Due to the restrictive physiology, routine use of heart failure guideline-directed medical therapy (including beta blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists and angiotensin receptor/neprilysin inhibitors [ARNI]) are poorly tolerated by patients with cardiac amyloidosis, this intolerance presents a clue to the diagnosis (19). The gene discussed is ACE; the disease is heart failure.