Update on Indications for Cardiac Resynchronization Therapy

Maria Rosa Costanzo, M.D., F.A.C.C., F.A.H.A.Medical Director, Midwest Heart Specialists-Advocate Medical Group

Heart Failure and Pulmonary Arterial Hypertension ProgramsMedical Director, Edward Hospital Center for Advanced Heart Failure

Naperville, Illinois, U.S.A.

ACC/AHA DBT guidelines, 2012

2012 ACCF/AHA/HRS Focused Update of the 2008 Guidelines for

Device-Based Therapy of Cardiac Rhythm Abnormalities

Class I CRT is indicated for pts. who have LVEF ≤ 35%, SR, LBBB with

a QRS duration ≥ 150 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT.

Level of Evidence: A for NYHA class III/IV (MIRACLE, COMPANION, CARE-HF);

Level of Evidence: B for NYHA class II (MADIT-CRT)

Comments Modified recommendation

specifying CRT in pts with LBBB of ≥150 ms expanded to include those with NYHA class II symptoms

Tracy CM et al. JACC 2012:60:1297-1311

2012 ACCF/AHA/HRS Focused Update of the 2008 Guidelines for

Device-Based Therapy of Cardiac Rhythm AbnormalitiesClass IIa

CRT can be useful for pts. with LVEF ≤ 35%, Sr, LBBB with a QRS duration 120 to 149 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT. (Level of Evidence: B)

CRT can be useful for pts who have LVEF ≤ 35%, SR, a non-LBBB pattern with a QRS duration ≥ 150 ms, and NYHA class III/ambulatory class IV symptoms on GDMT. (Level of Evidence: A)

CRT can be useful in pts. with AF and LVEF ≤ 35% on GDMT (Level of Evidence: B) if

a) the patient requires ventricular pacing or otherwise meets CRT criteria and b) AV nodal ablation or pharmacologic rate control will allow near 100% ventricular pacing with CRT.

CRT can be useful for pts. on GDMT who have LVEF ≤ 35% and are undergoing new or replacement device placement with anticipated requirement for significant (>40%) ventricular pacing). (Level of Evidence: C)

Comments New recommendation

New recommendation

Modified recommendation (wording changed to indicate benefit based on EF rather than NYHA class; level of evidence changed from C to B).

Modified recommendation (wording changed to indicate benefit based on EF and need for pacing rather than NYHA class); class changed from IIb to IIa).

2012 ACCF/AHA/HRS Focused Update of the 2008 Guidelines for

Device-Based Therapy of Cardiac Rhythm Abnormalities

Class IIb

CRT may be considered for pts. who have LVEF ≤ 30%, ischemic HF etiology SR, LBBB with a QRS duration ≥ 150 ms, and NYHA class I symptoms on GDMT. (Level of Evidence: C)

CRT may be considered for pts. who have LVEF ≤ 35%, SR, a non-LBBB pattern with QRS duration 120 to 149 ms, and NYHA class III/ambulatory class IV on GDMT). (Level of Evidence: B)

CRT may be considered for pts. who have LVEF ≤ 35%, SR, a non-LBBB pattern with a QRS duration ≥ 150 ms, and NYHA class II symptoms on GDMT. (Level of Evidence: B)

Comments

New recommendation

New recommendation

New recommendations

Tracy CM et al. JACC 2012:60:1297-1311

2012 ACCF/AHA/HRS Focused Update of the 2008 Guidelines for

Device-Based Therapy of Cardiac Rhythm Abnormalities

Class III

CRT is not recommended for pts. with NYHA class I or II symptoms and non-LBBB pattern with QRS duration < 150 ms. (Level of Evidence: B)

CRT is not indicated for pts whose comorbidities and/or frailty limit survival with good functional capacity to less than 1 year ). (Level of Evidence: C)

Comments

New recommendation

Modified recommendation (wording changed to include cardiac as well as noncardiac comorbidities).

Tracy CM et al. JACC 2012:60:1297-1311

The Influence of Left Ventricular Ejection Fraction on the Effectiveness of Cardiac Resynchronization Therapy: MADIT-CRT

Kutyifa V et al. JACC. 2013;61:936-944

The Influence of Left Ventricular Ejection Fraction on the Effectiveness of Cardiac Resynchronization Therapy: MADIT-CRT

Kutyifa V et al. JACC. 2013;61:936-944

The Influence of Left Ventricular Ejection Fraction on the Effectiveness of Cardiac Resynchronization Therapy: MADIT-CRT

Kutyifa V et al. JACC. 2013;61:936-944

Device Therapy in Heart Failure: Has CRT Changed “the Sickest Benefit the Most”

to “the Healthiest Benefit the Most?”

JACC 2013;61(9):945-947

Differential Response to CRT by QRS Morphology and Duration

Dupont M et al. JACC 2012; 60: 592-8

Histogram of QRS Duration in the Study Population

Dupont M et al. JACC 2012; 60: 592-8

Echocardiographic and Clinical Response to CRT by QRS Morphology and Duration

After CRT, patients with LBBB morphology and/or QRS duration ≥ 150 ms had statistically significantly greater improvement in: EF LVEDD LVESD MR grade change % of super-responders NYHA functional class

Dupont M et al. JACC 2012; 60: 592-8

Survival after CRT Implantation

Dupont M et al. JACC 2012; 60: 592-8

Cox Proportional Hazards Models for Death, Heart transplantation and LAVD PlacementVariable Adjusted HR P ValueLBBB and QRS ≥ 150 ms

1.00

LBBB and QRS <150 ms

1.52 (0.95-2.38) 0.08

Non-LBBB and QRS ≥ 150 ms

1.01 (0.65-1.55) 0.96

Non-LBBB and QRS <150 ms

1.42 (0.93-2.15) 0.10

Male 2.17 (1.14-3.44) 0.0003Age > 70 0.84 (0.60-1.17) 0.30Ischemic CM 1.55 (1.09-2.24) 0.01eGFR 0.98 (0.98-0,99) < 0.0001Baseline EF 0.97 (0.95-0.99) 0.01

Dupont M et al. JACC 2012; 60: 592-8

Hsu JC et al. J Am Coll Cardiol. 2012; 59(25):2366-2373

Changes in Echocardiographic Parameters in Super-Responder, Responder and Hyporesponder Groups

Multivariable Analysis of Predictors of LVEF Super-Response

Variable Odd Ratio 95% CI P valueFemale 1.96 1.32-2.90 0.001

QRS ≥ 150 ms 1.79 1.17-2.73 0.007

LBBB 2.05 1.24-3.40 0.006

BMI < 30 Kg/m2 1.51 1.03-2.20 0.035

No Prior MI 1,80 1.20-2.71 0.005

LAVI 1.47 1.21-1.79 < 0.001

Hsu JC et al. J Am Coll Cardiol. 2012; 59(25):2366-2373

Kaplan-Meier Estimates of Cumulative Probability of Heart Failure or Death, Death Alone, and Death or ICD Therapy for VT or VF Stratified by Response Category

Hsu JC et al. J Am Coll Cardiol. 2012; 59(25):2366-2373

Cox Proportional Regression Analysis of Predictors

of Nonfatal HF Events or DeathVariable Hazard Ratio 95% CI P valueLVEF response Super-responder Reference

Hypo-responder 5.25 2.01-13.74 0.001

Responder 2.24 0.86-5.83 0.099

LBBB 0.57 0.34-0.94 0.029

Creatinine ≥ 1.4 mg/dL 3.02 1.66-5.49 < 0.001

Hsu JC et al. J Am Coll Cardiol. 2012; 59(25):2366-2373

ACC/AHA DBT guidelines, 2012

ConclusionsSince the publications of the Miracle trial the indications for CRT have evolvedMeasures of mechanical dyssinchrony have been largely disappointing in predicting response to CRTQRS duration has endured as the single stronger predictor of CRT responseThe MADIT-CRT trial has extended the indications for CRT to patients with prolonged QRS and mild HF symptomsThe ability to predict non-responders to CRT remains elusiveThe ADVANCED-CRT Registry will help to characterize non-responders to CRT and to refine selection criteria for CRT