doi: 10.1161/CIRCULATIONAHA.105.607366
(Circulation. 2006;113:926-928.)
© 2006 American Heart Association, Inc.
Editorial |
Quest for the Best Candidate
How Much Imaging Do We Need Before Prescribing Cardiac Resynchronization Therapy?
From I. Medizinische Klinik, Klinikum Mannheim gGmbH, Faculty of Clinical Medicine Mannheim at the University of Heidelberg, Mannheim, Germany (O.-A.B.); and Medizinische Klinik und Poliklinik C, Westfälische-Wilhelms-Universität Münster, Münster, Germany (G.B.).
Correspondence to Priv-Doz Dr med Ole-A. Breithardt, I. Medizinische Klinik, Klinikum Mannheim gGmbH, Theodor-Kutzer-Ufer 1–3, D-68167 Mannheim, Germany. E-mail ole.breithardt{at}med.ma.uni-heidelberg.de
Key Words: Editorials • echocardiography • heart failure • magnetic resonance imaging • pacing
Within the last decade, cardiac resynchronization therapy (CRT) has evolved rapidly and is today widely accepted as a class I indication for selected patients with heart failure.1,2 It is generally recommended for patients with advanced systolic heart failure who are symptomatic despite optimized pharmacological treatment and who show evidence of ventricular dyssynchrony, usually diagnosed by a prolongation of the QRS width above 120 to 130 ms. Devices that combine biventricular pacing with an implantable defibrillator (CRT-D) have demonstrated a significant reduction in arrhythmic death in a high-risk population.3,4 The more recently published results from the Cardiac Resynchronization-Heart Failure (CARE-HF) trial showed a significant survival benefit for such selected patients who were treated with a biventricular CRT pacemaker device (CRT-P) without defibrillator backup.5 These beneficial CRT effects in addition to optimized pharmacological therapy result in a strikingly reduced need for heart failure–related hospitalization and make CRT-P clearly a cost-effective therapy, with an incremental cost-effectiveness ratio of less than &$25.000 per quality-adjusted life-year gained.6–8 At present, however, the majority of implanted systems in the United States and in Western Europe are CRT-D devices, which, in comparison to CRT-P, offer only a comparatively modest additional survival benefit in relation to their incremental costs.9 Therefore, these CRT-D devices must currently be regarded as less cost-effective than CRT-P, and there is an ongoing debate as to whether every patient qualifying for CRT should receive a CRT-D device.10,11 From a cardiologist’s point of view, the decision about the need for a defibrillator backup should only be based on a careful assessment of the individual risk for sudden death and each patient’s (estimated) individual survival benefit and not by our concerns about general healthcare expenditures. If we want to keep the freedom to prescribe the best treatment for each patient, however, we will have to improve cost-effectiveness. To achieve this ambitious goal, it is necessary to improve the patient selection process because, unlike any pharmacological therapy, most of the CRT-related costs originate at the time of implantation. In terms of cost-effectiveness, it will be too late to identify the nonresponding patients after device implantation. At this point in time, one might try to improve the clinical response by individual optimization of the stimulation settings and to evaluate whether other measures such as lead repositioning might be required. However, the costs for the device and the implantation procedure cannot be revoked any more, and some unfortunate patients may have implantation-related intricacies without any long-term benefit from the CRT device. Thus, the optimal strategy to improve cost-effectiveness must focus on a better patient selection to reduce the number of unnecessary implants and clinical nonresponders.
Articles pp 960 and 969
Numerous studies have been published in the past few years that evaluated different strategies to identify the presence of mechanical dyssynchrony and other clinical predictors for long-term improvement.12 There is today a general consensus that the QRS width is not precise enough to define the presence of mechanical ventricular dyssynchrony.13 Dyssynchronous contraction patterns contribute independent of the intrinsic myocellular damage to the hemodynamic deterioration in patients with advanced systolic heart failure and form the pathophysiological basis to justify prescription of CRT. Although we are waiting for prospective data from ongoing randomized trials that evaluate the use of direct markers for assessment of mechanical dyssynchrony,14 however, current guidelines must still refer to QRS width as the main selection criterion to identify suitable CRT patients.1,2
Two articles in the present issue of Circulation make use of cardiac imaging modalities that are technically very different but provide important complementary information to improve patient stratification before prescribing CRT: Bleeker et al15 focused on the presence and the regional extent of myocardial scar tissue identified by contrast-enhanced cardiac magnetic resonance imaging (MRI), and Suffoletto et al16 evaluated the role of "2D strain" echocardiography, a novel, innovative echocardiographic technique for quantification of ventricular dyssynchrony.
Bleeker et al15 picked contrast-enhanced cardiac MRI as the current clinical gold standard for the identification of scar tissue. They selected patients with documented coronary artery disease, defined by a >50% diameter stenosis of at least 1 coronary artery and compared the clinical CRT response at 6-month follow-up between patients with and those without myocardial scar tissue in the posterolateral region. It was clearly demonstrated that clinical CRT nonresponders are more likely to have a previous myocardial infarction with a transmural scar in the posterolateral region, the typical target region for left ventricular (LV) pacing in CRT. This alone would have been an important message to report, but the authors did not settle and went one step further: They also looked carefully for ventricular dyssynchrony by tissue Doppler imaging (TDI). Based on previous observations by the same group, a septal-lateral delay in the time to regional peak systolic velocity of more then 65 ms was used as a cutoff to define patients with clinically relevant ventricular dyssynchrony.17 It is of particular interest to note that 11 of 14 patients (78%) with a transmural scar in the posterolateral region showed significant dyssynchrony by TDI, but only 2 of 11 (19%) responded well to CRT after 6 months. In the remainder, the degree of dyssynchrony was not affected by LV-based pacing.
With the current technology, TDI is an almost perfect screening tool to identify the presence of dyssynchrony during a routine echocardiographic examination and has a key position in patient stratification before CRT and during follow-up.12,18 However, it obviously cannot answer all questions, and the observation that the degree of ventricular dyssynchrony by the septal-lateral delay was similar in patients with and without scars points to a well-known limitation of the velocity-based TDI analysis. Segmental myocardial motion as measured by the peak systolic velocity does not indicate whether a segment is actively contracting or whether it moves passively as a result of active contraction in neighboring segments.19 Thus, such a simple TDI velocity analysis can neither replace an endocardial mapping study to define the sequence of electrical activation nor reliably identify the true sequence of myocardial deformation20 or differentiate between viable and nonviable segments, unless the velocity profile throughout the complete cardiac cycle is analyzed in a stress test.21
One might assume that CRT is ineffective in patients with posterolateral scars, because the LV lead is placed in a region were it is not able to stimulate viable myocardium. However, this is contradicted by the fact that the measured sensing and pacing values at implantation did not differ between the groups. Thus, it cannot be the lack of pacing but rather pacing in the wrong position that accounts for the lack in clinical improvement. Because the implanters, blinded to the MRI results, attempted to position the LV lead in the generally recommend posterolateral region, they might have been forced to choose a very proximal (basal) or distal (apical) position in the coronary sinus tributaries to ensure adequate pacing thresholds. Particularly in patients with previous myocardial infarctions, the functional line of block and the latest site of ventricular activation can be very heterogeneously distributed.22 Thus, the attempts to ensure effective LV stimulation might result in a suboptimal position of the electrodes, not corresponding well to the site of latest activation. This issue is not answered in the article by Bleeker et al15 and warrants further analysis.
Such an attempt to correlate the position of the LV pacing lead to ventricular dyssynchrony and the actual site of latest myocardial deformation was made in the study by Suffoletto et al.16 The authors tested a novel technique for noninvasive quantification of myocardial deformation, based on the analysis of gray-scale speckle information (2D strain).23 In contrast to TDI-derived strain rate imaging data, 2D strain has less temporal resolution but the theoretical advantage of being angle-independent, which allows one to obtain data on radial and circumferential deformation from all segments, similar to MRI tagging. The results demonstrate that the 2D strain analysis from a midventricular parasternal short-axis view appears to be feasible in more than 90% of the attempted analyses. They could also show that 2D strain correlates well to conventional TDI-derived radial strain and that it provides clinically meaningful information about the site of latest myocardial deformation, which might be used in the future to identify the optimal lead position for CRT. The study by Suffoletto et al16 is limited by the fact that the authors focused on a single view with only 6 midventricular segments. This might not be appropriate to characterize the deformation sequence precisely, but it may provide enough information for the clinical routine. It is not clear yet which direction of myocardial deformation is more important (or more reliable) to characterize dyssynchrony: the radial direction, the longitudinal direction, or both. Future studies will have to look further at the basal and apical segments and compare longitudinal, radial, and circumferential deformation.
The results of both studies are straightforward and do not come unexpected: Patients who show evidence of dyssynchrony and viable myocardium are more likely to benefit from CRT than those with synchronous contraction or previous myocardial infarctions with transmural scars,15 in particular when the LV lead is placed close to the site of latest activation (deformation).16 What does this information add to our understanding of CRT? How will it affect our clinical routine? Should we perform a cardiac MRI in every patient with coronary artery disease? How will a myocardial infarction in the septum or anterior wall affect the CRT response? Do we have to perform strain studies in everyone? Obviously, additional investigations make sense before implanting a CRT device, including cardiac MRI and advanced echocardiography. At first glance, these additionally required investigations appear to complicate our pre-CRT patient stratification and make it more time-consuming and costly. It is tempting to stick solely to the QRS complex to identify CRT candidates; however, we have learned in recent years that this simple-minded approach will result in a significant number of unsuccessful implants and keep the overall costs high. To improve the cost-effectiveness of heart failure device therapy, we must improve the patient selection process with intelligent and flexible diagnostic algorithms. This clearly also requires a foresighted investment in new imaging technologies, from portable echocardiography to advanced echocardiographic techniques and cardiac MRI. We now know that we can do better!
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Acknowledgments |
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Disclosures
Dr O.-A. Breithardt received speakers honoraria from Medtronic, Guidant, and GE Vingmed. Dr G. Breithardt received speaker’s honoraria from Medtronic and Guidant.
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Footnotes |
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The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
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