Cardiac Resynchronization Therapy Jeffrey J. Shultz, MD Cardiac Electrophysiology Park Nicollet Heart and Vascular Center

Case: DK – 69 y/o male 2006 - Aortic valve replacement and CABG. (No h/o MI) LVEF remained approximately 45% LBBB (ECG to be shown) NYHA Class I Carvedilol 25 mg BID, Lisinopril 20 mg daily, HCTZ, Coumadin, ASA, Amlodipine, Lipitor 2014 – Episodic dyspnea, LVEF down to 35% Lasix and spironolactone added Jan 2015 - Progressive DOE, NYHA Class III, Stress test = inferior ischemia and LVEF=20% Feb 2015 – Cor Angio = non- occlusive CAD. Rx = Med Mgmt. June 2015 – Remains NYHA Class III, LVEF=30%, Referred for Bi-V ICD

DK – 69 y/o male

Congestive Heart Failure - Magnitude of the Problem Estimated 5.1 million in US / 23 million worldwide (2006) Exact numbers difficult due to varying inclusion criteria Steep rise in incidence with age 3-4-fold increase in hospitalizations from 1971-1999 Increase in Mortality attributable to CHF from 5.8/1000 in 1970 to 16.4/1000 in 1993 $32 billion spent on treatment of CHF in US / year

DeatHs due to coronary heart disease NHLBI 2012

Hospitalizations due to CHF NHLBI 2012

Age-related CHF Incidence (#/1000) le Male Age-related CHF Incidence (#/1000) Female Bleumink, et.al. EHJ 2004

1. Framingham Heart Study (1948 – 1988) in Atlas of Heart Diseases. 2. American Heart Association. Heart Disease and Stroke Statistics—2003 Update.

Systolic versus Diastolic CHF Systolic – HF-REF Diastolic – HF-PEF Impaired contractility / ejection LVEF <50% Approximately 2/3 of CHF prevalence Common conditions - Ischemic CM, DCM Multiple approaches to therapy Impaired LV relaxation / filling LVEF = >50% Approximately 1/3 CHF prevalence Common conditions – HTN, elderly without HF-PEF, HCM, constrictive/ restrictive CM Limited therapeutic options

HF-pef vs hf-ref mortality Brouwers et.al, EHJ 2013

1. The Criteria Committee of the New York Heart Association 1. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & Co; 1994:253-256

Weapons against Systolic CHF Prevention – Education and management of CAD risk factors Aggressive treatment of UA/STEMI/Non-STEMI Medical therapy – ACE-I’s/ARB’s, ß-blockers, aldosterone antagonists, diuretics Dietary / Fluid restrictions Aggressive outpatient monitoring programs Cardiac Resynchronization Therapy (CRT)

What is Dyssynchony? 3 types of dyssynchrony AV – Delay between atrial and ventricular contraction (AV block) Interventricular – Delay between right and left ventricular activation (LBBB) Intraventricular - normal ventricular activation sequence is disrupted, resulting in discoordinated contraction of the LV segments CRT can help with all three

Left Bundle Branch Block HOW DO WE MEASURE DYSSYNCHRONY? Left Bundle Branch Block - Currently best measure of left ventricular dyssynchrony - QRS duration > 120; preferably > 150 for CRT

CRT Devices CRT-D – Implantable Defibrillator capable of Bi-Ventricular Pacing (Most common) CDT-P – Pacemaker capable of Bi-Ventricular Pacing (Has no ability to treat ventricular tachyarrhythmias)

Coronary venous anatomy

Pressure Products® CSG® Worley Sheath

Coronary venous anatomy

LV lead placement Dong et.al; Europace 2012

CRT Indications - 2012 Class 1 -  LVEF less than or equal to 35%, sinus rhythm, LBBB with a QRS duration greater than or equal to 150 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT. Class 2a – LVEF less than or equal to 35%, sinus rhythm, LBBB with a QRS duration 120 to 149 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT. LVEF less than or equal to 35%, sinus rhythm, a non-LBBB pattern with a QRS duration greater than or equal to 150 ms, and NYHA class III/ambulatory class IV symptoms on GDMT. Atrial fibrillation and LVEF less than or equal to 35% on GDMT 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 Patients on GDMT who have LVEF less than or equal to 35% and are undergoing new or replacement device placement with anticipated requirement for significant (>40%) ventricular pacing.

CRT Indications - 2012 Class 2b Class 3 LVEF less than or equal to 30%, ischemic etiology of heart failure, sinus rhythm, LBBB with a QRS duration of greater than or equal to 150 ms, and NYHA class I symptoms on GDMT LVEF less than or equal to 35%, sinus rhythm, a non-LBBB pattern with QRS duration 120 to 149 ms, and NYHA class III/ambulatory class IV on GDMT LVEF less than or equal to 35%, sinus rhythm, a non-LBBB pattern with a QRS duration greater than or equal to 150 ms, and NYHA class II symptoms on GDMT Class 3 NYHA class I or II symptoms and non-LBBB pattern with QRS duration less than 150 ms Comorbidities and/or frailty limit survival with good functional capacity to less than 1 year.

REVERSE and RAFT (2012) REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) and RAFT (Resynchronization/Defibrillation in Ambulatory Heart Failure) trials showed that Cardiac Resynchronization Therapy (CRT-D) reduced Heart Failure (HF) Hospitalization or All-Cause Death. Looked at patients with; NYHA Class II Left Bundle Branch Block Left Ventricular Ejection Fraction ≤ 30% QRS duration ≥ 130 ms

REVerse and raft - results • REVERSE: Reduction of Worsened Clinical Composite Response from 18% with CRT OFF versus 5% with CRT ON (p = 0.004) (Figure 1) • REVERSE: 73% reduction in Time to First HF Hospitalization or All- Cause Death with CRT (p = 0.004) (Figure 2) • RAFT: 42% reduction in Time to First HF Hospitalization or All- Cause Death with CRT-D (p < 0.0001)

Reverse - results

Expanded CRT indications with reverse and raft NYHA III/IV** NYHA II QRS Duration Prolonged LBBB***, QRS ≥ 130 ms LVEF ≤ 35% ≤ 30% Optimal Medical Therapy Yes Approved Device(s) CRT-P, CRT-D CRT-D only In this slide, the one column shows the FDA-approved labeling that Medtronic (and other manufacturers) received for NYHA Functional Class III and Ambulatory Class IV patients. In comparison, the FDA-approved labeling for Medtronic CRT-D devices in the NYHA Class II patients requires a left bundle branch block, a QRS duration of greater than or equal to 130 ms, an ejection fraction of less than or equal to 30%, and optimal medical therapy. Note that the labeling is only for CRT-D and not CRT-P.

Block HF trial 2013 Objective: To determine if biventricular pacing with CRT is superior to right ventricular only pacing in patients with; Class I or IIa pacing indication NYHA class I, II, or III LVEF </=50% At least one of the following; 2nd or 3rd degree AV block 1st degree AV block with pacemaker syndrome Documented Wenchebach block or PR interval >300 msec with pacing at 100 BPM

Block hf - results

Updated recommendations - April 2014 AV block (prolonged 1st degree, 2nd or 3rd degree) NYHA Class I, II, III heart failure LVEF ≤ 50% Optimal medical therapy (OMT) 

DK – 68 y/o male Under went implant of CRT-D on 6/17/15 ECG to be shown Saw PMD on 7/21/15 – Feel great! No dyspnea or DOE. Seen in Cardiology 9/2/15 – NYHA Class I-II Echo – LVEF = 30% but LV chamber size noted to be smaller

DK – 69 y/o male

DK – 68 y/o male – post CRT-D

CRT Responders Approximately 70% response rate 30-40% will have objective improvement in LVEF Characteristics of “responders” LBBB with QRS duration > 150 msec QRS to LV pacing site > 110 msec 100% LV pacing Common causes for being a “non-responder” Reduced LV pacing – lead dislodgement, atrial fibrillation, PVC’s Poor LV lead position – anatomy, lead dislodgement Programming issues – suboptimal AV delay or V-V timing

Potential Implant Complications Bleeding / hematoma / bruising Infection Cardiac perforation Pneumothorax Lead dislodgement Diaphragm / Phrenic Nerve stimulation Venous thrombosis Vascular injury Brachial plexus injury Renal failure Arrhythmia induction CVA / MI / Death

Phrenic Nerve Stimulation

Post-Op care Pain relief Monitor typical post-op vital signs Monitor wound – intact, no bleeding, limited swelling at site or arm Monitor for pneumothorax / pericardial effusion / tampanade – sudden chest pain, dyspnea, hypotension, neck vein distention Watch for loss of capture / change in pacing complex / over- and undersensing Monitor for Diaphragm pacing

Conclusions CHF remains a major clinical problem and is responsible for significant CV mortality and repeat hospitalizations CRT has proven to be a significant adjunct to CHF medical therapy resulting in improved in survival and decreased hospitalizations CRT can be performed with high rate of success and low rate of complications Approx 70% will respond to CRT and LVEF will improve in approx 30- 40%. Looking for better ways to identify dyssynchrony and target dyssynchrony LV lead positioning limited by anatomy, scar, diaphragm pacing