Welcome and Introductions

Welcome and Introductions Nowell Fine MD, SM, FRCPC, FACC, FCCS, FASE, FHFSA 2 Faculty Nowell M. Fine (Chair) MD, SM, FRCPC, FACC, FCCS, FASE, FHFSA Clinical Assistant Professor of Cardiac Sciences and Community Health Sciences Clinical Director, Libin Cardiovascular Institute Director of Echocardiography, Heart Failure Cardiologist Cumming School of Medicine, University of Calgary Calgary, AB Michael Heffernan MD, PhD, FRCPC, FACC Director, Oakville Cardiologists Inc. Staff Cardiologist, Oakville Trafalgar Memorial Hospital Medical Director, Research, Halton Healthcare Assistant Clinical Professor (adj), McMaster University Oakville, ON Margot Davis MD, MSc, FRCPC Clinical Assistant Professor, UBC Cardiology Director, UBC Cardiology-Oncology Program Vancouver, BC 3 Debra Bosley RN, BScN Nurse Clinician/ Cardio-Oncology Clinic Cardiac Sciences, South Health Campus Member of the Canadian Nurses Association and the College of Registered Nurses of Alberta Calgary, AB John Pasternak (Patient) MD Medicine Hat, AB Disclosures: Dr. Nowell Fine •Consultancy/speaking fees: Akcea, Alnylam, Pfizer, Sanofi •Clinical trial participation: Pfizer Disclosures: Ms. Debra Bosley •Consultancy/speaking fees: None •Clinical trial participation: None Disclosures: Dr. Margot Davis •Consultancy/speaking fees: Janssen, Novartis, Boehringer-Ingelheim, Takeda, Pfizer, Akcea, Alnylam, Amgen, Ferring •Grant funding: Pfizer, Takeda, Boehringer-Ingelheim, Servier, Akcea Disclosures: Dr. Michael Heffernan •Consultancy/speaking fees: AstraZeneca, Boehringer Ingelheim, BMS/Pfizer Alliance, Novartis, Pfizer, Sanofi, Servier, Amgen, Bayer, Bristol- Myers Squibb •Clinical trial participation: AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, Amgen, Bayer, Merck •Fiduciary Role: Oakville Cardiologist Inc, Oakville Cardiovascular Research LP •Ownership/Partnership/Principal: Oakville Cardiologist Inc, Oakville Cardiovascular Research LP Disclosures: Dr. John Pasternak •Consultancy/speaking fees: None •Clinical trial participation: Pfizer Disclosure of Commercial Support Specific details of relationship: – This program has received financial support from Pfizer Canada Inc. in the form of an educational grant – This program has received in-kind support from Canadian Heart Failure Society in the form of logistical support Potential for conflict(s) of interest: – Speakers have received honoraria from Canadian Heart Failure Society – Pfizer Canada Inc. is the manufacturer of a product that will be discussed in this program Mitigating Potential Bias Potential biases are acknowledged and are mitigated by presenting data supported by national and international guidelines, and as follows: • Information presented is evidence-based • Material has been developed and reviewed by a Planning Committee Off-label uses of drugs may be discussed and will be identified as such by the speaker Accreditation This event is an accredited Group Learning Activity (Section 1) as defined by the Maintenance of Certification Program of the Royal College of Physicians & Surgeons of Canada and approved by the Canadian Cardiovascular Society. You may claim a maximum of 0.75 hours. Learning Objectives • Recognize the challenges patients face prior to obtaining an ATTR amyloidosis diagnosis and the importance of early diagnosis • Review the clinical presentation, treatment, and guidelines for wild-type ATTR amyloidosis and highlight the importance of a multidisciplinary team approach • Integrate contemporary guidelines and treatment options in the care of patients with wild-type ATTR amyloidosis, whether managed in an academic centre or in community practice 12 Agenda Topic Facilitator Welcome and Introductions Dr. Nowell Fine wtATTR Amyloidosis: A Distinct Disease to Diagnose and Treat Dr. Margot Davis Diving into the Reality of Managing wtATTR Amyloidosis Dr. Nowell Fine Ms. Debra Bosley Dr. John Pasternak (Patient) Managing wtATTR in your Own Clinic Dr. Michael Heffernan Q&A ALL Closing Remarks Dr. Nowell Fine 13 Download the mobile app! Download the app by: 1. Search for and download: CrowdCompass AttendeeHub 2. Find your event: Heart Failure Update Gain access to the: • Congress agenda and session links • Push notifications • Session and symposium evaluation forms • Interactive platform where you can communicate with your fellow attendees! Send in your questions! •Submit your questions for the symposium Q&A by clicking on the Q&A icon on your screen •To direct your question to a specific speaker, please include his/her name at the beginning of your question wtATTR Amyloidosis: A Distinct Disease to Diagnose and Treat Margot K. Davis MD, MSc, FRCPC 16 Epidemiology of wtATTR • Accurate population data are limited • Wild-type disease is far more common than mutant • Estimated that at least 25% of individuals >80 years of age have histological evidence of amyloid deposits in the heart • ATTRwt accounts for ~13% of HFpEF cases in elderly patients (≥60 years old) • Clinical features mimic other cardiac pathologies that frequently co-exist in advanced age, such as hypertensive heart failure and aortic stenosis ATTR, transthyretin amyloidosis; ATTR-CA, transthyretin cardiac amyloidosis; ATTRwt, wild-type form of transthyretin amyloidosis; CA, cardiac amyloidosis; HFpEF, heart failure with preserved ejection fraction; TAVR, transcatheter aortic valve replacement. Connors LH et al. Circulation 2016;133(3):282-290; González-López E et al. Eur Heart J 2015;36(38) 2585-2594; Castaño A et al. Eur Heart J 2017;38(38):2879-2887. Cardiac Manifestations Index of Suspicion – Key Features Pre-contrast T1 Post-contrast T1 ECV LGE • Increased LV and RV wall thickness • Preserved ventricular size, biatrial enlargement • Diastolic dysfunction • Increased valvular and interatrial septum thickness • Small pericardial effusion • Reduced LV GLS, preserved apical strain (basal-apical strain gradient) • Diffuse transmural or subendocardial pattern LGE • Left atrial LGE • Elevated native (non- contrast) T1 mapping time • Extracellular volume expansion (post- contrast T1 mapping) • Low voltage (especially limb leads) • Pseudo-infarct pattern • Atrial fibrillation • Conduction system disease • Ventricular ectopy • Increased myocardial radiotracer uptake equal to or greater than bone (≥Grade 2), or in quantitative comparison with the contralateral lung (HCL ratio ≥1.5) ECG Echo CMRI Tc-99m-PYP Courtesy Dr. James White, Dr. Denise Chan, University of Calgary CCS/CHFS Joint Position Statement Can J Cardiol. 2020 Mar;36(3):322-332 Tc99m-PYP SPECT in Cardiac Amyloidosis Intense diffuse myocardial uptake in a patient with ATTR cardiac amyloidosis, grade 2-3 compared with bone No/minimal myocardial uptake in a patient with AL cardiac amyloidosis, or other causes of LVH ATTR, transthyretin amyloidosis; SPECT, single photon emission computed tomographyTc99m-PYP, 99mtechnetium pyrophosphate. J Am Coll Cardiol, 68(12), Falk RH et al., 1323-1341, (2016) Heart : Contralateral lung ratio >1.5 highly sensitive (>95%) and specific (>85%) for ATTR cardiac amyloidosis ATTR CA AL CA Planar whole body scan With SPECT Tc99m-PYP (Bone) Scintigraphy Enables the Diagnosis of Cardiac ATTR Amyloidosis Without the Need for Histology Study Design • 1217 patients with suspected cardiac amyloidosis • Bone scintigraphy and biochemical investigations AL, light-chain amyloidosis; ATTR, transthyretin amyloidosis; Tc99m-PYP, 99mtechnetium pyrophosphate. Gillmore JD et al. Circulation 2016;133:2404-2412. Results • 857 patients – histologically proven amyloid (374 with endomyocardial biopsies) • 360 patients – nonamyloid cardiomyopathies • Myocardial radiotracer uptake on bone scintigraphy was >99% sensitive and 86% specific for cardiac ATTR amyloid • False positives almost exclusively from uptake in patients with cardiac AL amyloidosis • Combined findings of grade 2 or 3 myocardial radiotracer uptake on bone scintigraphy + absence of a monoclonal protein in serum or urine: • Specificity and positive predictive value for cardiac ATTR amyloidosis: 100% (CI 98.0- 100) Overview of Management Supportive Care in Cardiac Amyloidosis Recommendation • We recommend that heart transplantation be considered for select patients with advanced HF due to cardiac amyloidosis, in whom significant extra-cardiac manifestations are absent and the risk of disease progression is considered low and/or amenable to disease modifying therapy (Strong Recommendation, Moderate-Evidence Quality). Recommendation • In the absence of contraindications, we recommend therapeutic anticoagulation in patients with cardiac amyloidosis and AF, regardless of calculated risk of stroke or systemic embolism. (Strong Recommendation, Low-Quality Evidence). Disease-Modifying Therapy in Cardiac Amyloidosis Recommendation • We recommend tafamidis (if available) for patients with ATTR cardiac amyloidosis and NYHA class I-III symptoms. (Strong Recommendation, High-Quality Evidence). Recommendation • We recommend treatment with a TTR RNA silencing agent (patisiran or inotersen) for patients with hereditary ATTR amyloidosis with ambulatory polyneuropathy (Strong Recommendation, High-Quality Evidence). Summary of Evidence Deficiencies Use of beta blockers, ACE/ARB, MRA, (ARNI), CCB, digoxin Role of liver transplant in era of ATTR disease-modifying therapy Role of LVAD Rate vs. rhythm control Warfarin vs DOAC Role of prophylactic pacemakers Role of CRT Criteria for primary prevention ICD Emerging Therapeutic Targets of the Amyloidogenic TTR Cascade Maurer MS et al. N Engl J Med 2018;379:1007-1016 Randomization, Evaluation, & Outcomes Maurer MS et al. N Engl J Med 2018;379:1007-1016 Primary Analysis and Components Maurer MS et al. N Engl J Med 2018;379:1007-1016 * * Key Secondary End Points CI, confidence interval. Adapted from Maurer MS et al. N Engl J Med 2018; Epub ahead of print doi: 10.1056/NEJM/Moa1805689. Tafamidis: Subgroup Analysis Conclusions • ATTR-CM is an underdiagnosed cause of heart disease • Emerging therapeutic options act at different point in the amyloidogenic TTR cascade: • Silencers: Agents target suppression of amyloidogenic TTR • Stabilizers: TTR-stabilizing agents • Degraders: Removal of already deposited fibrils • Tafamidis is the first HC-approved disease-modifying therapy for wtATTR-CM with the ability to prolong survival and improve symptoms in ATTR patients • Additional therapies and advances in the diagnosis will continue to improve the care of this challenging and complex population ATTR, transthyretin amyloidosis; ATTRm, mutated form of transthyretin amyloidosis; TTR, transthyretin. Q&A 36 Diving into the Reality of Managing wtATTR Amyloidosis Nowell Fine MD, SM, FRCPC, FACC, FCCS, FASE, FHFSA Debra Bosley RN, BScN John Pasternak (Patient) MD 37 Caring for the wtATTR Patient: Clinic and Patient Perspectives 38 Debra Bosley, Nurse Clinician Cardiac Amyloidosis Clinic, University of Calgary • Multidisciplinary ‘team’ approach to patient care • Nurse clinician, cardiologist • Other medical subspecialties – Calgary Amyloidosis Working Group • Referral review and triage • Client phone interview • Review investigations with cardiologist, determine appropriate pre- appointment testing • Imaging, AL urine/serum screening 39 Cardiac Amyloidosis Clinic University of Calgary • Initial appointment • Need for subsequent investigations – genetic testing • Management plan – heart failure care, subspecialty referrals, disease- modifying therapy • Patient/client education o Disease course, subtype, symptoms, progression o Clinic protocols and procedures 40 Cardiac Amyloidosis Clinic University of Calgary • Follow-up care • Monitor and interpret follow-up testing, labs, symptoms • Follow-up on medical subspecialty referrals • Ongoing education and support for clients/families • Liaise and coordinate with research team regarding clinical trials 41 Dr. John Pasternak Family Physician, wtATTR Patient • What are the important considerations from the patient perspective of? • Initial consultation and diagnostic work-up • Follow-up management and care • What other advice do you have for healthcare providers of ATTR patients? 42 Q&A 43 Managing wtATTR in your own Clinic Michael Heffernan MD, PhD, FRCPC, FACC 44 Translating Canadian Guidelines into Practice 45 Implementing The Guidelines At Your Centre 46 Diagnosis: It Begins With An Index of Suspicion If amyloidosis is not in your differential diagnosis you will not make the diagnosis Awareness of the ATTR Red Flags Consider using search algorithms in your EMR to identify patients with Red Flag features that may have been overlooked in the past several years 47 AL Amyloid: Ruling Out A Medical Emergency • AL amyloidosis, a multiorgan disease commonly affecting the kidney, resulting in nephrotic syndrome • Cardiac involvement is the second most common presenting manifestation • Other organ systems that may be involved include • Peripheral and autonomic nervous system • Vasculature • Liver • Gastrointestinal tract • Soft tissues. 48 Untreated, the median survival from onset of heart failure is approximately 6 months, but current therapies can induce a prolonged remission and extend life by many years AL Amyloidosis Screen 49 Screening requisition in your EMR ready for use Immunofixation will reveal an M-protein sFLC will reveal an abnormal kappa-lambda ratio. < 0.26 - monoclonal lambda light chain process > 1.65 - monoclonal kappa light chain process. Diagnosis: Ruling in ATTR 50 Diagnosis: Establishing Cardiac PYP Scanning 51 Radiopharmaceutical and Dose: Tc99m Pyrophosphate / 15-20mCi Imaging Time: 1 hour-post injection May have to image at 2 hours post injection if the heart : contralateral ratio is 1.3-1.6 (equivocal range) and/or the visual grade is 1 or 2 Acquisition: Planars: Anterior, Left Lateral (8min/750kcts/Zoom 1.5) SPECT and gated planars (differentiate between myocardial uptake vs blood pool) should be performed for equivocal studies. Visual Scoring Opacity in cavity excludes blood pool Quantitative Analysis Cardiac PYP: Stepwise Image Analysis • Image quality • Need to see the ribs and sternum clearly • Visual Scan interpretation • Note focal hotspots and agreement with sampling windows • Semi-quantatative interpretation in relation to rib uptake • Grade 0 to 3 • Quantitative scoring of heart to contralateral lung ratio • SPECT analysis for equivocal studies • Rule in or out blood pool false positive Responding to the PYP Result Positive Refer to regional centre for treatment until this is more widely available Would expect local initiation of therapy in the future Equivocal Rescan PYP with SPECT Perform cardiac MRI Biopsy Negative Consider another etiology A full-length variant (Phe64Leu and Thr59Lys) is an important false negative and will require a biopsy if your clinical suspicion is high Diagnosis: Genetic Analysis • A positive ATTR patient will require genetic testing • Genetic tests are readily available (similar to the 23andMe home kit) • Wide regional variation of accessibility to genetic counselling • Recognized mutations (hATTR) and wild type (wATTR) are definitive • Mutations of unknown significance are just that • Input of a geneticist is helpful 56 57 59 Q&A 60 Evaluations and Certificates •Here’s how to access evaluations: •Congress APP: “Evaluation Forms” icon •You’ll also get a notification and email each day with evaluation links •Information regarding certificates to be emailed next week 62 Next Up…A Break •Don’t disconnect!! – Plenary Session #4 is coming up in a few minutes •Remember to complete all evaluations – Go to congress APP or your email • To Download the app: Search CrowdCompass AttendeeHub​; Find Heart Failure Update •Visit the VIRTUAL EXHIBIT HALL on HFupdate.ca - Uber Eats gift cards offered! 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