Cardiac Amyloidosis Guidelines

Updated: Mar 25, 2020
  • Author: Gyanendra K Sharma, MD, FACC, FASE; Chief Editor: Terrence X O'Brien, MD, MS, FACC  more...
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Guidelines Summary

In February 2020, the Canadian Cardiovascular Society (CCS) and Canadian Heart Failure Society (CHFS) released their recommendations on selected topics of high clinical relevance in the management of heart failure (HF). [76] These guidelines incorporate new evidence from randomized clinical trials published after 2017.

Percutaneous Mitral Valve Repair for HF and Reduced Ejection Fraction and Severe Functional Mitral Regurgitation

The CCS/CHFS recommends maximally tolerated guideline-directed medical therapy (GDMT), including cardiac resynchronization therapy and revascularization where appropriate, be implemented before consideration of percutaneous mitral valve repair (PMVR) for patients with HF and reduced ejection fraction (HFrEF) and severe functional mitral regurgitation (FMR) (strong recommendation).

It is suggested that patients with symptomatic HF (HFrEF) despite maximal GDMT and severe mitral regurgitation be evaluated for PMVR (weak recommendation).

The CCS/CHFS recommends that a multidisciplinary dedicated heart team (including interventionalists, cardiac surgeons, imaging specialists, and HF specialists) evaluate and manage the care of potential candidates for PMVR (strong recommendation).

Practical tips

Use caution when treating FMR in patients with HFrEF.

Patients with HFrEF and FMR who have severe left ventricular (LV) dilatation (typically LV end diastolic dimension >70 mm) and less than severe mitral regurgitation may be poor candidates for PMVR with MitraClip.

Patients with FMR should first receive maximally tolerated GDMT, including pharmacologic and nonpharmacologic HF therapies (eg, cardiac resynchronization therapy where applicable) for a reasonable minimum period (eg, 3 months), before PMVR is considered.

Refer patients considered for PMVR to centers experienced in evaluating patients with advanced HF, have high volumes of patients with valve disease managed medically and surgically, and have a high likelihood of achieving the volume of PMVR (eg, 2-4 per month) required for developing and maintaining competence in well-selected patients.

Treatment of Cardiac Amyloidosis

When cardiac amyloidosis (CA) is suspected, rule out light-chain amyloidosis (AL amyloidosis) using serum free light chains (kappa and lambda), and serum and urine protein electrophoresis with immunofixation. Accurate identification of the amyloid subtype is essential to initiate specific treatment and avoid inappropriate application of therapy.

Practical tips

In the setting of undifferentiated CA, the presence of light chains does not confirm the diagnosis of light chain cardiac amyloidosis (AL-CA) because monoclonal gammopathy of unknown significance and transthyretin cardiac amyloidosis (ATTR-CA) can coexist. In such settings, tissue biopsy is often necessary to exclude AL-CA.

Perform technetium-labeled scintigraphy, where available, to diagnose ATTR-CA when plasma cell dyscrasias have been ruled out.

Patient selection for tafamidis, a transthyretin tetramer stabilizer, should reflect the inclusion criteria for the Transthyretin Amyloidosis Cardiomyopathy Trial (ATTR-ACT) that showed clinical benefits of tafamidis over placebo with respect to mortality and cardiovascular hospitalization, including established ATTR-CA and objective evidence of HF (with elevated natriuretic peptides, where available).

Do not routinely consider treatment with tafamidis for patients with New York Heart Association (NYHA) class IV symptoms or severe functional disability, measured using a 6-minute walk test < 100 m. (These patient were excluded from ATTR-ACT.) Subgroup analysis from the ATTR-ACT trial suggested that the reduction in cardiovascular hospitalizations seen with tafamidis might be limited to patients with less severe symptoms (NYHA class I or II).

Because of the complexity in diagnosing CA and the potential for offering advanced or experimental treatment options, consider referring patients with CA to experienced centers. Other agents are currently under investigation, which might modify current treatment recommendations.

New Evidence for Angiotensin Receptor Neprilysin Inhibitors in HFpEF

The Prospective Comparison of ARNI (angiotensin receptor-neprilysin inhibitors) with ARB (angiotensin-receptor blockers) Global Outcomes in Heart Failure With Preserved Ejection Fraction (PARAGON-HF) trial, which compared sacubitril/valsartan with valsartan in HFpEF patients, showed a modest but nonsignificant 13% reduction in the primary outcome of first and recurrent HF hospitalizations and cardiovascular death. A secondary end point analysis revealed improvement in quality of life and renal function, which suggested potential benefits with sacubitril/valsartan compared with valsartan. The data further suggest heterogeneity in the treatment response with greater benefit in women and in individuals with a lower LVEF.

The CCS/CHFS indicate that the statistically negative results of the primary end point analysis preclude any recommendation for the general use of sacubitril/valsartan in patients with HFpEF.

New Evidence for SGLT2 Inhibitors and HF

The CCS/CHFS recommend use of SGLT2 inhibitors (eg, empagliflozin, canagliflozin, dapagliflozin) for treatment of patients with type 2 diabetes and atherosclerotic cardiovascular disease to reduce the risk of HF hospitalization and death (strong recommendation).

SGLT2 inhibitors, such as dapagliflozin, are recommended for use in patients with the following features:

  • Type 2 diabetes, aged >50 years, with additional risk factors for atherosclerotic cardiovascular disease, to reduce the risk of HF hospitalization (strong recommendation)

  • Mild to moderate HF due to reduced LVEF (≤ 40%) and concomitant type 2 diabetes, to improve symptoms and quality of life and to reduce the risk of hospitalization and cardiovascular mortality (strong recommendation)

  • Mild to moderate HF due to reduced LVEF (≤ 40%) and without concomitant diabetes, to improve symptoms and quality of life and to reduce the risk of hospitalization and cardiovascular mortality (conditional recommendation)

The CCS/CHFS recommend SGLT2 inhibitors, such as canagliflozin, be used in patients aged >30 years with type 2 diabetes, and macroalbumineric renal disease, to reduce the risk of HF hospitalization and progression of renal disease (strong recommendation).

Practical tips

Note that SGLT2 inhibitors are currently contraindicated for patients with type 1 diabetes.

The most common adverse effects of SGLT2 inhibitors are genital mycotic infections (GMIs), with the highest risk in women (10%-15% risk), those with previous GMIs, and uncircumcised men. GMIs can generally be managed with antifungal drugs and do not require discontinuation of therapy.

SGLT2 inhibitors might result in an up to 15% temporary reduction of estimated glomerular filtration rate (eGFR) (usually resolves within 1-3 months). These drugs have also been associated with acute kidney injury, and increased monitoring is warranted in those at risk.

SGLT2 inhibitors do not cause hypoglycemia in the absence of concomitant insulin and/or secretagogue therapy. Background therapies might need adjustment to prevent hypoglycemia.

SGLT2 inhibitors should be held in the setting of concomitant dehydrating illness as part of “sick day” management. Patients should be educated on “sick day” management.

These agents have been associated with diabetic ketoacidosis (incidence 0.1%). Patients might present with normal or only modestly elevated blood glucose level (< 14 mmol/L). Rarely, SGLT2 inhibitors might be associated with normal anion gap acidosis (best detected with measurement of serum ketones). Nonspecific symptoms associated with diabetic ketoacidosis include dyspnea, nausea/vomiting, abdominal pain, confusion, anorexia, excessive thirst, and lethargy.

Exercise caution when combining SGLT2 inhibitors, ARNIs, and diuretics because of their concomitant effects to promote diuresis.

For more information, please go to Heart FailureTransthyretin-Related Amyloidosis, and Risk Factors for Coronary Artery Disease.

For more Clinical Practice Guidelines, please go to Guidelines.