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Cardiac resynchronisation therapy: what any clinician should know

An article from the e-journal of the ESC Council for Cardiology Practice

An overwhelming amount of evidence from prospective randomised controlled trials supports the clinical efficacy and safety of cardiac resynchronisation therapy (CRT) in patients with drug-refractory severely symptomatic heart failure and ventricular dyssynchrony. CRT makes heart failure patients feel better, improves cardiac structure and function, and (hopefully) prolongs survival in some peculiar subset of patients. Since CRT is not for all heart failure patients, those who can potentially benefit need to be carefully identified.

Heart Failure (HF)


Rationale

Patients with left ventricular (LV) systolic dysfunction and dilatation frequently have ventricular conduction delays. This is usually manifested as a left bundle branch block (LBBB), but it often occurs in patients with narrow QRS also. This type of conduction abnormality is generally associated with delayed depolarisation and contraction of the lateral LV free wall (ventricular dyssynchrony). Ventricular dyssynchrony  might contribute to disease progression. 
CRT can resynchronise the ventricular activation pattern by acting as an electrical bypass, thus restoring a more coordinated ventricular contraction, by two main mechanisms: pre-exciting the LV lateral wall with atrial-synchronous left or biventricular pacing and shortening or optimising the atrio-ventricular interval. Pre-excitation of the LV lateral wall allows a more coordinated ventricular contraction and decreases in mitral regurgitation by early an activation of the papillary muscle. The optimisation of the AV interval abolishes pre-systolic mitral regurgitation and prolongs the diastolic filling time. Relative optimisation of ventricular loading conditions as provided by CRT improves myocardial efficiency at no increased oxygen cost and increases the systolic function with little effect on the diastolic function. In addition to the positive hemodynamic effects mentioned above, CRT reduces sympathetic activity. With CRT, optimal responders develop smaller left ventricles and contractility is improved in the subsequent days or weeks (“reverse remodeling”)(1).
It is estimated that  about 10% of heart failure patients meet current guidelines for the use of CRT (1).

Technical details

Other than the conventional right ventricle and right atrial leads, CRT pacing requires the insertion of an extra lead into the coronary sinus. The lead is advanced into a tributary vein in order to achieve epicardial pacing from the postero-lateral LV wall. Several variations exist to this usual configuration. The CRT device has more sophisticated software and hardware than standard pacemakers and requires more extensive follow-up visits and, thus, a higher cost. These higher costs could be balanced, at least partly, by the reduction in hospitalisation and other therapies. Formal cost-effectiveness analysis have not yet been performed.
Since most of these patients are at high risk of life-threatening ventricular arrhythmias, CRT devices are usually combined with automatic defibrillation capabilities (CRT-ICD).

Indications

CRT is currently indicated for selected patients with symptomatic heart failure. These patients should be in a functional New York Heart Association class III, they should have a QRS duration of 130 ms or greater, left ventricular ejection fractions of 35% and left ventricular end-diastolic diameters >55 mm for one to see improvement in symptoms, functional status, and exercise capacity (2).
The efficacy of CRT for the treatment of patients with narrow QRS duration has only recently been explored as more definitive measures of detecting asynchrony by means of imaging techniques (3).
 There are other potential uses for CRT, and these should be evaluated in appropriate clinical trials in the future. Specifically, selected patients with atrial fibrillation and heart failure might
benefit from this form of therapy. Patients with heart failure with standard right ventricular pacemakers and ventricular a dyssynchrony that follows might also benefit from CRT (2).

Clinical results that can be reasonably expected

Evidence from several clinical trials suggests that CRT improves quality of life, reduces combined measures of morbidity and hospitalisation and probably reduces mortality especially when used with a defibrillator. The magnitude of the effects largely vary between patients. The situation is almost certainly one in which some patients are showing marked clinical benefit, balanced by other patients with very little benefit (2).

Pittfalls

Failure to achieve a long-lasting effective pacing from the coronary sinus for technical reasons still occurs in up to 15% of cases (4). Complications related to the procedure occur in up to 6% of cases (). 
Up to a quarter of patients who appear to be ideal candidates for CRT do not show the expected clinical and hemodynamic benefit. Whether this is the result of a less than optimal selection of pacing sites or other factors is presently unclear. Up to a quarter of LBBB patients do not show evidence of LV dyssynchrony at echocardiographic evaluation. If the predictive value of tissue-Doppler echocardiography or other imaging techniques are confirmed (5), these techniques could help provide a better stratification. Ensuring that dyssynchrony has been eliminated by careful selection of the ventricular locations for CRT therapy may reduce the number of non-responders to this form of therapy.

Unresolved issues

There are a number of issues that remain unresolved as regards CRT therapy. First, it is not clear whether dyssynchrony represents a cause or a consequence of heart failure. It seems possible that it may be a marker of progressive cardiac dysfunction. Secondly, there is a paucity of evidence as regards to potential long-term clinical benefit from CRT; clinical trials that have been done to date are relatively short, months to 1 year. Thirdly, the efficacy of CRT for the treatment of patients with narrow QRS duration has only recently been explored as more definitive measures of detecting asynchrony evolve. Can earlier application of CRT before ventricular dilatation alter the natural progression of dilated congestive cardiomyopathy? Can left ventricle-only pacing achieve long-term effects similar to those of biventricular stimulation? Lastly, CRT is expensive. Therefore, there is a need to be very mindful of these costs when recommending CRT for individual patients (2).

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

References


1. Auricchio A, Abraham WT. Cardiac resynchronization therapy: current state of the art: cost versus benefit. Circulation. 2004;109:300–307.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14744954

2. Willerson J, Kereiakes D. Cardiac resynchronisation therapy. Helpful now in selected patients with CHF. Circulation 2004; 109: 308-309.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14744955

3. Kass DA. Predicting cardiac resynchronization response by QRS duration: the long and short of it. J Am Coll Cardiol. 2003;43:2125–2127.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14680738

4. Abraham W, Fisher W, Smith A, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002; 346: 1845-1853.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12151867

5. Penicka M, Bartunek J, De Bruyne B, et al. Improvement of left ventricular function after cardiac resynchronization therapy is predicted by tissue doppler imaging echocardiography. Circulation 2004; 109; 978-983.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14769701

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.