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Friday, February 28, 2020

What do Left bundle banch block and traditional right ventricular cardiac pacing have in common?

Although it was demonstrated at least as early as 1989 by CL Grines et al (1) that left bundle branch block (LBBB) could cause significant functional impairment of the left ventricule (LV), clinical description and  general recognition of a LBBB cardiomyopathy as a clinical entity would require a decade or more.

Pacing the apex of the right ventricule was the default method for cardiac pacemaker implantation for many years and  the path to recognition of a right venricular pacing induced cardiomyopathy and a better way to pace was neither short nor particularly straight.

In 2005 (Blanc et al ) and in 2013 (Vaillant) reports appears describing a dilated cardiomyopathy apparently induced by LBBB that in some instances were significantly reversed by cardiac resynchronization treatment (CRT).Blanc wrote "long standing LBBB may be a newly identified reversible cause of cardiomyopathy."

Further proof was offered by Barot et al (2017) in the form of a  retrospective followup report.Thirteen of 94 LBBB patients with normal cardiac function (normal ejection fraction (EF) and no evidence of coronary artery disease developed a significant reduction in LV function over a variable time.

Not only is LBBB dyssynchronopathy heart failure now recognized it has become apparent that the usual heart failure meds do not seem very effective. In 2015, NC Wang et al reported the lack of response  to medical therapy in 32 LBBB patients with new onset LBBB-associated idiopathic non-ischemic cardiomyopathy (NICM) and that "a high percentage were super-responders [to CRT]."

James Daubert and Edward Sze (3)argued in 2018 that the then current guidelines for implanting CRT require at least 3 months of guide-line directed therapy (GDMT) before implantation but there are no randomized clinical trials showing efficacy of medications and suggested that CRT should be  considered for first line therapy rather than GDMT as many  (most) symptomatic patients with LBBB do not respond to GDMT.

Since the early 1990s CRT has become an important treatment for heart failure  with reduced ejection fraction (HFrEF) and delayed intra-ventricular conduction with the greatest benefit in those patients with LBBB.CRT traditionally has meant right ventricular pacing plus pacing the left ventricle from a vein on the surface of the left ventricle accessed through the coronary sinus.This is referred to as Bi-V.  or biventricular pacing.More recently His Bundle pacing (HBP) has been suggested as being as good  and perhaps better than Bi-V or at least as an alternative in cases in which the coronary sinus lead could not be placed.In cases in which the mechanical dyssynchrony is caused by an electrical problem an electrical "fix" seems necessary.HBP would seem to be the best fix being more physiological than Bi_V pacing .

Placing a pacing lead in the apex of the right ventricle was standard procedure for bradycardia indications for many years before EP cardiologists raised the question and then gathered evidence and finally  concluded that in fact RV pacing could lead to significant loss of synchrony in the LV which   resulted in heart failure in a significant number of patients

The similarities of the EKG in right apical pacing and LBBB certainly suggested possible functional impairment from RV pacing.Cardiologists were interested in some alterenative pacing method to avoid the harm that was becoming evident in RV pacing but no good alternative presented itself, at least not until HBP.Reports of septal pacing in place of apical pacing gave conflicting results.

As effective as traditional CRT (i.e. Bi-v) is some 30 % plus of patients with HF do not response while some seem to be "super-responders".Patients with narrow QRS complexes do not respond and those with a LBBB pattern are more likely to respond but all patients with a similar LBBB EKG pattern do not all respond to the same degree nor do they necessarily have the identical patern of LV electrical activation.All patients with an EKG designation of LBBB are not created equal.

The typical pattern of LV contraction described in LBBB is the following:

The interventricular septum moves quickly to the left in early systole (in the isovolumic contraction phase, i.e before aortic valve opens).The LV lateral wall is pushed  outward and finally the electrical impulse traveling through myocytes reaches the lateral left wall area and it contracts pushing  the septum to the right.

The initial left shift of the septum is mainly  the result of the electrical impulse traveling from right to left (the opposite of the normal situation) and also from the pressure difference between the RV and LV as the RV contracts before the delayed LV contraction. This initial septal shift is called septal flash or septal beak and can be seen on M mode echo as well as on speckletracking echo.

Calle et al (2 ) have proposed that this septal flash may be the key to what "true LBBB" is- meaning the pattern of dyssynchrony that is responsible for the functional impairment and the pattern most "fixable" by CRT and by HBP as regards both LBBB and right apical pacing induced dysfunction.

Various other echo criteria have been proposed as the preferred measure to assess dyssynchrony and response to CRT without general agreement. About 50% of patients with the EKG pattern of LBBB are shown to have the septal flash and the associated dysfunctional out-of-sync LV contraction.

The septal flash indicates that the septum is activated from right to left initiating a sequence of dyssynchronous ventricular segmental contractions and relaxations that are deleterious to ventricular function and may result in remodeling and ultimately heart failure with reduced ejection fraction and is often reversible to varying degrees with CRT either by HBP or Bi-V.

So would CRT be expected to be useful in patients with RBBB since the septal  activation is from left to right.In theory- no but Sharma ( 3) et al have reported significant clinical improvement
 in some RBBB heart failure patients treated with HBP.Perhaps right to left septal activation ( as indicated by septal flash) is not a necessary condition for there to be improvement from CRT but I doubt one would see a super-response and the mechanism of benefit may relate more to improved atrial-ventricular synchrony improvement  and not correction of an abnormal septal activation.

1) Grines, Cl et al Functional abnormalities in isolated left bundle branch block.The effect of interventricular asynchrony. Circulation  1989 79 845-853

2)Calle,D et al, Septal Flash :At the heart of cardiac dyssynchrony. Trends in Cardiovacsular Medicine2019,14,9

3)Sze,E and Daubert,JP Left bundle blck induced left ventricular remodeling and its potential of reverse remodeling. J Intv Card Electrophysiol 52 (3) 343-352, 2018