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The selection of patients for cardiac resynchronization therapy

Daniel Gras*, Jean Pierre Cebron, Philippe Brunel, Bernard Leurent and Yves Banus

Unité de soins et de cardiologie interventionnelle, Nouvelles Cliniques Nantaises, Nantes, France

Received 3 May 2004; accepted 24 May 2004.

* Daniel Gras, MD, Unité de soins et de cardiologie interventionnelle, Nouvelles Cliniques Nantaises, 4, Rue Eric Tabarly 44277 Nantes, Cedex 2, France. Tel.: +33-228-255-115; fax: +33-228-255117
dangras{at}aol.com

Abstract

This paper is intented to summarize our present knowledge on which patients will profit from cardiac resynchronisation therapy.

Key Words: Cardiac resynchronization therapy

Despite remarkable advances, pharmacological treatment of heart failure suffers serious limitations, as does, when all else has failed, cardiac transplantation. ß-Blocker therapy, which is now widely accepted as an effective treatment, may only be used in up to two third of the patients suffering from heart failure symptoms. In this context, cardiac resynchronization therapy (CRT) has recently been introduced with, as a first objective, the relief of cardiac symptoms refractory to optimal medical therapy.1–4 Acute hemodynamic studies first demonstrated that CRT could improve left ventricular mechanical function, increase cardiac index, and decrease pulmonary artery pressures.5–8 These favorable effects were associated with a decrease in myocardial oxygen consumption,9 indicating a reorganization of the segmental left ventricular contraction sequence and ultimately an improved global ventricular function, instead of an increase in contractility at a cellular level.

Recent results of the MUSTIC and MIRACLE trials10–12 are consistent in showing an improvement of NYHA functional class, of quality of life scores, and of the distance covered during a 6-minute walk. Positive impact on left ventricular function indexes was also reported, as demonstrated by a decrease in dynamic mitral regurgitation, an increase in global ejection fraction and a reverse remodeling effect. The latter is usually delayed over time, with an optimal effect observed 3–6 months after CRT. Such benefit can not be evaluated during an acute hemodynamic study, which could potentially misclassify patients likely to respond to CRT only after some time. Finally, a reduction in hospitalization rate and duration was documented and could further positively impact on health care-related costs.

These positive results may only be obtained in carefully selected patients (Table 1), currently those with a cardiomyopathy, evidenced by a left ventricular end diastolic diameter 55 mm and global ejection fraction 35%, either of ischemic or non ischemic origin.12 As the primary goal of CRT was to improve cardiac symptoms, potential candidates are supposed to be in NYHA functional class III or IV. However, this particular point remains to be further evaluated, as some patients in functional class II could also benefit from the therapy over a longer period of time.


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  		Table 1 Selecting criteria for CRT

 
Individual diagnosis of ventricular dysynchrony is another key parameter before considering CRT, since it is what the treatment intends to remedy. In other terms, patients without ventricular dysynchrony are not expected to derive any clinical benefit, and consequently, are not yet considered candidates for this treatment option. A first criterion to define ventricular dysynchrony was based on a QRS duration, with different values considered from 120 to 150 ms1–4,10,12 depending on authors' definition. Despite its easy and non invasive evaluation on surface ECG, this electrical approach suffers from a lack of clear correlation with the mechanical aspect of dysynchrony, therefore leading to misdiagnose potential responders in a subgroup of patients with short or normal QRS duration.

The link between cardiac dysynchrony and ventricular conduction disturbances on the ECG is indeed not straightforward, and the precise value of QRS duration on which we could rely to assess ventricular dysynchrony remains uncertain. This could be explained by the limited information provided by conventional ECG, which does not explore the three-dimensional nature of the electrical disorder. Nevertheless, the larger the QRS the more likely is ventricular dysynchrony. On the other hand, an extra large QRS duration may sometimes correlate with a very severe disease, where the natural process is too advanced to expect any reverse benefit. In the later, the indication for CRT could become questionable, despite all classical criteria for selecting a potential responder are fulfilled.

Both patients presenting with a left or a right bundle branch block aspect, are reported to be clinically improved during CRT.12 However, in some situations, the right bundle branch block may traduce a severe right ventricular disease, which natural course can not always be reversed by CRT.

Considering the limitations of conventional ECG, echocardiographic parameters were recently proposed to investigate the presence of ventricular dysynchrony.7,8,13,14 Such parameters intend to investigate the mechanical consequences of ventricular conduction disorders. In the ongoing CARE-HF study,15 ventricular dysynchrony is assessed by echocardiography (Table 2) in patients with little increase in QRS duration (120–150 ms), by considering respectively (1) a prolonged aortic pre-ejection delay (140 ms), (2) an increase mechanical interventricular delay (40 ms) and (3) a left ventricular segmental post systolic contraction.


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  		Table 2 Evaluation of ventricular dysynchrony in Care-HF Trial

 
The aortic pre-ejection delay is measured between the onset of QRS complex and the beginning of the aortic flow by pulsed wave Doppler. Prolongation in this delay is explained by a delayed left ventricular contraction due to conduction disorders. Together with the prolongation in left ventricular contraction duration, this further translates in a decrease of left ventricular filling duration. The latter is related to a delayed early diastolic filling, which ultimately results in a fusion between early and late diastolic filling, as demonstrated by a unique transmitral flow on pulsed wave Doppler. A simple rule may be expressed here: the longer the aortic pre-ejection delay, the shorter the left ventricular filling duration, the more advanced is ventricular dysynchrony.

The mechanical interventricular delay is evaluated during pulsed wave Doppler, by the time difference between the onset of the pulmonary flow and the aortic flow. Prolongation in this delay is explained by the loss of coordination in septal activation and contraction. This results in a decrease in regional ejection fraction, therefore contributing for a lower left ventricular global ejection fraction.

The left ventricular segmental post systolic contraction is defined as the maximal local wall inward movement (local peak contraction), using either M-mode or tissue Doppler echo, occurring later than the start of the transmitral Doppler flow signal. Caution is required to well distinguish passive movement from active local contraction. Such phenomenon is usually documented at the left ventricular posterolateral wall, arguing to consider a lateral or posterior coronary sinus tributaries in order to pace the left ventricular from this particular region.16,17 This particular anomaly may have serious hemodynamic consequences. First, this deteriorates the left ventricular systolic function through a lack of coordination in left ventricular segmental contraction. Second it impairs left ventricular filling because of delayed local relaxation. Third, this may contribute to functional mitral regurgitation, caused by a delayed contraction of the papillary muscles, which, in turn, results in a lack of synchronicity in mitral leaflets closure.

Previous selective parameters allowed to identify 70–80% of CRT responders.10,12 However, absence of clinical benefit may be observed in patients appropriately selected, due to non optimal lead positioning, in particular when the left ventricular electrode is placed within a great cardiac vein (Fig. 1). Lack of response may also be related to the occurrence of various types of arrhythmia (atrial, ventricular or electronic), therefore responsible for transient CRT delivery, and finally for a waste of the expected treatment efficacy. Additional parameters are still required to better investigate abnormal coordination in segmental left ventricular contraction, in a way to optimize selection of patients likely to benefit from CRT. This will probably be achieved with the further development of specific tools, using mainly Tissue Doppler imaging techniques, dedicated to a more appropriate and more automatic diagnosis of ventricular dysynchrony.



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  		Fig. 1 In appropriately selected patients, leads positioning remain of key importance to reach successful cardiac resynchronization therapy. (a) Right ventricular lead is first implanted and placed closed to the mid interventricular septum, in order to avoid pacing at the apex. After right atrial lead placement, venography is performed, showing here a lateral vein of good caliber (arrow) with no major obstacles for catheterization. (b) Left ventricular lead is implanted in the targeted lateral vein (arrow). Using anteroposterior plane both ventricular leads appear to be anatomically close. (c) LAO view 40° demonstrates that left ventricular lead is well placed in the posterior lateral left ventricular region, anatomically far from the right ventricular lead. This view is also helpful to check the appropriate positioning of the right ventricular lead, at the mid interventricular septum.

 
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