Cardiac Amyloidosis and its New Clinical Phenotype: Heart Failure with Preserved Ejection Fraction

Abstract

Heart failure with preserved ejection fraction (HFpEF) is now an emerging cardiovascular epidemic, being identified as the main phenotype observed in clinical practice. It is more associated with female gender, advanced age and comorbidities such as hypertension, diabetes, obesity and chronic kidney disease. Amyloidosis is a clinical disorder characterized by the deposition of aggregates of insoluble fibrils originating from proteins that exhibit anomalous folding. Recently, pictures of senile amyloidosis have been described in patients with HFpEF, demonstrating the need for clinical cardiologists to investigate this etiology in suspect cases. The clinical suspicion of amyloidosis should be increased in cases of HFPS where the cardio imaging methods are compatible with infiltrative cardiomyopathy. Advances in cardio imaging methods combined with the possibility of performing genetic tests and identification of the type of amyloid material allow the diagnosis to be made. The management of the diagnosed patients can be done in partnership with centers specialized in the study of amyloidosis, which, together with the new technologies, investigate the possibility of organ or bone marrow transplantation and also the involvement of patients in clinical studies that evaluate the action of the new emerging drugs.

Cardiac amyloidosis: An update on diagnosis and treatment

“…LV wall thickness greater than 12 mm (6 mm to 10 mm is normal) in the absence of hypertension should prompt suspicion for CA. 34 LV thickening most often appears symmetric; however, occasionally it may exhibit asymmetric septal hypertrophy, particularly in ATTRwt-CA. In some cases, there may be a smaller subset that can actually have dynamic LV outfl ow obstruction similar to that seen in hypertrophic obstructive cardiomyopathy.…”

“…This explains why patients with CA cannot usually tolerate reduced heart rates, as their cardiac output is dependent on heart rate. [34][35][36]…”

“…Because of the thickened ventricles, patients can often be misdiagnosed as having HCM with or without obstruction. 7,34 The fi rst manifestation of CA may be atrial fi brillation, most commonly in ATTRwt-CA, or cardioembolic stroke. Atrial fi brillation can be present for years before CA is considered.…”

“…Because light chains are excreted by the kidney, the serum levels of both kappa and lambda will be elevated in renal dysfunction, but the ratio should remain normal. 16,31,34,40,[42][43][44][45][46][47]…”

“…A combination of loop diuretics and an aldosterone antagonist is most effective. 31,34,44,45 Torsemide is preferred over furosemide due to its superior bioavailability and longer duration of action, particularly since these patients have issues with gut edema and GI absorption. Due to dependence of the cardiac output on heart rate and the tendency for orthostatic hypotension, traditional neurohormonal antagonists including beta blockers and angiotensin-converting enzyme inhibitors are neither effective nor well tolerated.…”