Cardiac amyloidosis: An emerging target in HFpEF? Peter van der - PowerPoint PPT Presentation

Cardiac amyloidosis: An emerging target in HFpEF? Peter van der Meer, MD Groningen, The Netherlands May, 2019 - Athens, Greece

Amyloidosis Cardiac amyloidosis: An emerging target in HFpEF? Peter van der Meer Universitair Medisch Centrum Groningen University Medical Center Groningen

Amyloidosis History + Medication • Male patient, 74 years old. • Medical history: hypertension + depression • Home medications: - Metoprolol succ 50mg once daily - Paroxetine 20mg once daily University Medical Center Groningen

Amyloidosis What happened • Walking with friends • Suddenly shortness of breath • Denies chest pain and palpitations • Can normally bike 70-80km without any problems • Ambulance brings patient to ER University Medical Center Groningen

Amyloidosis Physical Examination Weight: 104kg Height: 182cm BMI: 31.4 BP: 150/82 mmHg, Heart: 55 bpm, no murmers Lungs: crepitus basal both lungs Extremities: Trace peripheral edema, pulses & neuro intact Lab values: Hemoglobin: 8.1 mmol/L NTproBNP: 2.058 ng/L eGFR: 48 ml/mn/1.73 hsTroponin T: 38 ng/L University Medical Center Groningen

Amyloidosis ECG SR 65 bpm, 1st degree AV block qs-pattern V1-3 and + lateral QRS: 131ms Rightward axis University Medical Center Groningen

Amyloidosis Chest X-ray University Medical Center Groningen

Amyloidosis Trans Thoracic Echocardiogram University Medical Center Groningen

Amyloidosis Trans Thoracic Echocardiogram E' - lat 4.6 cm/s E' - sept 3.5 cm/s E/e' 19.8 University Medical Center Groningen

Amyloidosis Summary of echocardiography findings • Hypertrophic LV (septal:29mm), (pw: 25mm) • LVEF: 57%. Severely impaired diastolic LV function • Hypertrophic RV; RV free wall: 10mm. • No significant valvular abnormalies. • Enlarged left and right atrium. University Medical Center Groningen

Amyloidosis Bone Scintigraphy Tc-99m HDP 0 1 2 3 Visual grading score Patient University Medical Center Groningen

Amyloidosis Additional investigations Coronary Angiogram: No Coronary Artery Disease Fat biopsy Genetics Congo Red positive staining. WES TTR gene: no mutations University Medical Center Groningen

Amyloidosis Diagnosis Heart Failure with Preserved Ejection fraction based on wild-type aTTR amyloidosis University Medical Center Groningen

Amyloidosis Search for Specific etiologies of HFpEF University Medical Center Groningen

Amyloidosis Treatment options for ATTR-cardiomyopathy Jono et al. Exp. Opinion on Orphan drugs 2017 University Medical Center Groningen

Amyloidosis ATTR-ACT Study Design NEJM 2018 University Medical Center Groningen

Amyloidosis All-Cause Mortality ^ University Medical Center Groningen

Amyloidosis Effects of tafamidis on 6 MWT and different subgroups University Medical Center Groningen

Amyloidosis Other novel treatment option: RNA therapeutics University Medical Center Groningen

Amyloidosis APOLLO trial – Patisiran; RNA based treatment Hereditary TTR Substudy on cardiac effects Decrease = LVWT < 2mm Solomon et al. Circulation 2019 University Medical Center Groningen

Amyloidosis Conclusions • Search for the etiology of HFpEF (aTTR / Fabry / atypical HCM / etc) • Bone scintigrafy has a high sensitivity and specificity for aTTR • AL needs to be excluded • Genetic testing to exclude heriditary form • aTTR = first steps in personalized medicine in HFpEF (tafamidis – patisiran) University Medical Center Groningen