The Impact of Patients With Cardiac Amyloidosis in HFpEF Trials

Heart failure with preserved ejection fraction (HFpEF) is an increasingly diagnosed condition whose failure to respond to new drugs effective in heart failure with reduced ejection fraction is of great concern. HFpEF is an incompletely understood and markedly heterogeneous syndrome, but cardiac amyloidosis is increasingly recognized as one of its various causes. The specific hemodynamic and pathophysiological features of cardiac amyloidosis result in poor tolerance of heart failure medications and in worse outcomes compared with other causes. Until recently, patients considered for HFpEF trials were not routinely screened for cardiac amyloidosis. This review examines how real-world patients with cardiac amyloidosis met inclusion criteria for 8 major HFpEF clinical trials, including the recent PARAGON (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction) trial. This review discusses how the presence in the trial populations of a subset of patients with cardiac amyloidosis might contribute to explain the absence of efficacy of medications for HFpEF in trials so far. A multistep screening strategy is suggested in which patients with red flags for cardiac amyloidosis undergo both a light chain assay and technetium-labeled cardiac scintigraphy (technetium-labeled cardiac scintigraphy scan), which, when negative, rule out cardiac amyloidosis. Using this strategy would allow the testing of new medications for HFpEF in populations containing no patients with cardiac amyloidosis, thus potentially increasing the likelihood of showing therapeutic efficacy, and finally making some effective treatment available.