**9. Conclusion**

CHF is one of the most important epidemics in the current human species era affecting 1–2% of adults and around 10% of >70 years old in developed countries. In addition to its psychophysiological and social burden, the economic impact of CHF on the world nations is Gargantum. Treatment options for CHF witnessed relative stagnation until 2001, where the first electrical device in the form of biventricular pacing to resynchronize the failing desynchronized ventricles, was implanted in 2001. In spite of the early excitement for this type of therapy most international landmark trials reported 30–40% of non-responders. Factors contributing to this large proportion of non-responders are related to scar burden and scar localization to the vicinity of the LV pacing stimulus, hypocontractility, and the degree of pre-implant mechanical dyssynchrony. It was surprising to medical communities to discover that a significant proportion of CHF without LBBB responds to CRT. This chapter is a scientific journey to understand the pathophysiological mechanism to optimize the selection of CRT responders. We confirm that LBBB is deficient criteria for selecting CHF patients for CRT. A spectrum of ventricular

conduction disorders that might benefit from CRT, as derived from landmark trials were discussed including IVCD and RBBB. New techniques to detect dominant left ward electrical delay (LED) including endocardial 3-dimensional electroanatomical mapping and ECG imaging or body surface mapping to display electrical activation sequences as well as the elaboration of the best electrical substrate to optimize response to CRT in IVCD, RBBB, and atrioventricular delay are discussed. Determination of pre-implant degree of dyssynchrony is critical as pacing is known to induce more dyssynchrony for mild cases at the baseline with clinical and hemodynamic compromise. For this reason, special attention in this chapter was devoted to new echocardiographic mechanical dyssynchrony markers like eyeballing, septal flash, and time-based mechanical dyssynchrony markers. Systolic septal rebound stretch (SRSsept) was found to be an excellent echocardiographic discriminator to predict response to CRT. Cardiovascular Magnetic Resonance (CMR) was found to be an ideal radiation-free diagnostic tool for the diagnosis of the actual heart failure substrate and accordingly to optimize CRT responders selection. CRM is known to be the gold standard for scar diagnosis but is also considered to be an excellent diagnostic tool for fibrosis, myocarditis, sarcoidosis, arrhythmogenic right ventricular cardiomyopathy, amyloidosis, and Anderson-Fabry disease. Computed tomography is also an excellent tool to diagnose myocardial scar as well as for coronary venous system reconstruction images for optimal LV lead positioning. An innovative future direction for the best outcome of CRT is discussed. The non-invasive nature of vectorcardiography (VCG) with its strong prediction capabilities for volumetric as well as survival indicators after CRT, makes VCG an attractive adjunct diagnostic tool to optimize CRT responders selection. Improving our understanding of the biomechanics of cardiac electromechanical coupling and the contribution of the spatial orientation of the ventricular muscle band to cardiac pumping functions is creating a new visionary approach toward understanding the extent of LV mechanical dysfunction and perfective lead positioning in CRT subjects. New LV lead positions like pacing the LV endocardium reflect a more rapid and physiological activation of the left ventricle with excellent early results. Permanent pacing of the His bundle region to achieve ventricular resynchronizing has been described, with clear clinical advantages over biventricular pacing. Progressive narrowing in QRS duration was documented with HB pacing compared to conventional CRT with the best narrowing was gained with His-optimized cardiac resynchronization therapy (HOT-CRT). This multi-disciplinary approach to optimize CRT response is promising for a better future of resynchronization therapy aiming toward the best possible quality of life for this important group of CHF subjects in the next decades.
