**3. The dilemma of intelligent resynchronization therapy subjects selection**

The philosophy of resynchronizing the electrical stimulation of both ventricles developed into more mature practice, nowadays. The current CRT guidelines are the product of knowledge of the aforementioned clinical trials (**Table 1**) in addition to the accumulation of personal and institutional expert opinions. The most important organizations contributing most importantly to today's guidelines are: American Heart Association, the American College of Cardiology, Heart Rhythm Society, the Heart Failure Society of America, and the European Society of Cardiology. American criteria to define LBBB as defined by AHA/ACC/HRS are as follows:


The vast majority of recommendations of those organizations are concordant to each other making class I indications clear for CRT specialists to implement. Class I indications are restricted to the symptomatic patients with LVEF ≤35%, NYHA II-IV, with a QRS duration ≥130 ms despite guideline-directed medical treatment (GDMT) [15]. The most recent guidelines are account for the observations that the greatest benefits are consistently seen in those with a QRS duration >150 ms and LBBB pattern [16–18]. On the other hand, echocardiographic evaluation looking for mechanical dyssynchrony results of the Predictors of Response to CRT (PROSPECT) Trial published in 2008 did not show superiority for CRT outcome for any of the predictors [19]. Accumulation of data in the last two decades demonstrated clearly that the CRT success in electrical resynchrony, mechanical remodeling, and quality of life improvement is not always directly linked to the current selection criteria. Response to CRT seems to be more complex than we thought earlier. Currently, 30–40% of our subjects are non-responders. We recommend extension criteria for CRT subjects selection considering the old criteria of QRS duration >130 ms, LV dysfunction (<35%), and NYHA class II-IV as a guideline with more extensive clinical, pathological, imaging and programming variables to be considered. Critical variables such as global scar burden, scar location, lead position, programmed AV and VV interval, mitral regurgitation, and irreversibly advanced heart failure cases are imperative considerations to improve the outcome [20] Despite the traditional dogma that normal QRS duration is a contraindication for CRT, recent challenging groups suggest that QRS complex <130 ms might benefit from CRT. This response as they describe it, is personalized but having QRS complex <130 ms should not be a reason to withhold the option of CRT in systolic heart failure if no other effective treatment is available [21]. Despite the claim that CRT is under-utilized worldwide, we suggest more wise selections

*CRT Past, Present, and Future Directions: Toward Intelligent Responders Selection… DOI: http://dx.doi.org/10.5772/intechopen.101608*

with the advanced criteria for more intelligent selection. Our top priority should be the perfection of patients' choices to optimize benefits from CRT. Adjunction of defibrillator therapy with CRT as primary prevention of SCD is indicated in most CRT patients. For this reason, current guidelines advocate an implant of a CRT-D in eligible patients [9, 12]. Most of the systems we are implanting nowadays are CRT-D. This addition of defibrillator stress more for the need of more intelligent and comprehensive criteria for subjects selection. It is imperative to treat any primary disease before thinking of introducing the choice of CRT. Reversible heart diseases such as myocardial ischemia, arrhythmia (tachycardia-induced cardiomyopathy), or primary valvular heart disease must be treated. When AF is a risk factor, catheter ablation of AF is superior to AV node ablation combined with biventricular pacing. This superiority is increasing with the dramatic improvement in our skills and technology, especially with pulmonary veins cryoablation technique. In the subgroup of patients who received prior pacemaker or ICD with worsening heart functions, an upgrade plan for CRT-D seems appropriate. The majority of patients we are implanting, died without experiencing an appropriate ICD shock. A selection system that is capable of predicting survival in patients who received a CRT-D as primary prevention of SCD, identify a subgroup with a significantly poor prognosis despite a CRT-D, as well as being able to discriminate between patients with a low or high risk for mortality, is highly needed. The predictive HF meta-score is constructed of independent mortality predictors identified in a meta-analysis. Three continuous variables constitute this comprehensive evaluation score. In addition to age, LVEF and eGFR, New York Heart Association (NYHA) functional class; 11 dichotomous variables which give the score true discriminative strength including: male gender, African-American race, diabetes, chronic obstructive pulmonary disease, peripheral vascular disease, ischemic cardiomyopathy, HF admission within 1 year before implantation, past or present atrial fibrillation, wide QRS (≥120 ms), secondary prevention indication, and history of ICD shocks (appropriate and inappropriate) [22]. The authors of this meta-analysis found the HF meta-score, a good predictor for survival and useful to detect a subgroup with a significantly poor prognosis despite a CRT-D. In addition, accumulated medical literature in the last few years pin point other conduction system disorders in addition to the major well-known indication of the LBBB as potential indications for CRT. Those indications were based on evidence derived from sub-analyses from the landmark trials and will be discussed in the next section.
