CLASS I CRT is indicated for

1- EF< 35%, NSR, LBBB with QRS > 150, NYHA Classes II, III, or IV                                                                   (B)

CLASS IIa CRT can be useful for

1- EF < 35%, NSR, LBBB with QRS 120-149, NYHA Classes II, III, or IV                                                              (B)
2- EF < 35%, NSR, non-LBBB with QRS > 150, NYHA Classes III or IV                                                                (A)
3- EF < 35%, AF if      the patient requires V pacing or meets CRT criteria
                 and      AVN ablation or pharmacological control will allow near 100% V pacing with CRT     (B)
4- EF < 35%, undergoing generator replacement or new implant, anticipated RV pacing > 40%                  (C)

CLASS IIb CRT may be considered in

1- EF< 30%, ICM, NSR, LBBB with QRS > 150, NYHA Class I                                                                              (C, new)
2- EF < 35%, NSR, non-LBBB with QRS 120-149, NYHA Classes III or IV                                                          (B, new)
3- EF < 35%, NSR, non-LBBB with QRS > 150, NYHA Class II                                                                             (B, new)

CLASS III CRT is contraindicated in

1- Regardless of EF, NYHA Classes I or II with non-LBBB and QRS < 150                                                      (B, new)
2- Survival < 1 year                                                                                                                                                (C, modified)

Progression of LV systolic dysfunction => clinical heart failure is frequently accompanied by impaired electro-mechanical coupling
Prolonged AVD
Prolonged IV conduction (most commonly LBBB) - observed in 1/3 of patients with advanced heart failure
Regional mechanical delay within the LV
Altered myocardial metabolism
Functional MR
Adverse remodeling with ventricular dilatation

CRT can improve ventricular systolic function, reduce metabolic costs, ameliorate functional MR, and, in some patients, induce favorable
remodeling with reduction of cardiac chamber dimensions.
Functional improvement has been demonstrated for exercise capacity, with improvement in peak oxygen consumption of 1-2 mL/Kg/min,
and a 50-70 meter increase in 6-minute walking distance, as well as a > 10 point reduction of HF symptoms on the 105-point Minnesota
Living with Heart Failure scale.

-Meta-analysis of initial clinical experience: 30% decrease in hospitalizations and 24-36% decrease in mortality.
-COMPANION trial (EF < 35%, QRS >120, Class III/IV): 20% reduction in primary endpoint (HF, hospitalizations), and 36% reduction
in mortality compared to medications alone. But there was insufficient evidence to conclude that CRT-PPM was inferior to CRT-D.
-CARE-HF trial (QRS> 150 (89%) or QRS 120-150 with echo evidence of dyssynchrony (11%)): was the first trial to demonstrate a
36% reduction in death rate in CRT-PPM group alone without defibrillator therapy, compared to medical therapy.

The prevalence of mechanical dyssynchrony has been documented in > 40% of patients with DCM and QRS > 120, and as high
as 70% of patients with DCM and QRS > 150 and dyssynchrony identified by echo.

-META-ANALYSIS of 5 trials involving 6501 patients: QRS > 150
CRT decreased the primary endpoint of death or hospitalization for HF in patients with QRS > 150 (HR 0.58, CI 0.50-0.68, p<0.00001), but
not in patients with QRS < 150 (HR 0.95, CI 0.83-1.10, p=0.51). This observed differential benefit of CRT was observed in all classes NYHA
I through IV.
It is from this met-analysis that patients with QRS < 150 are afforded Class II Indications.
Stavrakis S, Lazzara R, Thadani U. The benefit of cardiac resynchronization therapy and QRS duration: a meta-analysis. J Cardiovasc Electrophysiol. 2012;23:163– 8.

                  Class I Indication is limited to patients with LBBB and with QRS > 150

-META-ANALYSIS of 4 trials involving 5356 patients: LBBB
In patients with LBBB, CRT significantly reduced adverse clinical events (RR: 0.64, CI 0.52-0.77, p=0.00001)
No benefit was observed for patients with non-LBBB conduction abnormalities (RR 0.97, CI 0.82-1.15, p=0.75)
RBBB (RR 0.91, 95%B CI 0.69-1.20, p=0.49)
IVCD (RR 1.19, 95% CI 0.87-1.63, p=0.28)

-RAFT (EF<30%, QRS > 120, NYHA II-III ICM or NICM, CR vs ICD). Primary outcome of death or hospitalization for HF occurred in 33%
of patients receiving CRT-D and in 40% receiving ICD alone. RAFT did not only show a significant reduction in hospitalizations but also was
the first study to show a significant reduction in death in mildly symptomatic NYHA Class II patients. CRT-D was associated with a higher risk
of adverse device or implantation related complications at 30 days from implantation. RAFT showed CRT to be more effective in patients
with LBBB conduction abnormality and with prolonged QRS > 150.

-Wider RV-LV lead placement

The most significant changes in the present document compared to the 2008 DBT Guidelines are the expansion of the Class I
recommendation for CRT to include patients with LBBB, QRS duration >150 ms, and NYHA  class II and the addition of a Class IIb
recommendation for patients who have LVEF <30%, ischemic etiology of HF, sinus rhythm, LBBB with a QRS duration of >150 ms,
and NYHA class I symptoms (based on 4 studies: MADIT-CRT, RAFT, REVERSE, MIRACLE ICD II)

-MADIT CRT (EF< 30%, ICM, LBBB with QRS > 130, NYHA I (only 15%)-II ICM and NYHA II NICM, CRT vs ICD). Primary endpoint
of death or HF event was reduced by
34% by CRT with comparable benefit from ICM and NICM. HF events were reduced by 41% without
significant reduction in mortality. CRT-D therapy demonstrated to be of more benefit in women > men and in patients with QRS > 150.
Patients with LBBB had a significant reduction in VT, VF and death.

-REVERSE (EF < 40%, QRS > 120,  610 patients with NYHA Class I-II followed for 12 months). REVERSE showed that 16% of
patients receiving CRT and 21% without CRT worsened.
 The time for first HF hospitalization was delayed with CRT therapy. REVERSE did
not report a mortality rate benefit of CRT-D.
This could be related to the higher EF enrollment criterion and the relatively short term
follow up.

-MIRACLE ICD II (EF < 35%, QRS > 130, NYHA Class II)