Review article: Biomedical intelligence | Published 14 November 2024 | doi:https://doi.org/10.57187/s.

4186
Cite this as: Swiss Med Wkly. 2024;154:4186

Cardiac amyloidosis
Natallia Laptsevaab, Dominik C. Benzabc, Rahel Schwotzerad, Andreas J. Flammerab
a
Amyloidosis Network Zurich, University Hospital Zurich, Zurich, Switzerland
b
University Heart Center, University Hospital Zurich, Zurich, Switzerland
c
Cardiac Imaging, Department of Nuclear Medicine, University Hospital of Zurich, Zurich, Switzerland
d
Hematology and Oncology, University Hospital Zurich, Zurich, Switzerland

AL amyloidosis can occur in any form of B-cell monoclon-

Summary al dyscrasia, typically in plasma cell dyscrasia [3]. Instead
Cardiac amyloidosis is a disease characterised by the ac- of producing normal immunoglobulins, plasma cell or ma-
cumulation of amyloid protein in the heart tissue. There ture B-cell clones produce pathological components (light
are several types of amyloidosis, but the most common chains of monoclonal immunoglobulin), which can aggre-
types affecting the heart are ATTR amyloidosis (caused gate to form amyloid fibrils.
by transthyretin protein) and AL amyloidosis (caused by The liver is the main organ producing transthyretin pre-
abnormal immunoglobulin light chains). Cardiac amyloido- cursor proteins in ATTR amyloidosis. Transthyretin is a
sis causes typical signs and symptoms of heart failure. Di- transport protein for thyroid hormones and retinol.
agnosis involves a combination of imaging tests such as Transthyretin is a tetramer consisting of four monomers.
echocardiography and cardiac magnetic resonance imag- Normally, the tetramers dissociate to monomers and ag-
ing, as well as nuclear imaging scans and tissue biopsies gregate back again [4]. With age (wild-type ATTR [5]), the
to confirm the presence of amyloid deposits in the heart. progressive dissociation of tetramers into monomers re-
Treatment of cardiac amyloidosis depends on the type and sults in the accumulation of monomers in blood and ag-
severity of the disease and includes medications to man- gregation into amyloid fibrils. In rare cases, a mutation in
age symptoms as well as treatments targeting the under- the TTR gene may cause the liver to produce a pathological
lying cause of amyloidosis. Importantly, cardiac amyloido- transthyretin form (variant ATTR – hereditary ATTR-amy-
sis is a serious condition requiring specialised care from a loidosis [4].
multidisciplinary team including cardiologists and haema-
Damage to the organs arises, on the one hand, from de-
tologists as well as other specialists familiar with the man-
position of fibrils into the tissue and, on the other hand,
agement of this rare disease. This is crucial, as early diag-
through direct cytotoxic effects of circulating fibrils and
nosis and treatment are important for improving outcomes.
precursor fibrils (proteotoxicity) [6]. Further, fibrils exhibit
organotropy, tending to deposit in the heart, ligaments and
Introduction nerves in case of ATTRv, while AL amyloid deposits main-
Amyloidosis is a storage disorder occurring when extra- ly into the heart, kidney, gastrointestinal tract and nervous
cellular deposited amyloid leads to dysfunction of various system.
organs. Amyloid is formed in the presence of a protein-
folding disease. Currently, more than 30 different precur- Prognosis
sor proteins are known; however, the two most common
Prognosis of untreated AL amyloidosis is extremely poor,
forms are AL (light chain) and ATTR (transthyretin) amy-
particularly if the heart is affected (mean survival is 6–15
loidosis.
months and 10-year survival rate is below 5%) [3]. The
Despite the heterogeneity of the precursor proteins, the ul- more the heart is affected, the worse the prognosis [7];
trastructural morphology and histochemical properties of however, the prognosis of AL amyloidosis has substantial-
amyloid fibrils are remarkably similar. They share a com- ly improved with new treatment options in recent years [8,
mon core structure of antiparallel β-strands perpendicular 9].
to the long axis of the fibril [1]. This extremely abnor-
The prognosis of wtATTR amyloidosis is generally better
mal, highly ordered conformation underlies the character-
Prof. Dr. Andreas Flammer, than in AL amyloidosis. Several scores predict survival. In
istic properties of amyloid fibrils, including their relative
FESC, FHFA the most commonly used Gillmore score, prognosis main-
Head Heart Failure and stability and resistance to proteolysis, as well as their abili-
ly depends on NT-proBNP values and estimated GFR [10],
Transplantation, Co-Head ty to bind molecules of Congo red dye, resulting in pathog-
with the best prognosis observed when NT-proBNP is be-
Amyloidosis-Network nomonic apple-green birefringence when viewed under
Zurich low 3000 ng/l and estimated GFR is higher than 45 ml/min.
cross-polarised light [2]. Despite the histological similarity
Cardiology
University Hospital of of the amyloid itself, the mechanisms leading to the forma-
Zurich tion of the precursor proteins are completely different, and Prevalence
Raemistrasse 100 thus the pathophysiology of the disease and, of course, the While the incidence and prevalence of AL amyloidosis re-
CH-8091 Zurich
options for causal therapy are completely different. main stable (approximately 1–2 cases per 100,000 sub-
andreas.flammer[at]usz.ch

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Review article: Biomedical intelligence Swiss Med Wkly. 2024;154:4186

jects [11], the incidence and prevalence of ATTR amyloi- up to 83% of patients [17]. While low voltage in the limb
dosis have been increasing over the past few years [12] leads has low sensitivity for ATTR amyloidosis, an abnor-
and may be around 4–17 cases per 100,000 [12, 13]. This mal voltage-to-mass ratio occurs in at least 70% of cardiac
is mainly due to the ageing population, greater awareness amyloidosis [18]. In addition, cardiac amyloidosis is typi-
and better diagnostic tools, particularly scintigraphy. In- cally associated with conduction disease [19].
terestingly, ATTR cardiac amyloidosis is strongly associ-
ated with aortic stenosis (15%) [5] – approximately 16% Diagnostic work-up
of patients in whom transfemoral aortic valve implantation
(TAVI) was performed for severe aortic stenosis showed The presence of typical signs and symptoms of cardiac
concomitant ATTR cardiac amyloidosis [14]. In patients amyloidosis should prompt further testing by echocardiog-
with heart failure and preserved ejection fraction (HFpEF), raphy. Inherently, left ventricular wall thickness represents
ATTR cardiac amyloidosis can be found in as many as the diagnostic hallmark of cardiac amyloidosis [20]. The
13% of the cases [15]. Furthermore, approximately 25% of minimal threshold to screen for cardiac amyloidosis has re-
patients aged over 80 years who died were found to have cently been lowered to 12 mm by a European consensus
transthyretin deposits in the heart [16]. statement [20]. Characteristic echocardiographic findings
of cardiac amyloidosis include pleural or pericardial effu-
sion; thickening of the right ventricle, valves or interatri-
Clinical presentation al septum; a low stroke volume; diastolic dysfunction; and
In cardiac amyloidosis, signs and symptoms of heart fail- a paradoxical low-flow low-gradient aortic stenosis (figure
ure are often the first manifestation, particularly due to 1) [21]. A reduced longitudinal global strain with apical
volume overload. However, a large subset of patients pre- sparing is another characteristic feature, which may be sen-
sent with thoracic complaints such as angina pectoris or or- sitive but has limited specificity [22]. If echocardiography
thostasis and syncope (for typical signs and symptoms, see has a poor acoustic window or echocardiographic findings
table 1). are not suggestive of cardiac amyloidosis, cardiac mag-
Interestingly, patients with ATTR amyloidosis may already netic resonance imaging (CMR) may distinguish structural
be complaining about orthopaedic manifestations 5–15 or functional abnormalities better. Typical findings include
years before cardiac amyloidosis becomes symptomatic – increased left and right ventricular mass (or at least wall
particularly carpal tunnel syndrome, spinal canal stenosis thickness), abnormal gadolinium kinetics, diffuse trans-
and biceps tendon rupture. These findings are generally at- mural or subendocardial late gadolinium enhancement, in-
tributed to amyloidosis only after cardiac amyloidosis is creased T1 mapping or increased extracellular volume,
diagnosed [16]. which has the highest specificity above 40% (figure 1) [23,
24]. Even though CMR may be highly suggestive, it is not
Cardiac amyloidosis is associated with ECG abnormalities.
diagnostic of cardiac amyloidosis.
A typical sign is the pseudo-infarction pattern, found in

Table 1:
Typical findings in amyloidosis.
Cardiac signs and symptoms Shortness of breath (hypervolaemia)
Oedema – Volume retention
Thoracic pain (microvascular angina, elevated filling pressures)
Orthostatic dysregulation, orthostatic hypotension
Syncope
Fatigue
Palpitations – Arrhythmias
Thromboembolism – Stroke
Non-cardiac signs and symptoms Periorbital purpura (AL amyloidosis)
Macroglossia (AL amyloidosis)
Skin bruising – periorbital ecchymosis (AL amyloidosis)
Bilateral carpal tunnel syndrome
Biceps tendon rupture
Lumbar spinal stenosis
Sensory and motor peripheral neuropathy (vATTR)
Weakness
GI symptoms (nausea, diarrhoea, weight loss) – vATTR and AL
Sexual dysfunction
Vitreous opacification, glaucoma (vATTR)
ECG findings Pseudo Q waves
Atrial fibrillation
AV conduction disease
Widened QRS complex
Ventricular premature beats
Low voltage (AL)
Laboratory findings Elevated troponin T and NT-proBNP
Impaired kidney function (AL or cardiorenal in ATTR)
Proteinuria (AL)

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Review article: Biomedical intelligence Swiss Med Wkly. 2024;154:4186

When signs and symptoms, ECG and echocardiography Therefore, and as outlined in the diagnostic algorithm of
(or CMR) are suggestive of cardiac amyloidosis, further the Swiss Amyloidosis Network [27], monoclonal gam-
testing is indicated to (a) diagnose cardiac amyloidosis and mopathy needs to be excluded prior to referral to cardiac
(b) determine the subtype of cardiac amyloidosis. Until re- scintigraphy. This includes quantification of serum free
cently, cardiac amyloidosis was only diagnosed by a pos- light chains as well as serum and urine immunofixation.
itive biopsy, but accumulating literature supports the no- In an isolated free light chain abnormality (i.e. normal im-
tion that cardiac scintigraphy with bone-avid tracers (DPD, munofixation), abnormal kappa/lambda ratio may be ex-
HMDP or PYP) can non-invasively diagnose the disease plained by kidney dysfunction, and eGFR-adjusted ratios
[20]. However, certain limitations need to be considered: are used without affecting the specificity of the test [28].
– When positive, cardiac scintigraphy (which is a planar If monoclonal gammopathy is absent (figure 2), patients
2D scan) always needs to be complemented by single- should be referred to nuclear medicine.
photon emission computed tomography (SPECT) to When cardiac scintigraphy/SPECT with bone-avid tracers
rule out misinterpretation of blood pool activity [25]. is positive (i.e. grade 2 or 3), the patient can be diagnosed
– Cardiac scintigraphy with bone-avid radiotracers has a with cardiac ATTR amyloidosis without biopsy. By ad-
sensitivity over 99% for diagnosing cardiac ATTR amy- hering to this diagnostic algorithm, the diagnostic perfor-
loid deposits in cardiac biopsy. The low number of mance can be summarised as following:
false-negative findings is mainly due to rare hereditary 1. After exclusion of monoclonal gammopathy, cardiac
ATTR forms (i.e. Val30Met and Phe64Leu) [26]. scintigraphy/SPECT with bone-avid tracers has a specifici-
– The specificity of cardiac scintigraphy with bone-avid ty of 100% for diagnosing cardiac amyloidosis [26].
radiotracers is 68% because cardiac scintigraphy de- 2. The sensitivity of the algorithm is 74% for two reasons:
tects other non-ATTR forms of cardiac amyloidosis
– About 20% of these elderly patients suffer from con-
(e.g. cardiac AL amyloidosis). However, the sensitivity
comitant monoclonal gammopathy of unknown signifi-
for diagnosing these non-ATTR forms is much lower
cance (MGUS). In these patients, endomyocardial or
than for cardiac ATTR amyloidosis. For example, 61%
any other organ biopsy is indicated to differentiate AT-
of patients with cardiac AL amyloidosis have grade 0
TR from AL amyloidosis.
and only 10% have grade 2 or 3 in cardiac DPD scintig-
raphy. – Some false-negative cases are due to grade 0 or grade 1
of hereditary or early wild-type forms of ATTR amyloi-

Figure 1: A 56-year-old male with cardiac AL (light chain) amyloidosis. Echocardiography reveals mild asymmetric left ventricular (LV) hyper-
trophy with septal wall thickness of 14 mm (panel A, double-headed arrow) as well as thickening of the right ventricle (RV) and mitral valve
(panel B, arrows). There is reduced global longitudinal strain of –14.3% and relative apical sparing (panel C). Cardiac magnetic resonance
imaging reveals diffuse, predominantly subendocardial late gadolinium enhancement (panel D, arrow). Native T1 times were elevated in the
septum, measuring 1300 ms (panel E).

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Review article: Biomedical intelligence Swiss Med Wkly. 2024;154:4186

dosis [26]. This highlights the fact that high clinical sus- like 18F-florbetapir or 124I-evuzamitide have evolved to di-
picion of cardiac amyloidosis should always trigger fur- agnose cardiac AL amyloidosis non-invasively [32] and
ther testing with CMR or cardiac biopsy, even if cardiac quantify cardiac amyloid burden. In the near future, this
scintigraphy is negative. may hold clinical implications for monitoring treatment re-
If monoclonal gammopathy is present (figure 2), patients sponse [33].
should be referred to haematology for further testing in-
cluding CMR to evaluate cardiac involvement. In case of Treatment
plasma cell or mature B-cell dyscrasia, a tissue biopsy
must be carried out, usually of the most affected organ Symptomatic treatment of cardiac amyloidosis
[29]. If cardiac amyloidosis is suspected, a diagnosis is
High left ventricular filling pressure due to severe diastolic
commonly made with endomyocardial biopsy. However, a
dysfunction is the main clinical problem of patients with
biopsy of another organ, together with typical findings on
cardiac amyloidosis. Therefore, diuretic treatment, togeth-
echocardiography or CMR is valid for the diagnosis of car-
er with patient education to reduce fluid intake, remain the
diac amyloidosis [29].
mainstay of treatment. Diuretic treatment is challenging
Patients with plasma cell dyscrasia due to MGUS pose a due to over-proportional blood pressure decline with an al-
particular diagnostic challenge, as this condition is com- tered pressure/volume relationship.
mon in elderly patients with ATTR cardiac amyloidosis,
Patients with cardiac amyloidosis mainly present with HF-
and is significantly higher than in the general population
pEF. In these patients, traditional heart failure treatment
[30, 31].
with renin-angiotensin-aldosterone inhibition is not estab-
Tissue biopsies are evaluated for the presence of amyloid. lished. A recent large retrospective analysis in more than
Typing is generally done using immunohistochemical 2000 ATTR cardiac amyloidosis patients did not show ben-
staining; however, this technique is challenging and prone efit of ACE inhibitors or angiotensin-receptor blockers on
to errors. In certain cases, the biopsy needs to be assessed outcome, but a high rate of withdrawal due to side effects
by a specialised centre to ascertain the prognosis. Mass [34]. Beta-blockers have been used in cardiac amyloidosis
spectrometry (MS) proteomic analysis, the gold standard, patients; however, low heart rates should be avoided be-
can only be performed at very few centres worldwide. MS cause cardiac output is solely dependent on heart rate given
directly identifies the protein subunit in the deposit and the that stroke volume is fixed in cardiac amyloidosis. In the
accompanying universal amyloid proteins. MS can detect later analysis, beta-blocker therapy showed benefit in pa-
unusual or novel types and its sensitivity and specificity tients with cardiac amyloidosis and an ejection fraction be-
are close to 100% [31]. low 40% (HFrEF) [34]; however, the withdrawal rate due
Currently, cardiac AL amyloidosis cannot be diagnosed to intolerance remains high. Mineralocorticoid receptor an-
non-invasively, so many patients undergo endomyocardial tagonists, however, showed a better tolerability and lower
biopsy [29]. When AL amyloidosis was detected in an ex- mortality and morbidity in these ATTR patients [34].
tracardiac biopsy and echocardiography or CMR are sug- SGLT-2 inhibitors are the mainstay of heart failure treat-
gestive of cardiac amyloidosis, AL cardiomyopathy may ment irrespective of ejection fraction. There are no signs
be diagnosed. More recently, in clinical trials, amyloid- of harm with SGLT-2 inhibitors in cardiac amyloidosis pa-
binding positron emission tomography (PET) radiotracers

Figure 2: Diagnostic algorithm for the diagnosis of cardiac amyloidosis.

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Review article: Biomedical intelligence Swiss Med Wkly. 2024;154:4186

tients, in AL and ATTR alike [35]. However, as well as tachycardias (class IIA, C recommendation) [43]. Certain-
with MRAs more data on outcomes are needed [36, 37]. ly, the decision concerning ICD implantation should be
Very few data are available for patients with AL cardiac made in an amyloidosis centre after in-depth discussion
amyloidosis. In these patients, the abovementioned drugs with the team and the patient.
are usually not tolerated and may induce severe sympto- Toxicity of amyloid fibrils may lead to sinus bradycardia
matic orthostasis. up to sinus arrest and amyloid deposition may delay im-
pulse propagation within the conduction system [41]. Over
Prevention and treatment of arrhythmias time, about 10% of cardiac amyloidosis patients eventually
require a pacemaker. The presence of a first-degree AV
Arrhythmias are very common in cardiac amyloidosis. The
block, wide QRS complex (over 120 ms) and atrial fibrilla-
most common arrhythmia in cardiac amyloidosis is, by far,
tion indicate the highest risk for future pacemaker implan-
atrial fibrillation. Almost all patients develop atrial fib-
tation [44], highlighting the need for regular ECG monitor-
rillation over time, due to elevated filling pressures and
ing.
structural changes in the left atrium. Therefore, regular
screening for atrial fibrillation is important (at 6-month in-
tervals). Stroke risk in cardiac amyloidosis is very high, Disease-modifying treatments
particularly in AL cardiac amyloidosis [19]. This is why The treatment of AL cardiac amyloidosis is mainly in the
oral anticoagulation is mandatory if atrial fibrillation is domain of haemato-oncology, and it varies according to
present. Even in sinus rhythm, the risk of stroke is in- the underlying disease, renal and neurological parameters,
creased – this may be due to elevated left atrial filling and cardiac involvement. In recent years, treatment options
pressure and reduced atrial contraction [19]. Therefore, have increased substantially, and life expectancy increased.
many groups initiate oral anticoagulation even in the ab- Treatment of AL is a huge topic in itself, but not a focus
sence of atrial fibrillation. There are no data on atrial ap- of this review. Notably, AL patients should be treated in an
pendage closure and very limited data on atrial fibrillation amyloidosis centre with an opportunity for an interdiscipli-
ablation in amyloidosis. One study showed a recurrence nary approach [45].
rate of almost 90% in the latter [38]. Therefore, we do
For ATTR cardiac amyloidosis, the only causal treatment
not recommend these interventions in cardiac amyloidosis.
currently approved is the tetramer stabiliser tafamidis. It
Rhythm control should be attempted with electroconver-
prevents dissociation of the transthyretin tetramer to the
sion and amiodarone; however, the success rate is not very
four monomers, thereby preventing the build-up of amy-
high. Beta-blocker therapy or sometimes amiodarone can
loid oligomers and fibrils. Tafamidis was initially devel-
be used for rate control; however, a lenient strategy should
oped for the treatment of familial amyloid polyneuropathy
be adopted, due to the fixed stroke volume [38]. Digoxin
and has been used in this indication for more than 10 years
should be used, if at all, only under very careful monitoring
(approved in the EU but not in Switzerland). The “AT-
[39]. Finally, as in any case of atrial fibrillation refractory
TR-act study” [46] proved the efficacy of tafamidis for the
to medical therapy, atrioventricular nodal ablation and a
treatment of cardiac amyloidosis. Mortality and heart fail-
permanent pacemaker implant can be considered [40].
ure hospitalisation were significantly lowered compared to
Scarring, fibrosis and amyloid itself may have proarrhyth- placebo; however, this benefit seems to be achieved after
mogenic properties leading to the emergence of tach- 18 months only. The effect on quality of life and exer-
yarrhythmias [41]. Although sudden cardiac death (SCD) cise capacity was seen much faster. Currently, tafamidis
is more common in cardiac amyloidosis (particularly AL 61 mg/d is approved for the treatment of cardiac amyloi-
cardiac amyloidosis) than in other cardiomyopathies and dosis in Switzerland (for limitations, see table 2). Recent-
studies show a high number of appropriate (and inappro- ly, the effect of tetramer stabilisation on outcome has been
priate) shocks, no study has so far convincingly demon- confirmed with acoramidis, a tetramer stabiliser similar to
strated a mortality benefit with ICD in patients with car- tafamidis [47].
diac amyloidosis [42]. Nevertheless, the 2022 ESC
Importantly, drug development in cardiac amyloidosis is
Guidelines for the management of patients with ventricular
very dynamic and several new compounds show promising
arrhythmias advocated for ICD implantation in patients
results for the treatment of cardiac amyloidosis. RNA ther-
who have haemodynamically not-tolerated ventricular
apeutics (siRNA and antisense oligonucleotides) can sup-

Table 2:
Limitations from the “Spezialitätenliste” for the treatment of cardiac amyloidosis in Switzerland with tafamidis 61 mg/d. The drug is only reimbursed by the health insurance when
all of the following are present:
Established diagnosis with typical imaging findings along with exclusion of AL amyloidosis and a positive Tc scintigraphy (Perugini 2–3) or histological proof of ATTR
NYHA class I or II
At least one prior hospitalisation for heart failure and/or an episode of a symptomatic documented heart failure
NT-proBNP > 600 ng/l
Able to walk more than 100 m in a 6-minute walk test
Glomerular filtration rate > 25 ml/min/1.73 m2
Life expectancy of at least 2 years
No prior liver or heart transplantation, no “mechanical assist devices”
Must not be combined with other specific drugs for the treatment of TTR amyloidosis (e.g. patisiran, inotersen)
Cardiology centre, included in the list of the Swiss Federal Office of Public Health
NYHA: New York Heart Association.

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Review article: Biomedical intelligence Swiss Med Wkly. 2024;154:4186

press the production of TTR in the liver effectively, thus – There are two main types of amyloid proteins causing
eliminating the protein responsible for TTR amyloidosis. cardiac amyloidosis, with the most common types be-
For hereditary ATTR amyloidosis, three substances are al- ing ATTR and AL amyloidosis.
ready on the market for the treatment of amyloid polyneu- – Symptoms of cardiac amyloidosis vary, but mostly in-
ropathy. Patisiran and vutisiran are small interfering RNAs clude unexplained heart failure symptoms in a patient
(si-RNA) binding to transthyretin messenger RNA (mR- with a thickened septum on echocardiography. Other
NA) to mediate its premature degradation, thereby inhibit- red flags include hypotension in a previously hyperten-
ing its translation into transthyretin protein. Similarly, the sive patient, syncope, unexplained stroke, bilateral
antisense oligonucleotides inotersen and eplontersen inhib- carpal tunnel syndrome, ECG abnormalities (pseudo-Q
it the production of transthyretin. waves) and others.
The Apollo-A (patisiran) [48], Helios-A (vutisiran) [49] – Diagnosis is made by typical imaging findings with
and Neuro-TTR (inotersen) [50], NEURO-TTRansform echocardiography or CMR, together with a positive
(eplontersen) [51] studies showed that the substances technetium scintigraphy in the absence of plasma cell
slowed or even halted the progression of neuropathy in dyscrasia (ATTR) or via tissue biopsy (AL or ATTR).
these patients. The efficacy of these substances in cardiac – The treatment goals for cardiac amyloidosis are to man-
amyloidosis patients with wild-type and hereditaryamyloi- age symptoms and to give medication targeting the un-
dosis is promising. In the recently published Apollo-B tri- derlying cause of amyloidosis.
al, administration of patisiran over 12 months resulted in
– Management of cardiac amyloidosis requires a multi-
preserved functional capacity in ATTR cardiac amyloido-
disciplinary approach, involving cardiologists, haema-
sis [52]. Very recently, the Helios-B study demonstrated
tologists, nephrologists and other specialists. Close
significant reduction of death and cardiovascular events
monitoring and coordination of care are essential to en-
with vutrisiran in patients with ATTR-CM [53]. Of note,
sure high-quality treatment.
RNA therapeutics for hereditary amyloidosis currently can
only be prescribed in one of the amyloidosis centres at Acknowledgments
the university hospitals of Lausanne (CHUV) or Zurich Author contributions: NL, DB, RS and AJF contributed substantially
(USZ). to the conception and design of the work and drafted the work or re-
viewed it critically for important intellectual content. All authors ap-
Furthermore, with CRISPR-Cas9, gene silencing has been proved the final version. All authors are accountable for the work
achieved in patients with hereditary amyloidosis and first- done.
in-man data look very promising. This could be one of
the first gene therapies applied to humans [54]. Recently, Potential competing interests
Fontana et al. described anti-ATTR antibodies in patients NL declares fees from Alnylam and Pfizer. DB received research fund-
ing from the Swiss National Science Foundation and the Swiss Heart
who had recovered from ATTR amyloidosis, highlighting
Foundation. He reports consulting fees from Pfizer and AstraZeneca,
the possibility for reversibility [55]. Further, an exciting other payments from Pfizer, Amgen and Philips Research and roles
phase I study proved the concept that amyloid can be within ASNC (Leadership Development Program, Health Policy Com-
cleared from the tissue via an antibody-mediated phagocy- mittee), EACVI (HIT Ambassador for Echocardiography in Switzer-
totic inflammatory reaction [56]. After infusion of the anti- land) and ESC (ESC Board Committee for Young Cardiovascular Pro-
body, cardiac tracer update on scintigraphy and extracellu- fessionals). University Hospital Zurich holds a research agreement
lar volume on cardiac MRI were reduced after 12 months. with GE Healthcare. RS received financial support from Alnylam,
Pfizer, SOBI, AstraZeneca and Janssen related to this article and finan-
An ongoing phase 3 trial is evaluating this promising new
cial support from Takeda, BMS, Amgen not related to this article. AJF
treatment option. declares fees from Alnylam, Pfizer and AstraZeneca related to this arti-
cle and fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim,
Conclusion Bristol Myers Squibb, Fresenius, Imedos Systems, Medtronic, MSD,
Mundipharma, Novartis, Pierre Fabre, Pfizer, Roche, Schwabe Phar-
Overall, amyloidosis has gained a lot of attention in the last ma, Vifor and Zoll not related to this article.
couple of years. This is mainly based on much better diag-
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