Abstract Introduction Hereditary transthyretin amyloidosis (h-ATTR) is a complex, systemic infiltrative disease characterized by extracellular deposition of transthyretin in different organs. Infiltrative cardiomyopathy and polyneuropathy represent two of the most common and severe manifestations of this pathology. Patisiran is a double-stranded interfering RNA drug, used to stop expression of TTR in h-ATTR. It is recommended in the treatment of cardiac h-ATTR with polyneuropathy or polyneuropathy alone. Recent studies showed the efficacy of Patisiran in slowing the progression of the disease, improving myocardial deformation indices, biomarkers and functional capacity. Aim We aimed to illustrate the efficacy of Patisiran on myocardial function and to evaluate the role of Speckle Tracking Echocardiography (STE) and Cardiac Magnetic Resonance (CMR) as markers of subclinical cardiac efficacy of Patisiran in two h-ATTR patients (males, with mean age 55 ± 1,4 years old) with infiltrative cardiomyopathy and polyneuropathy who were scheduled to receive this drug. Materials and Methods Before receiving Patisiran (T0) the following tests were performed: cardiovascular physical examination, complete echocardiogram including STE. All these exams were repeated after 6 months or 1 year (T1). CMR was performed at the baseline and three years after. Results The CMR evaluation showed, after the use of Patisiran, a significant reduction of myocardial mass (average reduction -13,29%) and myocardial walls thickness (average septal reduction -13,65%). After 1 year follow up myocardial performance indices were also improved: GLS values (average gain 2,3 pt), and myocardial work values (average increase GWI +311,5, GCW +188,5, GWW -114,5, GWE +5,5 pt) at echocardiography. Conclusion The results of our experience showed, according to evidences suggested by the APOLLO trial, the efficacy of Patisiran, in patients with cardiac h-ATTR and polyneuropathy, in reducing myocardial mass and improving myocardial function. STE and CMR could represent useful tools to study cardiac function in A-TTR patients undergoing Patisiran.