U.S. Department of Health and Human Services National Institutes of Health National Heart, Lung, and Blood Institute Quantitative Assessment of Congestive Heart Failure with Noninvasive Imaging: Background and Current Approaches Jonathan F. Plehn, M.D. NIH/NHLBI Cardiovascular Branch

Congestive Heart Failure (CHF): A Syndrome of Epidemic Proportions Approximately 4.9 million cases in the United States today Approximately 4.9 million cases in the United States today Over 400,000 new cases per year Over 400,000 new cases per year The most common cause of hospitalization in people over 65 years The most common cause of hospitalization in people over 65 years Increasing numbers of CHF patients due to the aging population Increasing numbers of CHF patients due to the aging population

Cardiomyopathy : disease of cardiac muscle disease of cardiac muscle can be symptomatic or asymptomatic can be symptomatic or asymptomatic Congestive Heart Failure (CHF): inability of the heart to meet the body’s metabolic demands inability of the heart to meet the body’s metabolic demands manifest by manifest by  Forwards failure: weakness, fatigue  Backwards failure: dyspnea (shortness of breath), peripheral edema (leg swelling)

Systolic Heart Failure: reduced LV contractility (EF <40%) Diastolic Heart Failure: preserved EF (>40%), delayed LV relaxation and increased chamber stiffness

Noninvasive Imaging of Cardiac Function Echocardiography (2D/M-mode, 3D, Doppler)Echocardiography (2D/M-mode, 3D, Doppler) Radionuclide Cineangiography (MUGA, gated SPECT)Radionuclide Cineangiography (MUGA, gated SPECT) Magnetic Resonance ImagingMagnetic Resonance Imaging Contrast Left Ventriculography (Cath)Contrast Left Ventriculography (Cath) CT AngiographyCT Angiography

Normal Systolic Function Severely Depressed Systolic Function

LV Remodeling ACE Inhibitors ACE Inhibitors ARBs ARBs Beta Blockers Beta Blockers Survival ACE Inhibitors ACE Inhibitors Beta Blockers Beta Blockers Hydralazine/Isordil Hydralazine/Isordil Aldactone (Class II-IV) Aldactone (Class II-IV)Symptoms Diuretics Diuretics Digoxin Digoxin ACE Inhibitors ACE Inhibitors ARBs ARBs Beta Blockers Beta Blockers

Regional Wall Stress: Finite Element Analysis

After Kass D. New dimensions in device-based therapy for heart failure–mechanisms of stimulation for heart failure. Heart Failure Society of America Left Bundle Branch Block Sinus node AVnode His Bundle Left Bundle Branch

Normal Left Bundle Branch Block

Prevalence of LBBB in Heart Failure 1. Masoudi, et al. JACC 2003;41: Aaronson, et al. Circ 1997;95: Normal LVEF 8% Impaired LVEF24% NYHA Class III-IV38%

Association of QRS Duration on Survival in VEST QRS Duration (msec) < >220

MRI Tissue Tagging with SPAMM Yeon et al. JACC 2001;38

Normal LV Phasic Contraction Nelson GS et al. Circulation 2000;101

Abnormal Phasic Contraction: Dilated Cardiomyopathy Nelson GS et al. Circulation 2000:101

Forms of Cardiac Dyssynchrony in Heart Failure Intra-ventricular: septal/lateralIntra-ventricular: septal/lateral Inter ventricular: LV/RVInter ventricular: LV/RV Atrio-ventricular: (atrial booster pump)Atrio-ventricular: (atrial booster pump)

Sinus node AVnode Kass D. New dimensions in device-based therapy for heart failure–mechanisms of stimulation for heart failure. Heart Failure Society of America BIVENTRICULAR PACING THERAPY Biventricular Pacing

Bi-ventricular Pacing 1) 1)Right atrium: AV synchrony 2) 2)Right ventricle: Inter-ventricular synchrony 3) 3)Left ventricle: Intra-ventricular synchrony Doug Smith: Right Atrial Lead Right Ventricular Lead Left Ventricular Lead

Benefits of CRT in CHF 1.Improved Exercise Capacity (treadmill, 6 minute walk) 2.Increased Quality of Life (questionaires) 3.Improved Survival 4.LV Reverse Remodeling, Increased LV Ejection Fraction 5.Reduction in Neurohormone Levels 6.Reduction in Mitral Regurgitation 7.Increased Heart Rate Variability 8.Reduction in Myocardial Oxygen Consumption (energetics) 9.Improvement in LV Stroke Work

The Next Step Beyond Drug Therapy

Downsides of CRT in CHF 1.Device is expensive 2.Implantation is time-consuming and sometimes unsuccessful 3.Occasional complications (e.g. tamponade)

Unresolved Issues in CRT At least 20-30% of patients with wide QRS complexes are non-responders:At least 20-30% of patients with wide QRS complexes are non-responders: –No dyssynchrony –Inadequate pacing site –Too much pump damage at baseline QRS width correlates only roughly with mechanical dyssynchronyQRS width correlates only roughly with mechanical dyssynchrony Dyssynchrony in patients with normal QRS widths or right bundle branch block. These may respond to CRTDyssynchrony in patients with normal QRS widths or right bundle branch block. These may respond to CRT

MRI Dysynchrony Index Predicts Improvement with Resynch Pacing Nelson GS et al. Circulation 2000;101

2D-Guided M-mode Echo

Before CRT Bi-V Pacer Firing Segmental Wall Motion Analysis: 2D Echo

3DEcho

3D Echo Segmental Wall Motion Analysis

Doppler Tissue Imaging: Sampling Velocities of Single Points Doppler Strain Rate Imaging: Sampling Differences Between Two Points D’hooge J et al. Eur J Echo 2000;1

Doppler Tissue Velocity Imaging Doppler Strain Rate Imaging

Radionuclide Cineangiography

Current Limitations of Noninvasive Dyssynchrony Evaluation Approach is usually tomographic (1 or 2D) leading to limitation in spatial quantitationApproach is usually tomographic (1 or 2D) leading to limitation in spatial quantitation Data is noisyData is noisy Quantitative analysis is time-consumingQuantitative analysis is time-consuming Inter-observer variability in the community is unknownInter-observer variability in the community is unknown