In this article, we reviewed the major trials that enriched the most recent international guidelines for CRT implantation focusing on the available data about the outcome of using CRT in non-LBBB cohort. It remains uncertain whether patients with non-LBBB QRS complex morphology clearly benefit from CRT or only modestly respond. An important and consistent finding in published systematic reviews and in subgroup analyses is that the benefits of CRTs are maximum for patients with a broader QRS durations, typically described as QRS duration > 150 ms, and for patients with a typical left bundle branch block (LBBB) QRS morphology. The QRS area and T area and some of the QRS and T area have been shown to be strong predictors of volumetric response and survival after CRT, but they are not commercially available for clinical practice.Cardiac resynchronization therapy (CRT) benefits have been firmly established in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), who remain in New York Heart Association (NYHA) functional classes II and III despite optimal medical therapy, and have a wide QRS complex. The area under the three-dimensional QRS complex and three-dimensional T-wave reflect unopposed electrical forces during ventricular depolarization and repolarization, respectively.
Vectorcardiography is a method for recording three-dimensional information about the direction of the electrical forces. Time to peak dyssynchrony measures on echo are not specific to the electrical substrate responsive to CRT, and therefore, they are unlikely to be effective for selecting patients that may benefit from CRT. Strain-based speckle tracking echocardiography–derived dyssynchrony (systolic stretch index) and the visual assessment of dyssynchrony (septal flash and apical rocking) are potential emerging echocardiographic parameters for CRT consideration. The existence of atrioventricular dyssynchrony, represented by prolongation of the PR interval on the electrocardiogram, is also a potential target for CRT. Typical RBBB shows wide S-wave in the lateral lead 1 and aVL, while atypical RBBB pattern lacks S-wave in lead 1 and aVL, and coexisting left-axis deviation, and may be associated with coexisting PR prolongation due to delayed activation over the left bundle. An atypical RBBB may identify possible CRT responders. Published data from the National Cardiovascular Data Registry’s ICD Registry showed that CRT was associated with better outcomes than implantable cardioverter-defibrillator (ICD) therapy alone in IVCD patients with a QRS duration ≥150 ms, but not in patients with QRS duration <150 ms or RBBB of any duration. Despite some positive results from such studies, widespread clinical application of detailed electrical mapping is limited given its time consumption and invasive nature. Intracardiac mapping studies show that 20-50% of patients who have an IVCD may have significant delay of activation in the left lateral ventricle. Some patients without a typical LBBB may exhibit an electrical activation that is very similar to that seen in patients with typical LBBB (e.g., patients with LBBB and subsequent anterior myocardial infarction). 
There are three main criteria for the diagnosis of LBBB-American Heart Association/American College of Cardiology/Heart Rhythm Society criteria, the European Society of Cardiology, and the Strauss criteria-and there is a significant interobserver and intraobserver variability in the classification of the LBBB by the use of the various definitions. Multicenter randomized studies LESSER-EARTH and ECHO-CRT included patients with QRS complex duration <120 ms and <130 ms, respectively, and were both terminated early due to lack of efficacy, worsened outcomes, and even increased mortality (in the case of ECHO-CRT). Biventricular pacing in patients unlikely to benefit from CRT is not benign ipso facto it induces dyssynchronous electrical activation. A significant degree of dyssynchrony is required for benefit from CRT. 
Prospective randomized trials of CRT in patients with RBBB or IVCD are lacking.
CRT is well established in patients with typical LBBB, and controversial in patients with electrical delay and no LBBB-right bundle branch block (RBBB) and intraventricular conduction delay (IVCD).
The following are key points to remember from this state-of-the-art review about cardiac resynchronization therapy (CRT) in patients with heart failure and without typical left bundle branch block (LBBB):
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