Tissue Doppler imaging in patients with congestive heart failure and conduction disorders

Abstract

Resynchronization of segmental left ventricular mechanics as well as re-coordination of both atrio-ventricular and inter-ventricular contraction are potential mechanisms responsible for the clinical benefit observed in patients with advanced congestive heart failure treated by cardiac resynchronization therapy (CRT). Initially electrical conduction problems, in the majority of cases a left bundle branch block (LBBB), were considered the target for CRT. However, growing experience with CRT in different patient populations including those with only a mild degree of conduction disturbance, and improved cardiac imaging utilizing the tissue Doppler approach have shown the complexity of CRT and the usefulness of sophisticated echocardiographic imaging techniques for therapeutic decision making.

List of abbreviations and acronyms

List of abbreviations and acronyms
 
• CHF

  congestive heart failure

 
• CRT

  cardiac resynchronization therapy

 
• DCM

  dilated cardiomyopathy

 
• EF

  ejection fraction

 
• EMD

  electromechanical delay

 
• HCM

  hypertrophic cardiomyopathy

 
• LBBB

  left bundle branch block

 
• LV

  left ventricle/ventricular

 
• MR

  mitral regurgitation

 
• RV

  right ventricle/ventricular

 
• TDE

  tissue Doppler echocardiography

Clinical impact of CRT in severe heart failure

Cardiac resynchronization therapy (CRT) has evolved as a non-pharmacological treatment option for patients with advanced congestive heart failure (CHF), impaired left ventricular (LV) systolic function, and intraventricular conduction abnormalities. Several studies have documented clinical improvement after both short- and longer-term follow-up. Global clinical benefit, i.e., improvement of NYHA functional class, 6 min walking distance, peak oxygen consumption, and a decrease in re-hospitalization for CHF has been repeatedly documented. These findings are generally accompanied by improvement of cardiac function, i.e., reduced LV dilatation, decrease of secondary mitral regurgitation, increase in LV contractility and ejection fraction, and improvement of myocardial energy balance.^1–11 The term “reverse LV remodeling” has been proposed to describe these long-term effects of CRT on cardiac function and geometry.

The beneficial effects of CRT have prompted inclusion of this new therapeutic option into the current guidelines for CHF management.¹² The “ideal” candidate for CRT is likely a patient with non-ischemic dilated cardiomyopathy in sinus rhythm with a left bundle branch block (LBBB) and a QRS duration of >150 ms. Nevertheless, patients with ischemic cardiomyopathy or other causes of CHF, with atrial fibrillation, other types, and less severe conduction delays have also been treated successfully by CRT.^13–15

Selection of CRT candidates: QRS width, invasive testing, or what else?

Cardiac dyssynchrony may manifest as impaired atrio-ventricular, inter- (RV–LV) ventricular, or segmental intra- (LV) ventricular coordination. The electrical phenomenon of QRS widening or a bundle branch block pattern may thus be used as marker for cardiac dyssynchrony but does not reflect the full spectrum of findings. However, most of the early work done in the field of CRT has focused on the deleterious effects of a wide LBBB, and narrowing of the QRS complex was considered the major target.^4–6,15

With increasing experience it became apparent that the clinical effect of CRT was not necessarily correlated with the degree of QRS shortening. Atrio-bi- and atrio-left ventricular pacing, the latter often associated with an increase in QRS width, have yielded comparably positive clinical results. Furthermore, the QRS width taken as inclusion criterion for CRT ranged from 120 to >150 ms among published studies. It remains yet unclear whether a classical LBBB morphology is required or not, or which LV region should be targeted for lead placement.^16–20

Based on the experience of the PATH-CHF studies, some centers suggested routine acute hemodynamic testing with probatory stimulation from various LV regions using different cardiac veins and different atrioventricular delays,²⁰ restricting definitive pacemaker implantation to acute hemodynamic responders, i.e., patients with a certain rise in contractility parameters like pulse pressure or dp/dt. Furthermore, it has been shown that modulation of contraction by pacing may be detrimental if performed in an inappropriate clinical situation, or if the “wrong” site of the LV is pre-excited,²¹ resulting in further “de-synchronization” of cardiac mechanics. However, it remains uncertain whether an acute hemodynamic response of LV contractility predicts the success of chronic stimulation. It may be remembered that acute hemodynamic testing was unreliable in predicting the long-term effect of sequential atrio-RV pacing to abolish LV outflow obstruction in hypertrophic cardiomyopathy, a situation that might be characterized as “de-synchronization”^22,23 of the hyperkinetic LV typical for this entity.

There is thus a need for reliable, at best non-invasive tools that allow for a better characterization of the electro-mechanical cardiac events on atrio-ventricular, right-left ventricular, and regional intra-left ventricular level in potential CRT candidates. Such a testing tool should also enable us to assess if and how cardiac “re-synchronization” by pacing may be achieved.

Echocardiographic assessment of cardiac dyssynchrony at baseline

Analysis of the activation–contraction sequence by echocardiographic imaging, focusing on all aspects of cardiac dyssynchrony, may be a reasonable approach in CHF patients with conduction abnormalities. Standard M-mode and two-dimensional echocardiographic techniques, conventional flow Doppler, and tissue Doppler methods have all been employed to analyze right and left ventricular function and interaction. Among these ultrasound techniques, tissue Doppler echocardiography (TDE) has gained popularity due to its potential to non-invasively analyze the LV activation–contraction sequence on a regional basis²⁴ with high spatial (<1 mm) and temporal (>100 Hz) resolution. We and other groups have adopted this technique which has an increasing impact on the indication for CRT.^25–38

In a study based on TDE analysis of regional longitudinal LV function in normals as opposed to patients with different etiologies of CHF and a QRS complex of >140 ms²⁵ we were able to demonstrate different patterns of LV dyssynchrony: 2/3 of the CHF patients had intra-LV dyssynchrony with the lateral LV wall moving latest, while in the other 1/3 just the opposite was found. Furthermore, despite the substantial QRS widening, 12% of these patients had no detectable dyssynchrony exceeding the limit that was also found in normals with an intra-LV delay of >30 ms (Fig. 1). Intra-LV asynchrony was not correlated with inter-ventricular dyssynchrony in this population. Yu et al.³⁶ also utilizing tissue Doppler assessment, found LV systolic and diastolic mechanical dyssynchrony to be common also in CHF patients with a narrow QRS complex. These findings suggest that mechanical LV dyssynchrony at baseline does not parallel the degree of conduction disturbance, and that various types of mechanical dyssynchrony may have identical ECG patterns.

Tissue Doppler based assessment of LV dyssynchrony and CRT success

Utilizing tissue Doppler based echocardiographic measures of cardiac dyssynchrony, Yu et al.¹¹ demonstrated improvement of LV synchronicity and cardiac function within three months of CRT. When CRT was turned off, all parameters deteriorated to baseline values. In a tissue Doppler imaging study of patients treated with CRT for idiopathic DCM and a QRS width >120 ms, Bax et al.³⁸ also demonstrated a reduction of the delay between septum and free wall in reaching peak systolic velocity. Using a protocol similar to ours,²⁵ Schuster et al.³⁴ studied 18 patients at baseline and one month after CRT, and demonstrated a more synchronous longitudinal LV movement pattern during CRT. Søgaard et al.³⁰ reported TDE-assessed improvement of regional LV dyssynchrony to be associated with significant reverse LV remodeling. They found the degree of mechanical dyssynchrony at baseline being the best predictor of long-term CRT success. The same group³² used a TDE-based technique to steer lead placement, and in order to decide whether to activate the two ventricles simultaneously or sequentially.

We studied 76 CHF patients²⁵ selected for CRT by the following criteria: QRS width ⩾150 ms, and positive response to probatory stimulation during invasive hemodynamic testing²⁰. All patients underwent comprehensive echocardiographic imaging focusing on the various aspects of cardiac (i.e., atrio-ventricular, inter-ventricular and intra-LV) dyssynchrony, and looking at regional electromechanical delays (EMDs) at baseline and 6±4 months after device implantation. Patients were then followed for approximately two years by serial 2D echocardiography. TDE demonstrated mechanical LV resynchronization in only 60% of these patients (Fig. 2). The same percentage had a significant reverse LV remodeling effect (Fig. 3) during long-term follow-up (21±6 months) of CRT, closely correlated to mechanical resynchronization. Although improvement of cardiac function and decrease of LV size was large enough to make the entire cohort significantly better, these benefits were largely limited to the “TDE responders” (Fig. 4).

Echocardiographic imaging including the tissue Doppler approach is thus a valuable tool for the assessment of CRT candidates at baseline and for verification of CRT effects during follow-up. Unfortunately, consensus on which TDE measurements should be used, and where to place the regions of interest, has not yet been achieved. Among the various groups that have studied tissue Doppler in the CRT context, at least three different approaches for the assessment of intra-LV dyssynchrony have been proposed (Fig. 5). Results may be completely different utilizing either of these approaches.

While the method used by Søgaard et al. focuses on late- or post-systolic longitudinal motion towards the transducer (“contraction”), Yu et al. looked at regional differences between the interval from QRS onset to peak systolic velocity. Both groups assessed both basal and middle LV segments in a 12-segment model. On the other hand, our and Schuster's approach analyzes the basal LV in two orthogonal planes (anterio-posterior and septal-lateral), and focuses on early systole, measuring the regional difference between the onset of the QRS complex and the onset of systolic movement. Furthermore, it has been argued that deformation (i.e., strain and strain-rate) imaging, although based on tissue Doppler data as well, may be a superior technique due to its ability to separate passive movements, which might result from tethering by adjacent regions, from active shortening or lengthening of a given myocardial region.³⁵

Conclusions

The assessment of cardiac mechanics by echocardiographic techniques that are able to provide the temporal and spatial resolution necessary to study segmental LV dyssynchrony appears to be useful for both identifying potential long-term responders of CRT and quantifying the effect of CRT. The degree or pattern of QRS prolongation as well as invasive hemodynamic testing procedures with probatory stimulation have not shown so far to reliably identify patients who will have a long-term benefit from CRT. However, further research is needed to define which of the different TDE-based measurements best defines intra-LV dyssynchrony at baseline, may be used to steer lead placement in order to improve the CRT results, and is most helpful during follow-up. Ongoing studies are intended to develop such a tissue Doppler-based marker of LV dyssynchrony.

References