Disclosures: Research support from Philips Research grant & Speaker’s Bureau Astellas Research grant from General Electric Research grant from Myocardial Solutions Off-label use of contrast agents Off-label use of adenosine/ regadenoson

Utility of Cardiac MRI in

Amit R. Patel MD, FACC Associate Professor of Medicine and Radiology Director Cardiac MRI and CT Cardiac Magnetic Resonance: A Multi-Parametric Evaluation Other Myocardial Processes Cine CMR Myocardial Myocardial Scar (LGE)

Myocardial Myocardial Fibrosis Capillary Leak (T1-W) Edema (T2-W) (T1-mapping)

CMR and Heart Failure | 2 The Mother Holter Monitor

• 33 year old woman with no significant past medical history. • Following birth of 2nd child, she developed CHF and palpitations.

EKG

Predominant Rhythm = NSR Occasional PVCs (2% of total QRS complexes) Frequent (noted particularly with symptomatic palpitations) Rare PACs(<1% of QRS complexes) 1 SVT Run (8 beats) No pauses No evidence for AV dissociation or block

CMR and Heart Failure | 3 The Mother: Echocardiogram

Clinical Diagnosis: Peripartum

CMR and Heart Failure | 4 The Mother: Cardiac Magnetic Resonance

Genetic Testing: PKP2 (plakophylin 2) and Asn557Asp, likely Pathogenic. CMR and Heart Failure | 5 Final Diagnosis: Arrhythmogenic Right Ventricular Cardiomyopathy Arrhythmogenic Right Ventricular Cardiomyopathy

• Inherited cardiomyopathy characterized by fibro-fatty replacement of the RV myocardium • Increased risk of ventricular and right heart failure • Typically due to autosomal dominant mutations in desmosomal genes with variable penetrance • Diagnosis - multifaceted approach

– Family history/ genetics Br Heart J 1994;71:215-218 – Electrocardiogram/ rhythm abnormalities – Tissue characterization from RV myocardial biopsy – RV dysfunction & structural alterations from imaging • RV angiography • Echo • Cardiac MRI

• CMR is the imaging modality of choice to evaluate ARVC because of its ability to assess RV morphology and function

CMR and Heart Failure | 6 Misdiagnosis of ARVC using CMR Butterfly Apex

More than 70% of patients referred to ARVC center were incorrectly diagnosed and did not meet criteria

RV-Sternum Tethering Inferior

Superior

CMR and Heart Failure | 7 te Riele. JCMR 2014 Mimics of Arrhythmogenic Right Ventricular Cardiomyopathy Unmasked with CMR

Partial Congenital Pectus Excavatum Secundum Type Atrial Septal Defect Absence of

Pectus Carinatum Breast Implants Pulmonary Hypertension

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Quarta. JCMR 2013 Mimics of Arrhythmogenic Right Ventricular Cardiomyopathy Unmasked with CMR

Cardiac Sarcoidosis

Myocarditis Anomalous Pulmonary Vein

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Quarta. JCMR 2013 Diagnosing Arrhythmogenic Right Ventricular Cardiomyopathy

CMR Task Force Criteria ENTRY Criteria – Regional RV akinesia or dyskinesia or dyssynchronous RV contraction – AND one of following

MAJOR Criteria – RVEDV/ BSA ≥110ml/m2 (male) or ≥100ml/m2 (female) – RVEF ≤40%

MINOR Criteria – RVEDV/ BSA 100-110ml/m2 (male) or 90-100ml/m2 (female) – RVEF 40-45%

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te Riele. JCMR 2014 Quantifying RV Size and Function Using CMR

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Addetia: Circ Imag 2014 Inclusion of Tissue Characterization Using CMR May Increase Diagnostic Sensitivity for ARVC

India Ink Sign

LGE

No Task Force Criteria Met

LGE

India Ink Sign

LGE Minor Task Force Criteria Met T1-signal

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Aquaro. AJC 2016 Structural Stage of ARVC Predicts Arrhythmic Risk

CMR and Heart Failure | 13 te Riele. JACC 2013 The “El” Conductor Electrocardiogram

• 70 year old man with sarcoidosis presents with dyspnea on exertion, palpitations, and chest pain • Past Medical History – Diabetes – Hypertension – Hyperlipidemia – Sarcoidosis (orbital and pulmonary)

CMR and Heart Failure | 14 The “El” Conductor:

CMR and Heart Failure | 15 Screening Strategy for Cardiac Sarcoidosis: HRS Consensus Statement

Late Gadolinium Enhancement

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Birnie. HRJ 2014 Detection Strategies and Outcomes for Cardiac Sarcoidosis

• 321 patients with biopsy proven extra-cardiac sarcoid • Screening with symptoms, ECG, Holter, TTE, and CMR with LGE • Outcomes: all-cause death, sustained , and hospitalization for CHF • 30% of patients had LGE/ “cardiac sarcoid” – Really myocardial damage of “some sort” • Median follow up 7 years – 7.2% had major event (hazard ratio 5.68)

Sensitivity Specificity • Presence of LGE is an independent predictor of events – >25% event rate (4% per year) Symptoms 65% 57% ECG 21% 81% • Echocardiography of limited prognostic value when added to symptoms and ECG Holter 59% 58% TTE 27% 98%

CMR 97% 100%

CMR and Heart Failure | 17 Kouranos. JACC Imaging 2017 CMR for the Evaluation of Cardiac Sarcoidosis: A Meta-Analysis

Predicting Composite Outcomes

CMR and Heart Failure | 18 Coleman. JACC Imaging 2016 Imaging-Guided Immunosuppressive Therapy

Cardiac MRI FDG PET After 6 Weeks of Prednisone

Cardiac MRI FDG PET

CMR and Heart Failure | 19 Detection of Inflammation Using CMR: T1 and T2-mapping

• 53 patients with extra-cardiac sarcoid and 36 volunteers • CMR with LGE and T1- and T2-mapping • Repeat imaging in subset of 40 patients – 18 with anti-inflammatory tx – 22 without anti-inflammatory tx • Sarcoid patients had higher T1 and T2 than controls • Patients who underwent treatment had significant reduction in T1 and T2 Puntmann. Radiology 2017

Crouser. J Invest Med 2016

CMR and Heart Failure | 20 Cardiac MRI in Patients with ICD

CMR and Heart Failure | 21

Singh. ACC 2017 The “El” Conductor: Late Gadolinium Enhancement Base Apex

Diagnosis: (aTTR) Treatment Plan: - Diuretics - ?Doxycycline - ?Diflunisol - ?Tafamidis - ?Patisiran or ?Revusiran - ?Green Tea Extract

CMR and Heart Failure | 22 Prevalence of Echo Abnormalities in Cardiac Amyloidosis

172 Patients with Cardiac Amyloidosis

The “El” Conductor

CMR and Heart Failure | 23

Quarta. Circulation 2012 Prevalence of Cardiac Amyloidosis in Elderly Patients with

• 113 patients with significant aortic stenosis referred for CMR – Median age 74 years • 16% of patients had evidence of cardiac amyloidosis – If only considering men, 32% had cardiac amyloidosis • 7 of 9 patients with cardiac amyloidosis had low flow/ low gradient AS • Mortality in patients with aortic stenosis w/ cardiac amyloidosis was significantly greater than those with AS w/o cardiac amyloidosis (56% vs 20%)

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Cavalcante. JCMR 2017 Amyloidosis and Cardiac MRI: Late Gadolinium Enhancement

• Interstitial myocardial expansion by deposition of insoluble amyloid fibrils originating from misfolded protein

• Presence of circumferential LGE on CMR had sensitivity 80%, specificity 94%, PPV 92%, and NPV 85% when compared to endomyocardial biopsy

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Vogelsberg. JACC 2008 Selvanayagam. JACC 2007 Risk Stratification Using LGE in Cardiac Amyloidosis

• 250 prospectively recruited patients – 122 with aTTR Amyloid – 119 with AL Amyloid • Mean follow up 24 months; 27% died • Transmural LGE predicted death with hazard ratio 5.4 [CI: 2.1-13.7] • Findings independent of nt-proBNP, LVEF, E/e’, LV mass index

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Fontana. Circulation 2015 Monitoring Response to Therapy

• 31 patients with AL cardiac amyloid • Serial testing before and after chemotherapy • Baseline: LGE present in 84% and ECV 54±11% • Remission rates: Complete 36%, Very good partial 29%, Partial or none 39% • Regression (decrease in ECV>2 std dev) occurred in 92% of patients with complete or very good partial remission

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Martinez-Naharro. iJACC 2017 37 year old with Sickle Cell Thalessemia T2* Imaging

TE 2.6ms TE 4.9ms TE 7.2ms

• Admitted for congestive heart failure (LVEF 30%) and ventricular tachycardia.

• Past medical history significant for:

– Sickle cell disease requiring TE 9.5ms multiple blood transfusions TE 11.8ms TE 14.1ms

– Atrial

– Chronic DVT

– Diabetes Mellitus

T2* Myocardium = 12ms

CMR and Heart Failure | 28 Myocardial Iron Overload and Ventricular Tachycardia: Independent of Systolic and Diastolic Function

• Moderate relationship between T2* and LVEF (r=0.52) • No relationship between E/A, E’, E/E’, or Tei index

CMR and Heart Failure | 29 Wood. Blood 2004 Leonardi. JACC Imaging 2008 T2* and Cardiovascular Outcomes

CMR and Heart Failure | 30

Kirk. Circulation 2009 T2*-Guided Therapy Improves Outcomes in Thalessemia

Introduction of Cardiac T2* CMR and Heart Failure | 31 Modell. JCMR 2008 The Accountant

• 62 year old man with easy fatiguability and palpitations • Review of systems: – Hypohydrosis • Past Medical History: – – (paroxysmal) • Family history – Paternal grandfather, father, paternal uncles x2 all died suddenly at young age LVEF: 70% • Exam with normal blood pressure, no JVD, no edema, normal IVSt: 19mm heart sounds E: 82 cm/sec A: 45 cm/sec • EKG with severe LVH with ST/T changes Decel Time: 0.17 sec E/A: 1.8 e’: 5 cm/sec E/e’: 16.4 GLS -6.8% Clinical Diagnosis: Hypertrophic Cardiomyopathy CMR and Heart Failure | 32 The Accountant

LGE 4-Chamber LGE 2-Chamber Native T1: 870ms Final Diagnosis: Atypical Variant Fabry’s Disease CMR and Heart Failure | 33 Native T1 Relaxation Times Are Reduced in Fabry Disease

Healthy Fabry w/o LVH

Fabry w/ LVH Mean T1= Mean T1= Mean T1= 904±46ms 853±50ms 968±32ms

CMR and Heart Failure | 34

Pica JCMR 2014 54 year old woman with a few days of intermittent chest pain

LAD Occlusion LAD Stent P A P T I N E T

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Cardiac MRI: Cine Imaging - 1 Month Later P A P T I N E T

CMR and Heart Failure | 36 Gadolinium Kinetics and Coronary Artery Disease

Contrast Injection Normal Myocardium

Infarcted Myocardium

Ischemic Myocardium

Dynamic First Pass Perfusion Late Gadolinium Enhancement/ Scar (<1 min) (>5 min)

CMR and Heart Failure | 37 Gadolinium Distribution and

Healthy Myocardium Acute Myocardial Infarction Chronic Myocardial Infarction (Intact Cell Membranes) (Ruptured Cell Membrane) (Collagen Matrix)

CMR and Heart Failure | 38

Kim. Cardiovascular MRI and MRA 2003 Detection of Myocardial Scar Using CMR: Late Gadolinium Enhancement

CMR and Heart Failure | 39

Kim. Circulation 1999 Transmurality of Myocardial Infarction and Viability

CMR and Heart Failure | 40

Kim. NEJM 2000 Redefining Hibernating Myocardium: Assessment of Myocardial Scar Not Wall Thickness

201 patients with regional thinning spanning on average ~1/3 of LV surface area Extent of scar in thinned segments was ~ 70% ~1/5th of thinned segments had <50% scar extent

CMR and Heart Failure | 41

Shah. JAMA 2013 Myocardial Fibrosis Predicts Prognosis in • 472 patients w/ dilated CMP • 142 patients w/ midwall fibrosis • Median follow up 5.3 years • Patients w/ midwall fibrosis were more likely to die (27% vs 11%) and have arrhythmic event (30% vs 7%) • Findings independent of LVEF

CMR and Heart Failure | 42

Gulati. JAMA 2013 Presence of Myocardial Fibrosis Predicts Response to Therapy

• 51 patients with newly diagnosed dilated cardiomyopathy (EF<45%)

• Late gadolinium enhancement imaging, echo, 6MWT, cardiopulmonary exercise, and ntBNP

• LV function reassessed after 5 months of optimal medical therapy

• 24% of DCM patients had LGE

• Fibrosis mass independently associated with change in LVEF following medical therapy

CMR and Heart Failure | 43

Leong. Eurpoean Heart Journal 2012 Late Gadolinium Enhancement Predicts Response to Resynchronization Therapy

• at LV pacing sites leads to incomplete resynchronization • 559 patients with heart failure (ischemic and non- ischemic) • Implantation was either guided or not guided by LGE- CMR prior to implantation – CMR w/ LGE: HR 6.34 – CMR w/o LGE: HR 1.0 – No CMR: HR 1.51

CMR and Heart Failure | 44

Leyva. JCMR 2011 Scar Burden Better Predicts Need for ICD Therapy

CMR and Heart Failure | 45

Klem. JACC 2012 Summary

• Cine CMR is an accurate technique for quantifying left and right ventricular function

• CMR add significant clinical value by more allowing for a more accurate diagnosis

• LGE CMR allows for the characterization of the myocardial tissue –Myocardial Viability –Risk Stratification –Guidance of Therapy

CMR and Heart Failure | 46 Patel. JACC Imaging 2017 Thank you [email protected]

CMR and Heart Failure | 47