P218 WILD TYPE TRANSTHYRETIN CARDIAC AMYLOIDOSIS (WTATTR) AND HEART FAILURE WITH REDUCED EJECTION FRACTION (HFREF): CAN ANGIOTENSIN RECEPTOR/NEPRILYSIN INHIBITORS (ARNI) BE A THERAPEUTIC OPTION?

Abstract

Abstract Background wtATTR is associated with high mortality rate, median survival from diagnosis is 43 months and mortality reaches 50% at 4 years. Most patients (pts) present with heart failure and preserved ejection fraction (HFpEF), fewer with HFrEF. Tafamidis is the only modifying–disease agent available in Italy and therapeutic strategy is based on diuretic titration. Beta blockers and therapies for neurohormonal antagonism have raised concerns about their efficacy and safety. The role of ARNI has not been explored. We report our experience of the use of ARNI in pts with wtATTR not eligible to Tafamidis due to advanced NYHA classes. Cases 4 male pts (median age 81 y.o.) received diagnosis of wtATTR between 2018 and 2019 when Tafamidis was not available. Median left ventricular ejection fraction (mLVEF) at the time was 51%. 2 years later they presented with acute HFrEF (Tab1–T0), NYHA classes III–IV with median systolic blood pressure 105 mmHg. Average N–terminal pro natriuretic peptide (NTproBNP) levels were 13888pg/ml and median estimated glomerular filtration rate (eGFR) was 36 mil/min/1,72m2. mLVEF was 23%. Once congestion was relieved pts started Sacubitril/Valsartan (S/V) with titration of dose. At 6 months follow–up (FU) (Tab1–T1) pts were downgraded to NYHA class II and no symptomatic hypotension was reported. Average NTproBNP levels were reduced to 7.800pg/l, only mild worsening of renal function was reported (median eGFR 31mil/minx1.73m2). Absolute increase of mLVEF (46%) was shown on echocardiography. At 12 months FU (Tab 1–T2) pts were clinically stable in NYHA class II, NTproBNP median values had mildly increased to 9700pg/ml and average eGRF was stable (30mil/minx1.73m2). Echocardiogram highlighted minimal reduction of mLVEF compared to previous result (41%). During FU only 1 of the pts required hospitalization for intravenous diuretic therapy and S/V was temporarily suspended. Conclusion The efficacy of S/V in HFrEF is well known. Our brief study proves that ARNI can be tolerated in frail pts affected by wtATTR with no other therapeutic options, guaranteeing a long hospitalization–free period with improvement in quality of life. The result may be purely due to the natriuretic effect of ARNI in patients so strictly reliant on volemic state. More complicated effects may be mediated by neprilisin on amyloid protein; further studies are warranted to establish the role of ARNI in wtATTR.