doi: 10.1161/CIRCULATIONAHA.106.655712
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2007;115:2208-2220.)
© 2007 American Heart Association, Inc.
Interventional Cardiac Electrophysiology |
Interventional Electrophysiology and Cardiac Resynchronization Therapy
Delivering Electrical Therapies for Heart Failure
From the Department of Cardiovascular Medicine and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland Clinic Foundation, Cleveland, Ohio.
Correspondence to J. David Burkhardt, MD, Cardiac Pacing and Tachyarrhythmia Devices, Department of Cardiovascular Medicine, Cleveland Clinic Foundation, 9500 Euclid Ave, Desk F15, Cleveland, OH 44195. E-mail burkhaj1{at}ccf.org
 |
Abstract |
|---|
Top
Abstract
IntroductionImplantable devices have become a readily available option for patients with heart failure. Not only do these patients develop bradycardia and ventricular tachycardia, but their ventricular dysfunction can often improve with cardiac resynchronization therapy. However, this is a complex and rapidly developing clinical science for which the physician chooses techniques and selects patients on the basis of the results of clinical trials, clinical experience, and rapidly evolving tools. The results depend on the interplay of these complex variables. Placement of the left ventricular lead has forced the device physician to develop new skills and/or interdisciplinary relationships with physicians with vascular intervention, imaging, and surgical skills. Familiarity with the cardiac venous anatomy, occlusive venography, venoplasty, guide wire tools, guiding catheters, stenting, and new intracardiac visualization and magnetic intracardiac lead positioning tools are examples of just a few of the novel skills that are useful in the delivery of cardiac resynchronization therapy. Beyond implantation, these patients and devices require specialized follow-up with continued medical therapy and echo-guided adjustments of device programming. Finally, there are ongoing controversies and many as yet unanswered questions that are the subject of ongoing and planned clinical trials.
Key Words: electrical stimulation • heart failure • pacemakers • defibrillators, implantable
|
Introduction |
|---|
Patients with advanced congestive heart failure (CHF) on maximal medical therapy have had very limited options until recently. The advent of cardiac resynchronization therapy (CRT) has revolutionized the treatment of these patients. Many patients with advanced CHF demonstrate dyssynchrony by evidence of a widened QRS complex on the EKG. Most frequently this takes the form of a left bundle-branch block morphology, but right bundle-branch block morphology and intraventricular conduction delay are also less frequently present.1,2 Electrical dyssynchrony usually implies that different portions of the ventricle contract at different times, unlike that of a normal heart in which contraction of all segments is nearly simultaneous. The presence of a widened QRS itself in the presence of CHF symptoms is associated with increased mortality.3,4 Dyssynchrony on EKG, particularly of the left bundle-branch type, is associated with delayed activation of the left lateral wall, mitral regurgitation, impaired left ventricular filling, and reduced measures of cardiac contractility.5–8 CRT operates on the premise that attempts to normalize the timing of activation of the left and right ventricle or lateral wall and septum may improve the consequences of this impaired activation.9
Multiple trials have shown that CRT improves heart failure symptoms in the majority of recipients.10–14 These trials include the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial, which studied 453 patients. All patients had a CRT device implanted and were randomized to therapy on or off. As compared with the control group, patients assigned to CRT experienced improvements in 6-minute hall walk distance, quality of life scores, and New York Heart Association (NYHA) functional class. The Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial studied 1520 patients. Patients were randomly assigned to optimal medical therapy, optimal medical therapy + CRT with a pacemaker, or optimal medical therapy + CRT with a pacemaker-defibrillator. The primary end point was a composite of death or hospitalization from any cause. CRT with a pacemaker reduced the risk of the primary end point by 34%, and CRT with a pacemaker-defibrillator reduced the risk of the primary end point by 40%. The Cardiac Resynchronization in Heart Failure (CARE-HF) trial included 813 patients randomly assigned to medical therapy alone or with CRT. The primary end point was time to death from any cause or an unplanned hospitalization for a major cardiovascular event. This trial did not combine defibrillator therapy with CRT. The primary end point was significantly reduced in the group that received CRT. The secondary end point of death from any cause was also significantly reduced in the group that received CRT.15
|
Patient Selection and Therapeutic Results |
|---|
Based on the results of many trials, candidates for CRT include those with dilated cardiomyopathy (either ischemic or nonischemic) with an ejection fraction of
35%, a QRS duration of 
120 milliseconds on EKG, NYHA class 3 to 4 CHF symptoms despite optimal medical therapy such as ß blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and loop diuretics.16 Most patients that meet criteria for CRT are also candidates for defibrillator therapy.17 Before implantation, patients need to be evaluated according to history and physical data that concentrate on classification of heart failure class, medical optimization, and potential reversible causes. Preoperative testing should include EKG for QRS duration and classification of dyssynchronous pattern as well as echocardiography for evaluation of ejection fraction, mitral regurgitation, and left ventricular dimensions. Special attention should be given to the EKG. Computer-derived values of QRS duration frequently underestimate the true duration of the QRS complex. Terminal forces may not be included in the estimate, and hand-calipered durations may reveal a QRS of longer duration. The echocardiogram may also be used to evaluate dyssynchrony if the indication for CRT is borderline or to assist in decision making.18 Echo-based ventricular dyssynchrony may be classified as interventricular or intraventricular. Interventricular dyssynchrony refers to delayed ejection of one of the ventricles, and intraventricular dyssynchrony describes delay in contraction of segments within the left ventricle.19 Patients with QRS durations <130 milliseconds may have significant echo-defined dyssynchrony and have been found to benefit from CRT.20 If the patient has newly diagnosed CHF or the heart failure and left ventricular dysfunction is felt to be reversible, such as a case with rate-related cardiomyopathies, then medical therapy should be instituted and a reevaluation performed after at least 3 months before CRT therapy is initiated. In patients who meet indications for device-based therapy, such as a pacemaker or defibrillator, but who would not usually qualify for CRT therapy because of recent surgery, revascularization, or myocardial infarction, then the operator may choose to proceed with CRT therapy to avoid the additional risk of a system change in the near future. Patients with reduced left ventricular function who require pacing for complete heart block have been shown to have improved left ventricular ejection fraction and quality of life with biventricular pacing compared with right ventricular pacing in the Homburg Biventricular Pacing Evaluation (HOBIPACE) trial.21 Patients with reduced left ventricular function and atrial fibrillation who underwent atrioventricular (AV) junction ablation also appeared to benefit from biventricular pacing compared with right ventricular pacing in the Post AV Node Ablation Evaluation (PAVE) study.22 Patients who will have pacing-induced dyssynchrony should also receive CRT. Patients who are not candidates for CRT include those who are not ill enough or those who might be too ill. In patients with reduced left ventricular function but no CHF symptoms at all, the risk of the procedure likely outweighs the potential benefits. Patients who are nonambulatory or require continuous intravenous inotropes are likely too ill to receive enough benefit to justify the risk. Patients with a diagnosis that would result in death within 6 months are generally not considered to be candidates.
In CHF patients who meet standard criteria, CRT has been shown to improve objective and subjective signs of CHF. Improvements have been noted in heart failure questionnaires, NYHA class, ejection fraction, mitral regurgitation, quality of life scores, left ventricular pressure, cardiac index, and pulmonary capillary wedge pressure.23–25 Patients have also been found to undergo ventricular remodeling by diminishing left ventricular dimensions.26,27 These improvements appear to last over time, although mortality remains higher than in the population without CHF.28–30 Table 1 lists the reported statistically significant improvements in parameters recorded in major CRT trials. In a large trial, CRT alone has been associated with decreased mortality, but CRT and defibrillation therapy have been repeatedly shown to reduce mortality.13,15
|
The effect of CRT on arrhythmic burden appears to be modest at best. There appears to be no significant reduction in atrial fibrillation burden in those with CRT.31 Cases have been reported of CRT inducing ventricular arrhythmias, but several trials report a reduction in these events.32–36 A review of the 2 largest CRT trials did not show significant increases or decreases in ventricular arrhythmia.37
|
Pacing for Resynchronization |
|---|
In CRT, pacing leads are placed in the right ventricle, right atrium, and a branch of the coronary sinus, although originally the left ventricular leads were placed on the epicardium in the operating room.38 The coronary sinus typically has several branches: middle cardiac vein, posterior vein, posterolateral vein, lateral vein, anterolateral vein, and anterior vein (Figure 1).39 The preferred site of the coronary sinus lead is in the posterolateral and lateral location. This can be achieved from the venous branches of the same name, but the venous system is variable, and the distal segments of many of the branches may lead to the posterolateral position. Evidence suggests that these locations are associated with the greatest response rates.40 In the original trials, the pacemaker was programmed to the DDD mode at a rate of 40 beats per minute at an AV delay shorter than the patient’s intrinsic conduction. Most patients did not have sinus node dysfunction.10,13,15 This resulted in tracking of sinus rhythm with biventricular pacing. Patients with atrial fibrillation were excluded from these trials. In earlier trials, the right ventricular lead and coronary sinus lead were electrically connected together to conform to the ventricular pacing port of a dual-chamber system. As a result, simultaneous activation of both ventricles was also required. The coronary sinus lead was a unipolar lead, and pacing outputs were determined by the highest threshold of either lead. Advances have resulted in devices with separate left ventricular and right ventricular outputs, bipolar leads of various shapes and sizes, and the ability to alter the timing between both ventricular leads. CRT has also been combined with defibrillation therapy on the basis of the results of trials that showed reduced mortality with defibrillator therapy in patients with reduced left ventricular function, such as the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).14,17,41
|
|
CRT Lead Delivery |
|---|
The major limitation to delivery of CRT therapy is anatomic. Because the left ventricular lead is delivered via the coronary sinus, and the preferred position of the lead is lateral, a prospective patient must have an accessible coronary sinus and a branch located in the posterior and lateral position large enough to accept a pacing lead. It can be difficult to access the coronary sinus in some patients. The ostium of the coronary sinus is located inferior and posterior to the tricuspid valve. It is protected inferiorly by the thebesian valve and laterally by the crista terminalis (Figure 2). The coronary sinus ostium may be tortuous, angulated, or vertically positioned. Patients with markedly enlarged right atria or significant tricuspid regurgitation may be very difficult to cannulate. Significant variations exist in the coronary sinus and tributary anatomy, much more so than the usual right atrial and ventricular anatomy. Vessels vary widely in size, tortuosity, course, and distribution. Patients may have very large vessels that do not allow a lead to stay in place, small vessels that do not allow passage of a lead, or tortuous or angulated segments that make delivery difficult or impossible. Also, previous mitral valve surgery may alter the anatomy of the venous system. In general, other types of cardiac surgery such as coronary artery bypass or aortic valve surgery do not markedly alter the anatomy of the coronary sinus or its branches. With the assumption that the lead is placed in an appropriate position and maintains a stable position, the capture thresholds need to be appropriate to ensure ventricular capture and avoid premature battery depletion. Previous posterior and lateral myocardial infarction may limit the ability to capture myocardium in this area. Another limitation is the presence of the phrenic nerve near the area of optimal lead position. The left phrenic nerve, which is responsible for diaphragmatic stimulation, runs along the posterior and lateral border of the heart. Pacing near this nerve may result in diaphragmatic stimulation at the programmed pacing rate, which is very uncomfortable for the patient and not tolerated for long periods of time. Bipolar leads and leads with programmable pacing configurations may diminish this possible complication.42,43
|
Cannulation of the coronary sinus has become easier with improved technology. Sheaths have been developed to take advantage of the existing anatomy. Outer sheaths with a large primary curve and a smaller secondary curve allow support from the lateral atrial wall and superior vena cava (Figure 3). The preferred technique of coronary sinus intubation is to advance the sheath into the right ventricle and withdraw it with counterclockwise rotation. This maneuver avoids the lateral crista terminalis and inferior thebesian valve because the approach is medial and superior. Cannulation of the coronary sinus tends to be easier with a left-sided implant. The angulation of the subclavian venous system relative to the superior vena cava from the left side allows support from the superior vena cava and right atrium. In a right-sided implant, the angulation tends to force the sheath medially and the supportive effect is lost. A standard 0.035-mm diameter wire, inner catheter, electrophysiologic recording catheter, and contrast dye may be used to assist in this process. Contrast dye improves the visualization of the anatomy in difficult cases. It may reveal unusually high ostia, an overriding thebesian valve, an early bifurcation, or separate ostium of the middle cardiac vein. Most frequently, it reveals that the sheath is in the sulcus of right atrium and tricuspid valve, which suggests that a sheath with a longer reach is required. The deflectable electrophysiologic recording catheter adds reach and maneuverability to the system. The signals obtained from the distal poles of the catheter also assist in the definition of the ostium location. The coronary sinus has a very typical electrical appearance with a large atrial electrogram and a smaller ventricular electrogram. Fluoroscopy alone may be helpful. The "fat stripe" serves as a marker for the location of the coronary sinus. Like peripheral veins, the coronary sinus may contain valves. A valve is typically present in the mid-coronary sinus. This may prevent advancement of the catheter or wire. Careful manipulation of the instruments can usually overcome this obstacle.43,44
|
Once the coronary sinus has been cannulated, balloon occlusive venography is performed to identify the existing anatomy and possible target vessels. The venogram should be performed in at least 2 oblique projections to fully understand the anatomy. The vessels are analyzed for location, size, and angulation and tortuosity of the initial segments. The target vessel is identified, and a plan for placement of the lead, which includes the decision of what vessel to use, is formulated based on the anatomy. As stated, the posterior and lateral position results in the best response rates. One study reports that if the left ventricular electrogram is located in the latter half of the QRS complex, then response rates are higher.45 Our current technique involves the attempted placement of the lead in the most posterior and lateral position as possible on the basis of several fluoroscopic projections. If multiple vessels are available for this location, then we may attempt to find the latest occurring electrogram. Conventional electroanatomic mapping software has been used to locate the latest occurring signals and reconstruct the anatomy.
Several technologies are being evaluated to help refine optimal lead positioning. Echocardiographic and computed tomographic evaluation of delayed mechanical activation are also being tested to identify individual lead placement that maximizes resynchronization.46 The benefit of computed tomography is that coronary sinus anatomic information is obtained in addition to the mechanical activation.47 Use of transthoracic echocardiography in the electrophysiology laboratory can be tedious and difficult. Image quality may be suboptimal as a result of the flat position of the patient, ambient lighting, and limitation of the sterile field. Intracardiac echocardiography shows promise as an adjunctive tool. Vector velocity imaging has been tested in conjunction with intracardiac echo to refine lead position. The lead can be placed into several positions and a visual or graphic evaluation can be performed with pacing at that location. The best parameters may result in a better lead position.48
If the vessel chosen is at least of moderate size and does not appear to have a difficult anatomy, the operator may elect to proceed with the lead and an inner 0.015-mm diameter guide wire. The wire is advanced into the vessel, and the lead is advanced over this wire. If the initial segment of the target vessel appears challenging, then an appropriately shaped inner sheath may be used to deliver the wire or the wire and lead. Very difficult branches may require inner catheters that are capable of lead delivery. These catheters are shaped so that they are supported from the opposite wall of the coronary sinus body, which allows appropriate forward pressure to be applied to the lead. These catheters are available in various shapes that conform to differing anatomies. These sheaths may also straighten out tortuous segments for delivery. Occasionally, techniques such as venoplasty are required for significant stenosis of the target branch. After the lead is advanced, the site is tested for capture thresholds and presence or absence of phrenic nerve stimulation. The choice of lead depends on the anatomy of the branch. In general, if the branch is large, a larger diameter lead is chosen. If the branch is very large and possible dislodgement is a concern, a lead with a curled or sigmoid shape may be chosen. Bipolar leads are used most frequently because of the ability to program different configurations to overcome phrenic nerve stimulation or elevated pacing thresholds. Unipolar leads are used for sizing purposes. Leads with the smallest and largest diameters are unipolar and may be used for vessels that require these sizes. If the site is acceptable, then the sheath is removed, usually by mechanical splitting. Sheaths may have an inner wire braiding. This type of construction requires that a razor-bladed splitting device be used to cut the braids. This process may dislodge the lead. Splitting of the sheath should be performed under fluoroscopic guidance to ensure that the lead is not rotated or retracted during the process.43
When a coronary sinus lead is added to an existing system, additional challenges may be present. The presence of preexisting leads increases the possibility of occlusion of the subclavian system. If this occurs, the access for the coronary sinus lead can be performed proximal to the site of occlusion; however, this medial approach may increase the risk of lead failure and pneumothorax. Extraction of one of the exiting leads may be performed to allow for access for new leads. Alternatively, the system may be implanted from the opposite side, but this presents a new set of possible complications. The existing leads may be used in the generator if testing reveals appropriate function.
The complication rates associated with implantation of CRT have been remarkably low. The most common complication is inability to deliver coronary sinus pacing for one of the reasons mentioned above, but the overall delivery rate exceeds 90%.49 The need for reoperation to replace or reposition the coronary sinus lead occurs in 6% of cases. Dissection or perforation of the coronary sinus occurs in up to 4% of patients, but tamponade results in <1% of implants.50 Other infrequent complications include pneumothorax, complete heart block, infection, and hematoma. The rate of death associated with implantation is <0.5%.49 Table 2 reports the range of complications from 3 major CRT trials.
|
Most coronary venous dissections do not result in tamponade and do not require abandonment of the procedure. If a dissection occurs, then the outer sheath should be withdrawn and a wire used to find the true lumen of the coronary sinus. Once this is located, then the sheath may be advanced over the wire. If the tear impedes the advancement of the system, a large-diameter angioplasty balloon can be inflated and withdrawn to seal the tear. In the rare event that tamponade occurs, this usually responds to pericardiocentesis. If the patient does not respond or the blood continues to accumulate in the pericardial sac, then a surgeon should be called for evaluation.
|
Technological Advances |
|---|
New technologies exist and are being tested to improve the placement of the coronary sinus lead. Endoscopic catheters that allow direct visualization are being evaluated (online-only Data Supplement). These provide remarkable pictures of the anatomy in real time and in motion. The ability to directly visualize the obstacles may improve the ability to overcome them as well as limit the time spent struggling with implantation based on fluoroscopy and general knowledge of location of the coronary sinus.51 Another catheter that allows visualization by an attempt to filter out red blood cells has been used clinically and can reveal side branches without the need of contrast (Figure 4). This catheter can deliver some remarkable images, but it is unreliable. It also has a limited depth of field. Further refinement of these concepts may change the method of coronary sinus canalization. This technology could also be used to refine the positioning of the other leads, such as placement of the atrial lead near Bachman’s bundle.
|
Remote magnetic navigation uses maneuverable rare earth magnets to allow the control of a magnetic field. A magnet-tipped wire can be manipulated in this field to bend in any prespecified direction. The wire can be directed on the basis of the operator’s desire or of anatomy from venography. With the use of 2 orthogonal projections, the vectors that correspond to a specific site in the venous anatomy can be calculated, which results in a virtual roadmap of vectors (Figure 5). Other data such as preprocedural computed tomography can be imported and used as a guide to determine the vectors. This technology is useful in traversing a wire across very tortuous segments.52 The main limitation, that although a wire can be inserted into a branch, the lead may not follow, remains. This procedure is also limited to the technology of the current sheaths, leads, and wires. Magnet-tipped sheaths and delivery systems are being developed for future use.
|
|
Epicardial Lead Placement |
|---|
Most of the aforementioned technologies are being developed to overcome the limitations inherent in relying on coronary venous anatomy. The minimally invasive subxiphoid epicardial approach is being used by cardiac electrophysiologists for epicardial ablation. This approach uses a spinal needle placed under the xiphoid process and advanced toward the cardiac border. A small puff of contrast is used to confirm position. The pericardial sac is punctured with the needle and a wire is advanced into the space. After the needle is withdrawn, a sheath may be placed over the wire for access into the space.53 This technique lends itself to the placement of an epicardial left ventricular lead, and possibly other leads without the constraint of venous anatomy. Placement of leads in this manner allows a great deal of freedom in lead positioning. This could be combined with methods of rapid lead position evaluation and timing that result in a completely optimized system. Another possible benefit of this approach is the avoidance of the intravascular system, which could reduce the risk of venous occlusion and possibly system extraction. One of the major limitations of this approach is the mechanism of lead fixation. The epicardial space allows for nearly free movement of objects. A lead system would need to be developed that allows for fixation to occur against the myocardium preferentially. Epicardial leads and delivery systems for this approach are being developed. Also, not every pericardial space is easily accessible. Patients with previous open-heart surgery may develop fibrosis in the pericardial space that does not allow access.
Surgical placement of epicardial leads is becoming more commonplace. These leads may be placed at the time of bypass or valve surgery for future use. Minimally invasive and robot-assisted surgeries are also performed to place leads after attempts through the venous system have been unsuccessful. This method does not require the full sternotomy and reduces the patient recovery time.54
|
Follow-Up and Response to Therapy |
|---|
After placement and testing of the CRT device, the patient is discharged to follow-up with an evaluation of response to therapy at a later visit. At the follow-up visit, the patient should be questioned about heart failure symptoms and specific activity limitations compared with before therapy. Electrocardiography should be performed. Appropriate biventricular pacing can be confirmed by EKG. In general, a system with a well-placed coronary sinus lead yields a paced complex in which the initial forces in lead V1 are positive and leads 1 and aVL are more negative (rightward axis shift). This EKG should be compared with the postimplant and baseline EKG.55,56 (Figure 6). Although it would seem that the QRS duration should decrease with CRT, this is not always the case. Also, in a review of many studies, a decrease or increase of the QRS duration does not appear predictive of response.57
|
The device should be completely evaluated for normal functioning parameters. At this follow-up visit, echocardiography is frequently performed to evaluate ejection fraction, left ventricular dimension, mitral regurgitation, and possibly dyssynchrony. At this point, optimization of timing should be performed. If any ventricular remodeling has occurred, then the previously optimized values are likely to have changed.58 The methodology of optimization is discussed later.
At this visit, the key question to be answered is whether the patient has responded to therapy. No standard definition exists for the definition of responders versus nonresponders. Certainly, the main component is the patient’s subjective assessment, but CRT therapy has a profound placebo effect, and distinguishing a true response from this effect can be difficult. Objective measures, such as an exercise evaluation, or echo-based parameters, such as improvement in ejection fraction or left ventricular dimensions, may yield additional useful information. Response to CRT may take several months. In general, most of the benefit appears to occur by 3 months and persists thereafter.30,59,60
Response rates to CRT have been less than ideal. Most trials report response rates in the range of 60 to 70%.60 Several reasons may exist for the lack of response from some patients (Table 3). CRT must first be delivered to be effective. Originally, the coronary sinus lead was adapted to the right ventricular lead to fit into a dual-chamber device, which made threshold testing difficult. Now that separate outputs are available, this testing has become simplified. The presence of atrial fibrillation with rapid response also prevents CRT from being delivered. Lead position appears to be an important factor. The posterior and lateral position, which is opposed to the right ventricular lead, has been shown to be associated with improved response rates. The presence of scar tissue in the posterolateral left ventricle and lack of viable myocardium has been found to be associated with reduced response rates.42,61
|
The evaluation of dyssynchrony by echo parameters has been developed to help define patients who are more likely to respond to therapy. Patients without dyssynchrony are less likely to benefit from CRT.18,62 The field of echo-based dyssynchrony evaluation has been blossoming. Methods to evaluate dyssynchrony range from the very simple, such as measurement of the time from peak excursion of the septal wall compared with the posterior wall on m-mode echocardiography, to complex, multisite, tissue Doppler interrogation and evaluation of rotational dynamics. No consensus exists on the best parameters for dyssynchrony evaluation, but the additional information may be beneficial in borderline cases.63 Table 4 lists some of the methods for evaluation of dyssynchrony and reported definitions.
|
Another method to improve response rates is optimization of CRT timing. All CRT devices allow adjustment of the AV delay. Too long an AV delay permits inefficient diastolic filling, which affects subsequent cycles. Diastolic mitral regurgitation may occur, and direct measures of contractility are reduced. Echo-based evaluation of transmitral Doppler flow is frequently used for optimization. The normal transmitral pattern reveals distinct E and A waves. The E wave represents passive ventricular filling, and the A wave represents atrial contraction (Figure 7). Prolonged AV conduction results in fusion of these 2 waves. The opposite end of the spectrum is an AV delay that is too short. On transmitral Doppler, this is seen by truncation of the A wave. Patients will frequently report increased pulmonary symptoms and pacemaker syndrome type symptoms.64,65 It is a misconception that CRT only treats CHF by treatment of systolic dysfunction. As is seen on the transmitral flow patterns, CRT improves diastolic ventricular filling, which continues to improve over time as the ventricle remodels.66 Another timing variable present in most devices is alterable timing between the left and right ventricular leads. Patients vary in the amount of delay between myocardial segments. Adjustable pacing intervals may improve the resynchronization timing. Echo-based studies reveal that most patients’ optimal timing is not simultaneous.67 Several studies have shown improvement in responder rates, quality of life, exercise time, ejection fraction, direct contractile measurements, and NYHA class compared with simultaneous pacing.67–70 Unfortunately, optimization of ventricular timing can be tedious. It has required use of echo-based parameters such as transaortic velocity time integral, tissue Doppler imaging, or m-mode evaluation. This process can be time-consuming and technically challenging; therefore, it has been mostly reserved for nonresponders. Currently, an intracardiac electrogram-based method is available. It measures the timing between all the leads and calculates the optimal settings based on a mathematical formula. This has been shown to correlate with echo-based optimization and takes only a few minutes to perform.71
|
The treatment of nonresponders should first focus on whether the patient is receiving CRT. The device function should be evaluated to ensure appropriate sensing and capture of all leads. Of course, medical therapy should continue to be optimized after implantation of the device. The patient should also be evaluated for the presence of atrial fibrillation. Atrial fibrillation with a rapid response will prevent the device from pacing if the heart rate in atrial fibrillation is above the programmed rate. This should prompt the need for improved rate control and, possibly, attempts to restore sinus rhythm. A chest x-ray for evaluation of lead position should be performed. If the lead is in a suboptimal position, then repositioning based on the limitations of anatomy could be considered. Surgical epicardial lead placement is another option, because there are no limitations based on venous anatomy. Optimization of atrial to ventricular and right ventricular to left ventricular timing should also be performed in the nonresponder, although technology advancements will allow this to be performed in all patients after implant.
|
Controversies |
|---|
Current controversies in CRT are mostly focused on patients who are indicated or those who are felt to be less likely to respond. Patients with an increased QRS but without dyssynchrony on the basis of echocardiographic criteria have been found to be less likely to respond to CRT. Current indications only use an increased QRS duration as an indication for dyssynchrony. Some feel that some additional evaluation of dyssynchrony may reduce the rate of nonresponders.18,62,72 The QRS-based definition of dyssynchrony may also limit patients who may benefit from CRT. Some patients with decreased QRS durations (ie, <120 milliseconds) have been found to exhibit dyssynchrony. These patients may also benefit from CRT.73 Another controversial issue is the presence of a right bundle-branch block pattern on EKG. The majority of patients with CHF and an increased QRS duration have a left bundle-branch block pattern and activate the left lateral wall later as compared with the right ventricle and septum. It is on the basis of this premise that CRT seems to be beneficial by activating the left lateral wall more synchronously with the septum.5 A right ventricular delay with intact left lateral wall timing would seem to be less likely to benefit from this type of pacing. In fact, some studies have shown that patients with right bundle-branch block are less likely to benefit from CRT; however, the original trials included those with right bundle-branch block patterns, and some maintain that CRT should still be offered to the populations included in these trials.74,75 Another consideration is that either a left bundle-branch block or right bundle-branch block pattern does not truly represent the conduction. These patients have conduction abnormalities in addition to simple bundle-branch blocks.76 Severing the right bundle-branch leads to a QRS duration of about 120 milliseconds in humans. Severing the left bundle-branch results in a QRS duration of about 150 milliseconds. CHF patients may have QRS durations >200 milliseconds. The remainder of the delay is intra- and interventricular, so classification of a patient as right bundle-branch or left bundle-branch block may not truly represent the type of dyssynchronous pattern. Overall, no other criteria for dyssynchrony other than QRS duration have been used in major trials, and no consensus exists on the optimal echo parameters to define dyssynchrony.
One procedure that is frequently performed is the upgrade of an existing pacemaker or defibrillator to a CRT device. This was not addressed in the initial clinical trials; however subsequent smaller studies have shown that these patients seem to benefit from CRT therapy.77,78 These patients may be excellent candidates, because right ventricular apical pacing is a dyssynchronous activation pattern.6 Animal studies have shown that long-term right ventricular pacing induces myofibrillar disarray, asymmetric hypertrophy, and dilatation of the left ventricle.79–81 In humans, echo studies confirm the dyssynchronous activation and reduced efficiency, and others have found elevated serum markers of CHF and stress.82–84 Major trials, such as the Mode Selection Trial (MOST) and the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial, have determined that this type of pacing is detrimental in terms of CHF symptoms, and the current practice is to avoid unnecessary ventricular pacing.85,86 Methods to reduce unnecessary right ventricular pacing include reprogramming the device to maximize the AV delay or changing the mode to VVI at a low rate. Some devices allow programming in the AAI mode with reversion to DDD if AV conduction is lost. Pacing the right ventricle from a site other than the apex, such as direct His bundle pacing, may reduce dyssynchrony and CHF.21 Otherwise, CHF patients with an indication for pacing, who may require a great deal of ventricular pacing, could benefit from a strategy that employs CRT, but this indication is not yet approved. The HOBIPACE study revealed that patients with AV block and left ventricular dysfunction had improved quality of life, left ventricular ejection fraction, and exercise duration with CRT compared with standard dual-chamber pacing.21
Another major controversy is the inclusion of patients with NYHA class 1 or 2 CHF. These patients with minor symptoms may benefit from CRT. Some trials have shown echocardiographic improvement in this population, but, as expected, clinical symptomatic improvement was not seen in such a minimally symptomatic population.87 Some believe that treatment in this population could prevent heart failure symptoms, worsening cardiac function, or adverse remodeling.88
Atrial fibrillation is another area of controversy. Smaller studies have demonstrated improvements in patients with atrial fibrillation, but they were excluded from the major trials.89–91 Patients with permanent atrial fibrillation do not receive the benefit of AV synchrony, but ventricular dyssynchrony may persist. Most trials looking at atrial fibrillation have included patients who underwent AV junction ablation. This ensures appropriate rate control and delivery of CRT therapy; however, AV junction ablation and pacing alone has been shown to improve symptoms and functional capacity in patients with atrial fibrillation and a rapid response.92,93 The PAVE study prospectively evaluated the approach of AV junction ablation and biventricular pacing versus right ventricular pacing in a population with CHF symptoms and showed improvement in functional status, exercise time, and quality of life in the overall population, but most of the benefit was seen in those with preexisting left ventricular dysfunction.22
|
Clinical Research |
|---|
Clinical research seeks to find answers to some of the controversies. The Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT) and the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) trial are evaluating the role of defibrillators with and without CRT in large groups of NYHA class 1 or 2 patients. The Resynchronization Therapy in Normal QRS (RETHINQ) trial is evaluating CRT in patients with CHF and echo-based dyssynchrony with a narrow QRS. Other areas of interest in clinical research include multisite left ventricular pacing. The theory is that resynchronization can be delivered more efficiently if pacing comes from several sites. Another thought is that because most patients have intact right bundle-branch conduction and right ventricular apical pacing has been found to be detrimental, CRT timing could be altered to allow right-sided conduction and pace the left ventricle at a time to allow the electrical forces to meet at the septum.
|
Conclusion |
|---|
CRT has been an important tool in the armamentarium of CHF treatment. Advances in equipment and techniques have improved the delivery of this therapy. Interventional electrophysiologists have been able to overcome some of the limitations inherent in variable coronary venous anatomy with techniques such as venoplasty and inner catheter technology. Timing cycle optimization and guided lead placement may result in response rates >90%. The results of future clinical trials may expand this therapy to those with less severe heart failure or with narrower QRS.
|
Acknowledgments |
|---|
Disclosures
Drs Burkhardt and Wilkoff have received research grants from Medtronic, Boston Scientific, and St. Jude Medical Center, as well as honoraria from Medtronic, Boston Scientific, St. Jude Medical Center, and Stereotaxis. Dr Wilkoff has served as a consultant and/or advisory board member for Medtronic, Boston Scientific, St. Jude Medical Center, and Stereotaxis.
|
Footnotes |
|---|
The online-only Data Supplement, consisting of a movie, is available with this article at http://circ.ahajournals.org/cgi/content/full/ CIRCULATIONAHA.106.655712/DC1.
|
References |
|---|
1. Shamim W, Francis DP, Yousufuddin M, Varney S, Pieopli MF, Anker SD, Coats AJ. Intraventricular conduction delay: a prognostic marker in chronic heart failure. Int J Cardiol. 1999; 70: 171–178.[CrossRef][Medline] [Order article via Infotrieve]
2. Wyndham CR, Smith T, Meeran MK, Mammana R, Levitsky S, Rosen KM. Epicardial activation in patients with left bundle branch block. Circulation. 1980; 61: 696–703.
3. Baldasseroni S, Opasich C, Gorini M, Lucci D, Marchionni N, Marini M, Campana C, Perini G, Deorsola A, Masotti G, Tavazzi L, Maggioni AP. Left bundle-branch block is associated with increased 1-year sudden and total mortality rate in 5517 outpatients with congestive heart failure: a report from the Italian network on congestive heart failure. Am Heart J. 2002; 143: 398–405.[CrossRef][Medline] [Order article via Infotrieve]
4. Iuliano S, Fisher SG, Karasik PE, Fletcher RD, Singh SN. QRS duration and mortality in patients with congestive heart failure. Am Heart J. 2002; 143: 1085–1091.[CrossRef][Medline] [Order article via Infotrieve]
5. Grines CL, Bashore TM, Boudoulas H, Olson S, Shafer P, Wooley CF. Functional abnormalities in isolated left bundle branch block: the effect of interventricular asynchrony. Circulation. 1989; 79: 845–853.
6. Wyman BT, Hunter WC, Prinzen FW, McVeigh ER. Mapping propagation of mechanical activation in the paced heart with MRI tagging. Am J Physiol. 1999; 276: H881–H891.[Medline] [Order article via Infotrieve]
7. Xiao HB, Lee CH, Gibson DG. Effect of left bundle branch block on diastolic function in dilated cardiomyopathy. Br Heart J. 1991; 66: 443–447.
8. Xiao HB, Brecker SJ, Gibson DG. Effects of abnormal activation on the time course of the left ventricular pressure pulse in dilated cardiomyopathy. Br Heart J. 1992; 68: 403–407.
9. Abraham WT, Hayes DL. Cardiac resynchronization therapy for heart failure. Circulation. 2003; 108: 2596–2603.
10. Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, Kocovic DZ, Packer M, Clavell AL, Hayes DL, Ellestad M, Trupp RJ, Underwood J, Pickering F, Truex C, McAtee P, Messenger J. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002; 346: 1845–1853.
11. Auricchio A, Stellbrink C, Sack S, Block M, Vogt J, Bakker P, Huth C, Schondube F, Wolfhard U, Bocker D, Krahnefeld O, Kirkels H. Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. J Am Coll Cardiol. 2002; 39: 2026–2033.
12. Cazeau S, Leclercq C, Lavergne T, Walker S, Varma C, Linde C, Garrigue S, Kappenberger L, Haywood GA, Santini M, Bailleul C, Daubert JC. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med. 2001; 344: 873–880.
13. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004; 350: 2140–2150.
14. Young JB, Abraham WT, Smith AL, Leon AR, Lieberman R, Wilkoff B, Canby RC, Schroeder JS, Liem LB, Hall S, Wheelan K. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial. JAMA. 2003; 289: 2685–2694.
15. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005; 352: 1539–1549.
16. Strickberger SA, Conti J, Daoud EG, Havranek E, Mehra MR, Pina IL, Young J. Patient selection for cardiac resynchronization therapy: from the Council on Clinical Cardiology Subcommittee on Electrocardiography and Arrhythmias and the Quality of Care and Outcomes Research Interdisciplinary Working Group, in collaboration with the Heart Rhythm Society. Circulation. 2005; 111: 2146–2150.
17. Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, Clapp-Channing N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005; 352: 225–237.
18. Pitzalis MV, Iacoviello M, Romito R, Guida P, De Tommasi E, Luzzi G, Anaclerio M, Forleo C, Rizzon P. Ventricular asynchrony predicts a better outcome in patients with chronic heart failure receiving cardiac resynchronization therapy. J Am Coll Cardiol. 2005; 45: 65–69.
19. Burri H, Lerch R. Echocardiography and patient selection for cardiac resynchronization therapy: a critical appraisal. Heart Rhythm. 2006; 3: 474–479.[CrossRef][Medline] [Order article via Infotrieve]
20. Achilli A, Sassara M, Ficili S, Pontillo D, Achilli P, Alessi C, De Spirito S, Guerra R, Patruno N, Serra F. Long-term effectiveness of cardiac resynchronization therapy in patients with refractory heart failure and "narrow" QRS. J Am Coll Cardiol. 2003; 42: 2117–2124.
21. Kindermann M, Hennen B, Jung J, Geisel J, Bohm M, Frohlig G. Biventricular versus conventional right ventricular stimulation for patients with standard pacing indication and left ventricular dysfunction: the Homburg Biventricular Pacing Evaluation (HOBIPACE). J Am Coll Cardiol. 2006; 47: 1927–1937.
22. Doshi RN, Daoud EG, Fellows C, Turk K, Duran A, Hamdan MH, Pires LA. Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the PAVE study). J Cardiovasc Electrophysiol. 2005; 16: 1160–1165.[CrossRef][Medline] [Order article via Infotrieve]
23. Kass DA, Chen CH, Curry C, Talbot M, Berger R, Fetics B, Nevo E. Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation. 1999; 99: 1567–1573.
24. Leclercq C, Cazeau S, Le Breton H, Ritter P, Mabo P, Gras D, Pavin D, Lazarus A, Daubert JC. Acute hemodynamic effects of biventricular DDD pacing in patients with end-stage heart failure. J Am Coll Cardiol. 1998; 32: 1825–1831.
25. Breithardt OA, Sinha AM, Schwammenthal E, Bidaoui N, Markus KU, Franke A, Stellbrink C. Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure. J Am Coll Cardiol. 2003; 41: 765–770.
26. St John Sutton MG, Plappert T, Abraham WT, Smith AL, DeLurgio DB, Leon AR, Loh E, Kocovic DZ, Fisher WG, Ellestad M, Messenger J, Kruger K, Hilpisch KE, Hill MR. Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation. 2003; 107: 1985–1990.
27. Zhang Q, Fung JW, Auricchio A, Chan JY, Kum LC, Wu LW, Yu CM. Differential change in left ventricular mass and regional wall thickness after cardiac resynchronization therapy for heart failure. Eur Heart J. 2006; 27: 1423–1430.
28. Steendijk P, Tulner SA, Bax JJ, Oemrawsingh PV, Bleeker GB, van Erven L, Putter H, Verwey HF, van der Wall EE, Schalij MJ. Hemodynamic effects of long-term cardiac resynchronization therapy: analysis by pressure-volume loops. Circulation. 2006; 113: 1295–1304.
29. Carson P, Anand I, O’Connor C, Jaski B, Steinberg J, Lwin A, Lindenfeld J, Ghali J, Barnet JH, Feldman AM, Bristow MR. Mode of death in advanced heart failure: the Comparison of Medical, Pacing, and Defibrillation Therapies in Heart Failure (COMPANION) trial. J Am Coll Cardiol. 2005; 46: 2329–2334.
30. Molhoek SG, Bax JJ, Bleeker GB, Holman ER, Van Erven L, Bootsma M, Boersma E, Steendijk P, Van Der Wall EE, Schalij MJ. Long-term follow-up of cardiac resynchronization therapy in patients with end-stage heart failure. J Cardiovasc Electrophysiol. 2005; 16: 701–707.[CrossRef][Medline] [Order article via Infotrieve]
31. Hoppe UC, Casares JM, Eiskjaer H, Hagemann A, Cleland JG, Freemantle N, Erdmann E. Effect of cardiac resynchronization on the incidence of atrial fibrillation in patients with severe heart failure. Circulation. 2006; 114: 18–25.
32. Kantharia BK, Patel JA, Nagra BS, Ledley GS. Electrical storm of monomorphic ventricular tachycardia after a cardiac-resynchronization-therapy-defibrillator upgrade. Europace. 2006; 8: 625–628.
33. Bortone A, Macia JC, Leclercq F, Pasquie JL. Monomorphic ventricular tachycardia induced by cardiac resynchronization therapy in patient with severe nonischemic dilated cardiomyopathy. Pacing Clin Electrophysiol. 2006; 29: 327–330.[CrossRef][Medline] [Order article via Infotrieve]
34. Voigt A, Barrington W, Ngwu O, Jain S, Saba S. Biventricular pacing reduces ventricular arrhythmic burden and defibrillator therapies in patients with heart failure. Clin Cardiol. 2006; 29: 74–77.[Medline] [Order article via Infotrieve]
35. Ermis C, Seutter R, Zhu AX, Benditt LC, VanHeel L, Sakaguchi S, Lurie KG, Lu F, Benditt DG. Impact of upgrade to cardiac resynchronization therapy on ventricular arrhythmia frequency in patients with implantable cardioverter-defibrillators. J Am Coll Cardiol. 2005; 46: 2258–2263.
36. Arya A, Haghjoo M, Dehghani MR, Alasti M, Alizadeh H, Kazemi B, Sadr-Ameli MA. Effect of cardiac resynchronization therapy on the incidence of ventricular arrhythmias in patients with an implantable cardioverter-defibrillator. Heart Rhythm. 2005; 2: 1094–1098.[CrossRef][Medline] [Order article via Infotrieve]
37. McSwain RL, Schwartz RA, DeLurgio DB, Mera FV, Langberg JJ, Leon AR. The impact of cardiac resynchronization therapy on ventricular tachycardia/fibrillation: an analysis from the combined Contak-CD and InSync-ICD studies. J Cardiovasc Electrophysiol. 2005; 16: 1168–1171.[CrossRef][Medline] [Order article via Infotrieve]
38. Saxon LA, Kerwin WF, Cahalan MK, Kalman JM, Olgin JE, Foster E, Schiller NB, Shinbane JS, Lesh MD, Merrick SH. Acute effects of intraoperative multisite ventricular pacing on left ventricular function and activation/contraction sequence in patients with depressed ventricular function. J Cardiovasc Electrophysiol. 1998; 9: 13–21.[Medline] [Order article via Infotrieve]
39. Ortale JR, Gabriel EA, Iost C, Marquez CQ. The anatomy of the coronary sinus and its tributaries. Surg Radiol Anat. 2001; 23: 15–21.[CrossRef][Medline] [Order article via Infotrieve]
40. Rossillo A, Verma A, Saad EB, Corrado A, Gasparini G, Marrouche NF, Golshayan AR, McCurdy R, Bhargava M, Khaykin Y, Burkhardt JD, Martin DO, Wilkoff BL, Saliba WI, Schweikert RA, Raviele A, Natale A. Impact of coronary sinus lead position on biventricular pacing: mortality and echocardiographic evaluation during long-term follow-up. J Cardiovasc Electrophysiol. 2004; 15: 1120–1125.[CrossRef][Medline] [Order article via Infotrieve]
41. Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002; 346: 877–883.
42. Bleeker GB, Schalij MJ, Van Der Wall EE, Bax JJ. Postero-lateral scar tissue resulting in non-response to cardiac resynchronization therapy. J Cardiovasc Electrophysiol. 2006; 17: 899–901.[CrossRef][Medline] [Order article via Infotrieve]
43. Ellenbogen KA, Kay N, Wilkoff B. Device Therapy for Congestive Heart Failure. Philadelphia, Pa: Elsevier, Inc; 2004: 118–231.
44. Leon AR. New tools for the effective delivery of cardiac resynchronization therapy. J Cardiovasc Electrophysiol. 2005; 16 (suppl 10): S42–S47.[CrossRef][Medline] [Order article via Infotrieve]
45. Singh JP, Fan D, Heist EK, Alabiad CR, Taub C, Reddy V, Mansour M, Picard MH, Ruskin JN, Mela T. Left ventricular lead electrical delay predicts response to cardiac resynchronization therapy. Heart Rhythm. 2006; 3: 1285–1292.[CrossRef][Medline] [Order article via Infotrieve]
46. Murphy RT, Sigurdsson G, Mulamalla S, Agler D, Popovic ZB, Starling RC, Wilkoff BL, Thomas JD, Grimm RA. Tissue synchronization imaging and optimal left ventricular pacing site in cardiac resynchronization therapy. Am J Cardiol. 2006; 97: 1615–1621.[CrossRef][Medline] [Order article via Infotrieve]
47. Woodard PK, Bhalla S, Javidan-Nejad C, Gutierrez FR. Non-coronary cardiac CT imaging. Semin Ultrasound CT MR. 2006; 27: 56–75.[CrossRef][Medline] [Order article via Infotrieve]
48. Vannan MA, Pedrizzetti G, Li P, Gurudevan S, Houle H, Main J, Jackson J, Nanda NC. Effect of cardiac resynchronization therapy on longitudinal and circumferential left ventricular mechanics by velocity vector imaging: description and initial clinical application of a novel method using high-frame rate B-mode echocardiographic images. Echocardiography. 2005; 22: 826–830.[CrossRef][Medline] [Order article via Infotrieve]
49. McAlister FA, Ezekowitz JA, Wiebe N, Rowe B, Spooner C, Crumley E, Hartling L, Klassen T, Abraham W. Systematic review: cardiac resynchronization in patients with symptomatic heart failure. Ann Intern Med. 2004; 141: 381–390.
50. Leon AR, Abraham WT, Curtis AB, Daubert JP, Fisher WG, Gurley J, Hayes DL, Lieberman R, Petersen-Stejskal S, Wheelan K. Safety of transvenous cardiac resynchronization system implantation in patients with chronic heart failure: combined results of over 2 000 patients from a multicenter study program. J Am Coll Cardiol. 2005; 46: 2348–2356.
51. Anh DJ, Chen HA, Eversull CS, Mourlas NJ, Mead RH, Liem LB, Hsia HH, Wang PJ, Al-Ahmad A. Early human experience with use of a deflectable fiberoptic endocardial visualization catheter to facilitate coronary sinus cannulation. Heart Rhythm. 2006; 3: 875–878.[CrossRef][Medline] [Order article via Infotrieve]
52. Rivero-Ayerza M, Thornton AS, Theuns DA, Scholten MF, Mekel JM, Res J, Jordaens LJ. Left ventricular lead placement within a coronary sinus side branch using remote magnetic navigation of a guidewire: a feasibility study. J Cardiovasc Electrophysiol. 2006; 17: 128–133.[CrossRef][Medline] [Order article via Infotrieve]
53. Schweikert RA, Saliba WI, Tomassoni G, Marrouche NF, Cole CR, Dresing TJ, Tchou PJ, Bash D, Beheiry S, Lam C, Kanagaratnam L, Natale A. Percutaneous pericardial instrumentation for endo-epicardial mapping of previously failed ablations. Circulation. 2003; 108: 1329–1335.
54. Navia JL, Atik FA, Grimm RA, Garcia M, Vega PR, Myhre U, Starling RC, Wilkoff BL, Martin D, Houghtaling PL, Blackstone EH, Cosgrove DM. Minimally invasive left ventricular epicardial lead placement: surgical techniques for heart failure resynchronization therapy. Ann Thorac Surg. 2005; 79: 1536–1544.
55. Gassis S, Leon AR. Cardiac resynchronization therapy: strategies for device programming, troubleshooting and follow-up. J Interv Card Electrophysiol. 2005; 13: 209–222.[CrossRef][Medline] [Order article via Infotrieve]
56. Ammann P, Sticherling C, Kalusche D, Eckstein J, Bernheim A, Schaer B, Osswald S. An electrocardiogram-based algorithm to detect loss of left ventricular capture during cardiac resynchronization therapy. Ann Intern Med. 2005; 142: 968–973.
57. Kashani A, Barold SS. Significance of QRS complex duration in patients with heart failure. J Am Coll Cardiol. 2005; 46: 2183–2192.
58. O’Donnell D, Nadurata V, Hamer A, Kertes P, Mohammed W. Long-term variations in optimal programming of cardiac resynchronization therapy devices. Pacing Clin Electrophysiol. 2005; 28 (Suppl 1): S24–S26.[CrossRef][Medline] [Order article via Infotrieve]
59. Yu CM, Wing-Hong Fung J, Zhang Q, Sanderson JE. Understanding nonresponders of cardiac resynchronization therapy: current and future perspectives. J Cardiovasc Electrophysiol. 2005; 16: 1117–1124.[CrossRef][Medline] [Order article via Infotrieve]
60. Birnie DH, Tang AS. The problem of non-response to cardiac resynchronization therapy. Curr Opin Cardiol. 2006; 21: 20–26.[Medline] [Order article via Infotrieve]
61. Hummel JP, Lindner JR, Belcik JT, Ferguson JD, Mangrum JM, Bergin JD, Haines DE, Lake DE, DiMarco JP, Mounsey JP. Extent of myocardial viability predicts response to biventricular pacing in ischemic cardiomyopathy. Heart Rhythm. 2005; 2: 1211–1217.[CrossRef][Medline] [Order article via Infotrieve]
62. Penicka M, Bartunek J, De Bruyne B, Vanderheyden M, Goethals M, De Zutter M, Brugada P, Geelen P. Improvement of left ventricular function after cardiac resynchronization therapy is predicted by tissue Doppler imaging echocardiography. Circulation. 2004; 109: 978–983.
63. Bax JJ, Ansalone G, Breithardt OA, Derumeaux G, Leclercq C, Schalij MJ, Sogaard P, St John Sutton M, Nihoyannopoulos P. Echocardiographic evaluation of cardiac resynchronization therapy: ready for routine clinical use? A critical appraisal. J Am Coll Cardiol. 2004; 44: 1–9.
64. Kerlan JE, Sawhney NS, Waggoner AD, Chawla MK, Garhwal S, Osborn JL, Faddis MN. Prospective comparison of echocardiographic atrioventricular delay optimization methods for cardiac resynchronization therapy. Heart Rhythm. 2006; 3: 148–154.[CrossRef][Medline] [Order article via Infotrieve]
65. Jansen AH, Bracke FA, van Dantzig JM, Meijer A, van der Voort PH, Aarnoudse W, van Gelder BM, Peels KH. Correlation of echo-Doppler optimization of atrioventricular delay in cardiac resynchronization therapy with invasive hemodynamics in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2006; 97: 552–557.[CrossRef][Medline] [Order article via Infotrieve]
66. Waggoner AD, Faddis MN, Gleva MJ, de las Fuentes L, Davila-Roman VG. Improvements in left ventricular diastolic function after cardiac resynchronization therapy are coupled to response in systolic performance. J Am Coll Cardiol. 2005; 46: 2244–2249.
67. van Gelder BM, Bracke FA, Meijer A, Lakerveld LJ, Pijls NH. Effect of optimizing the VV interval on left ventricular contractility in cardiac resynchronization therapy. Am J Cardiol. 2004; 93: 1500–1503.[CrossRef][Medline] [Order article via Infotrieve]
68. Vanderheyden M, De Backer T, Rivero-Ayerza M, Geelen P, Bartunek J, Verstreken S, De Zutter M, Goethals M. Tailored echocardiographic interventricular delay programming further optimizes left ventricular performance after cardiac resynchronization therapy. Heart Rhythm. 2005; 2: 1066–1072.[CrossRef][Medline] [Order article via Infotrieve]
69. Parreira L, Santos JF, Madeira J, Mendes L, Seixo F, Caetano F, Lopes C, Venancio J, Mateus A, Ines JL, Mendes M. Cardiac resynchronization therapy with sequential biventricular pacing: impact of echocardiography guided VV delay optimization on acute results. Rev Port Cardiol. 2005; 24: 1355–1365.[Medline] [Order article via Infotrieve]
70. Bordachar P, Lafitte S, Reuter S, Sanders P, Jais P, Haissaguerre M, Roudaut R, Garrigue S, Clementy J. Echocardiographic parameters of ventricular dyssynchrony validation in patients with heart failure using sequential biventricular pacing. J Am Coll Cardiol. 2004; 44: 2157–2165.
71. Baker J, McKenzie J, Beau S, Greer G, Porterfield J, Fedor M, Greenberg S, Daod E, Corbisiero R, Bailey J, Porterfield L. Acute evaluation of programmer guided AV/PV and VV delay optimization comparing an IEGM method and echocardiogram for cardiac resynchronization therapy in heart failure patients and dual chamber ICD implants. J Cardiovasc Electrophysiol. 2007: 18; 185–191.[CrossRef][Medline] [Order article via Infotrieve]
72. Bax JJ, Bleeker GB, Marwick TH, Molhoek SG, Boersma E, Steendijk P, van der Wall EE, Schalij MJ. Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy. J Am Coll Cardiol. 2004; 44: 1834–1840.
73. Turner MS, Bleasdale RA, Vinereanu D, Mumford CE, Paul V, Fraser AG, Frenneaux MP. Electrical and mechanical components of dyssynchrony in heart failure patients with normal QRS duration and left bundle-branch block: impact of left and biventricular pacing. Circulation. 2004; 109: 2544–2549.
74. Egoavil CA, Ho RT, Greenspon AJ, Pavri BB. Cardiac resynchronization therapy in patients with right bundle branch block: analysis of pooled data from the MIRACLE and Contak CD trials. Heart Rhythm. 2005; 2: 611–615.[CrossRef][Medline] [Order article via Infotrieve]
75. Aranda JM Jr, Conti JB, Johnson JW, Petersen-Stejskal S, Curtis AB. Cardiac resynchronization therapy in patients with heart failure and conduction abnormalities other than left bundle-branch block: analysis of the Multicenter InSync Randomized Clinical Evaluation (MIRACLE). Clin Cardiol. 2004; 27: 678–682.[Medline] [Order article via Infotrieve]
76. Fantoni C, Kawabata M, Massaro R, Regoli F, Raffa S, Arora V, Salerno-Uriarte JA, Klein HU, Auricchio A. Right and left ventricular activation sequence in patients with heart failure and right bundle branch block: a detailed analysis using three-dimensional non-fluoroscopic electroanatomic mapping system. J Cardiovasc Electrophysiol. 2005; 16: 112–119;discussion 120–121.[CrossRef]
77. Eldadah ZA, Rosen B, Hay I, Edvardsen T, Jayam V, Dickfeld T, Meininger GR, Judge DP, Hare J, Lima JB, Calkins H, Berger RD. The benefit of upgrading chronically right ventricle-paced heart failure patients to resynchronization therapy demonstrated by strain rate imaging. Heart Rhythm. 2006; 3: 435–442.[CrossRef][Medline] [Order article via Infotrieve]
78. Horwich T, Foster E, De Marco T, Tseng Z, Saxon L. Effects of resynchronization therapy on cardiac function in pacemaker patients "upgraded" to biventricular devices. J Cardiovasc Electrophysiol. 2004; 15: 1284–1289.[CrossRef][Medline] [Order article via Infotrieve]
79. van Oosterhout MF, Prinzen FW, Arts T, Schreuder JJ, Vanagt WY, Cleutjens JP, Reneman RS. Asynchronous electrical activation induces asymmetrical hypertrophy of the left ventricular wall. Circulation. 1998; 98: 588–595.
80. Adomian GE, Beazell J. Myofibrillar disarray produced in normal hearts by chronic electrical pacing. Am Heart J. 1986; 112: 79–83.[CrossRef][Medline] [Order article via Infotrieve]
81. Prinzen FW, Peschar M. Relation between the pacing induced sequence of activation and left ventricular pump function in animals. Pacing Clin Electrophysiol. 2002; 25: 484–498.[CrossRef][Medline] [Order article via Infotrieve]
82. Ichiki H, Oketani N, Hamasaki S, Ishida S, Kataoka T, Ogawa M, Saihara K, Okui H, Fukudome T, Shinasato T, Kubozono T, Ninomiya Y, Matsushita T, Otsuji Y, Tei C. Effect of right ventricular apex pacing on the Tei index and brain natriuretic peptide in patients with a dual-chamber pacemaker. Pacing Clin Electrophysiol. 2006; 29: 985–990.[CrossRef][Medline] [Order article via Infotrieve]
83. Al-Hesayen A, Parker JD. Adverse effects of atrioventricular synchronous right ventricular pacing on left ventricular sympathetic activity, efficiency, and hemodynamic status. Am J Physiol Heart Circ Physiol. 2006; 291: H2377–H2379.
84. Tops LF, Schalij MJ, Holman ER, van Erven L, van der Wall EE, Bax JJ. Right ventricular pacing can induce ventricular dyssynchrony in patients with atrial fibrillation after atrioventricular node ablation. J Am Coll Cardiol. 2006; 48: 1642–1648.
85. Wilkoff BL, Cook JR, Epstein AE, Greene HL, Hallstrom AP, Hsia H, Kutalek SP, Sharma A. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA. 2002; 288: 3115–3123.
86. Sweeney MO, Hellkamp AS, Ellenbogen KA, Greenspon AJ, Freedman RA, Lee KL, Lamas GA. Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation. 2003; 107: 2932–2937.
87. Higgins SL, Hummel JD, Niazi IK, Giudici MC, Worley SJ, Saxon LA, Boehmer JP, Higginbotham MB, De Marco T, Foster E, Yong PG. Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias. J Am Coll Cardiol. 2003; 42: 1454–1459.
88. Abraham WT, Young JB, Leon AR, Adler S, Bank AJ, Hall SA, Lieberman R, Liem LB, O’Connell JB, Schroeder JS, Wheelan KR. Effects of cardiac resynchronization on disease progression in patients with left ventricular systolic dysfunction, an indication for an implantable cardioverter-defibrillator, and mildly symptomatic chronic heart failure. Circulation. 2004; 110: 2864–2868.
89. Leclercq C, Victor F, Alonso C, Pavin D, Revault d’Allones G, Bansard JY, Mabo P, Daubert C. Comparative effects of permanent biventricular pacing for refractory heart failure in patients with stable sinus rhythm or chronic atrial fibrillation. Am J Cardiol. 2000; 85: 1154–1156.[CrossRef][Medline] [Order article via Infotrieve]
90. Leon AR, Greenberg JM, Kanuru N, Baker CM, Mera FV, Smith AL, Langberg JJ, DeLurgio DB. Cardiac resynchronization in patients with congestive heart failure and chronic atrial fibrillation: effect of upgrading to biventricular pacing after chronic right ventricular pacing. J Am Coll Cardiol. 2002; 39: 1258–1263.
91. Molhoek SG, Bax JJ, Bleeker GB, Boersma E, van Erven L, Steendijk P, van der Wall EE, Schalij MJ. Comparison of response to cardiac resynchronization therapy in patients with sinus rhythm versus chronic atrial fibrillation. Am J Cardiol. 2004; 94: 1506–1509.[CrossRef][Medline] [Order article via Infotrieve]
92. Kay GN, Ellenbogen KA, Giudici M, Redfield MM, Jenkins LS, Mianulli M, Wilkoff B. The Ablate and Pace Trial: a prospective study of catheter ablation of the AV conduction system and permanent pacemaker implantation for treatment of atrial fibrillation. APT Investigators. J Interv Card Electrophysiol. 1998; 2: 121–135.[CrossRef][Medline] [Order article via Infotrieve]
93. Natale A, Zimerman L, Tomassoni G, Newby K, Leonelli F, Fanelli R, Beheiry S, Pisano E. AV node ablation and pacemaker implantation after withdrawal of effective rate-control medications for chronic atrial fibrillation: effect on quality of life and exercise performance. Pacing Clin Electrophysiol. 1999; 22: 1634–1639.[CrossRef][Medline] [Order article via Infotrieve]
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||