A 76-year-old man with a medical history of hypertension, hyperlipidemia, type 2 diabetes mellitus, carpal tunnel syndrome, and benign prostatic hypertrophy was recently diagnosed with wildtype transthyretin (ATTR) cardiac amyloidosis with preserved left ventricular ejection fraction of 51% on echocardiography. He does not have a known history of atrial fibrillation or coronary artery disease. He presents due to worsening dyspnea on exertion and to establish care.
Although he was playing tennis on weekends several months prior, over the previous month he has been getting short of breath completing chores around the house and when he bends over. In addition, he has noted some swelling around his ankles and his abdomen has felt bloated. He denies any chest pain, palpitations, or syncope. He has woken up several times overnight feeling short of breath. When he tries to do activities quickly, he becomes short of breath, his legs fatigue, he has to rest, and he cannot keep up with his spouse or his friends.
On examination, his blood pressure is 100/65 mm Hg, heart rate is 68 bpm and regular, and respiratory rate is unremarkable. He is well appearing and in no distress at rest. His jugular venous pressure is elevated to 10-12 cm H2O, heart is regularly in rate and rhythm with a soft grade 2/6 holosystolic murmur at the left lower sternal border, and there is no S3. His lungs show scattered rales at the bases. His abdomen is full without obvious ascites. His extremities show 1+ pitting edema.
His current medications include amlodipine 10 mg daily, metoprolol succinate 50 mg daily, furosemide 20 mg daily, empagliflozin 10 mg daily, metformin 1000 mg BID, spironolactone 25 mg daily, rosuvastatin 10 mg daily, and finasteride 5 mg daily.
Based on this clinical presentation, which one of the following medications could be considered for decreasing or stopping?
Show Answer
The correct answer is: C. Metoprolol succinate
Answer choice C is the correct choice. Patients with cardiac amyloidosis have a small left ventricular cavity with restrictive filling leading to a low, mostly fixed stroke volume. Thus, they are often heart rate dependent and cannot augment their stroke volume to compensate for a lower heart rate. In this patient, his relatively low resting heart rate of 68 bpm suggests that an inability to augment his cardiac output with exercise may be contributing to his functional limitation. Although there are limited data on the use of beta blockers in cardiac amyloidosis, a recent retrospective study of patients with ATTR cardiac amyloidosis showed that deprescribing beta-blockers may lead to improved outcomes.1 Further, several expert consensus statements recommend avoiding beta-blockers in patients with cardiac amyloidosis unless there is a strong indication, as it tends to be poorly tolerated.2-4 In this case, the patient does not have uncontrolled arrhythmias or angina from coronary artery disease, so he does not have a strong indication for his beta-blocker.
Answer choice A is an incorrect choice. Amlodipine is not contraindicated in patients with cardiac amyloidosis and can be considered for management of hypertension. Although amlodipine can sometimes lead to lower extremity edema, his overall physical examination and recent diagnosis of ATTR cardiac amyloidosis suggest fluid overload rather than an adverse effect of the amlodipine as the cause of his lower extremity edema. Conversely, nondihydropyridine calcium channel blockers (e.g., verapamil and diltiazem) should be avoided in patients with cardiac amyloidosis due to the negative chronotropic effects and risk of binding to amyloid fibrils that may lead to hyperphysiologic effects.2,4
Answer choice B is an incorrect choice. There are limited data regarding the use of empagliflozin or other sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with cardiac amyloidosis. Although recent trials have shown benefit of SGLT2 inhibitors in heart failure (HF) with preserved ejection fraction with a reduction in cardiovascular death or hospitalization,5,6 data specific to patients with amyloidosis are not available. However, it may be reasonable to consider SGTL2 inhibitor use for their diuretic properties in patients with cardiac amyloidosis and clinical HF.
Answer choice D is an incorrect choice. There is no particular reason to stop a statin in a patient with cardiac amyloidosis.
Answer choice E is an incorrect choice. Spironolactone should not be stopped. In fact, a recent retrospective analysis of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) data with a subcohort enriched for cardiac amyloidosis based on echocardiographic features (but not with confirmed cardiac amyloidosis) suggested a benefit with use of spironolactone in patients with cardiac amyloidosis.7 Further, because he is on loop diuretics, spironolactone may be beneficial for potassium sparing and sequential nephron blockade. Because he is fluid overloaded on examination, he would benefit from increased loop diuretics and potentially an increase in the spironolactone.
References
Cheng RK, Vasbinder A, Levy WC, et al. Lack of association between neurohormonal blockade and survival in transthyretin cardiac amyloidosis. J Am Heart Assoc 2021;10:doi: 10.1161/JAHA.121.022859.
Kittleson MM, Maurer MS, Ambardekar AV, et al.; American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology. Cardiac amyloidosis: evolving diagnosis and management: a scientific statement from the American Heart Association. Circulation 2020;142:e7-e22.
Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on myocardial and pericardial diseases. Eur Heart J 2021;42:1554-68.
Rapezzi C, Aimo A, Serenelli M, et al. Critical comparison of documents from scientific societies on cardiac amyloidosis: JACC state-of-the-art review. J Am Coll Cardiol 2022;79:1288-1303.
Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 2021;385:1451-61.
Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med 2022;387:1089-98.
Sperry BW, Hanna M, Shah SJ, Jaber WA, Spertus JA. Spironolactone in patients with an echocardiographic HFpEF phenotype suggestive of cardiac amyloidosis: results from TOPCAT. JACC Heart Fail 2021;9:795-802.
Log in to MyACC
