfunction, rate response should also be programmed.

Complications of Cardiac-resynchronization therapy (CRT) include the following:

• Dissection of the coronary sinus: In most cases, this is of no clinical consequence; if it occurs to a significant extent, the sheath should be removed and the coronary sinus (CS) recannulated, with care taken to ensure that the true lumen is accessed; echocardiography should be performed to assess for the presence of pericardial effusion

• CS perforation or branch rupture: These are very rare events and may be associated with pericardial effusion; usually, they are of little consequence because the venous circulation is a low‑pressure system; however, if pericardial effusion is present, serial echocardiograms may be obtained to evaluate for continuing accumulation or development of tamponade physiology

• Inability to cannulate the CS: In about 5% of patients, either the CS cannot be cannulated or no branches are available for left ventricular (LV) lead placement; in these circumstances, epicardial placement of the LV lead should be seriously considered

• Lead dislodgement: This occurs in approximately 5%-7% of cases but is becoming less common with the development of leads that possess improved fixation mechanisms; if it cannot be overcome by changing pacing vectors, the lead may have to be repositioned