Wild type transthyretin cardiac amyloidosis in a young individual: A case report.

Senile systemic amyloidosis, a disease of elderly is caused by amyloid deposition of wild-type transthyretin. The symptoms often overlap with other heart diseases. Hence it is either misdiagnosed or considered as a normal aging process in majority of cases.

We present a young patient of wild-type transthyretin amyloidosis, contradicting its only senile presence. The 34-year-old man presented with dyspnoea on exertion. He was suffering from hypertension for consecutive 3 years.

Echocardiography demonstrated left ventricular hypertrophy with reduced global longitudinal strain and apical sparing. Congo red staining and immuno-histochemical staining of the abdominal fat biopsy confirmed transthyretin amyloid deposition. Genetic analysis revealed absence of any mutant variant/s of transthyretin gene, confirming wild-type transthyretin amyloidosis.

A combination of amlodipine 5 mg, telmisartan 40 mg, and chlorthalidone 12.5 mg once daily was given to control the blood pressure of the patient.

Blood pressure was controlled but he continued to have exertional dyspnoea. The patient expired in December 2019.

A systematic diagnosis for wild type transthyretin amyloid cardiomyopathy (ATTR-CM) shall be considered in young cardiac patients suffering from cardiac distress with unknown etiology.

    Senile systemic amyloidosis
    DIAGNOSIS

, a disease of

    elderly
    AGE

 is caused by

    amyloid deposition of wild-type transthyretin
    MICROSCOPIC

. The symptoms often

    overlap with other heart diseases
    SYMPTOMS

. Hence it is either

    misdiagnosed
    NEG_FINDINGS

 or considered as a normal aging process in majority of cases.

We present a

    young
    AGE

 patient of

    wild-type transthyretin amyloidosis
    DIAGNOSIS

, contradicting its only senile presence. The

    34-year-old
    AGE

    man
    GENDER

 presented with

    dyspnoea on exertion
    SYMPTOMS

.

    He
    GENDER

 was suffering from

    hypertension for consecutive 3 years
    SYMPTOMS

.

    Echocardiography
    PARACLINICAL

 demonstrated

    left ventricular hypertrophy with reduced global longitudinal strain and apical sparing
    SYMPTOMS

.

    Congo red staining
    PARACLINICAL

 and

    immuno-histochemical staining of the abdominal fat biopsy
    PARACLINICAL

 confirmed

    transthyretin amyloid deposition
    MICROSCOPIC

.

    Genetic analysis
    PARACLINICAL

 revealed

    absence of any mutant variant/s of transthyretin gene
    NEG_FINDINGS

, confirming

    wild-type transthyretin amyloidosis
    DIAGNOSIS

.

A

    combination of amlodipine 5 mg, telmisartan 40 mg, and chlorthalidone 12.5 mg once daily
    MEDICATION

 was given to control the blood pressure of the patient.

    Blood pressure was controlled
    SYMPTOMS

 but

    he
    GENDER

 continued to have

    exertional dyspnoea
    SYMPTOMS

. The patient

    expired
    SYMPTOMS

 in December 2019.

A systematic diagnosis for

    wild type transthyretin amyloid cardiomyopathy (ATTR-CM)
    DIAGNOSIS

 shall be considered in

    young cardiac
    AGE

 patients suffering from

    cardiac distress with unknown etiology
    SYMPTOMS

.


Multi-system neurological disorder associated with a CRYAB variant.

We report a multiplex family with extended multisystem neurological phenotype associated with a CRYAB variant. Two affected siblings were evaluated with whole exome sequencing, muscle biopsy, laser microdissection, and mass spectrometry-based proteomic analysis. Both patients and their mother manifested a combination of early-onset cataracts, cardiomyopathy, cerebellar ataxia, optic atrophy, cognitive impairment, and myopathy. Whole exome sequencing identified a heterozygous c.458C>T variant mapped to the C-terminal extension domain of the Alpha-crystallin B chain, disrupting its function as a molecular chaperone and its ability to suppress protein aggregation. In accordance with the molecular findings, muscle biopsies revealed subsarcolemmal deposits that appeared dark with H&E and trichrome staining were negative for the other routine histochemical staining and for amyloid with the Congo-red stain. Electron microscopy demonstrated that the deposits were composed of numerous parallel fibrils. Laser microdissection and mass spectrometry-based proteomic analysis revealed that the inclusions are almost exclusively composed of crystallized chaperones/heat shock proteins. Moreover, a structural model suggests that Ser153 could be involved in monomer stabilization, dimer association, and possible binding of partner proteins. We propose that our report potentially expands the complex phenotypic spectrum of alpha B-crystallinopathies with possible effect of a CRYAB variant on the central nervous system.

We report a

    multiplex family with extended multisystem neurological phenotype
    FAMILY

 associated with a

    CRYAB variant
    GENETICS

. Two affected siblings were evaluated with

    whole exome sequencing
    PARACLINICAL

,

    muscle biopsy
    PARACLINICAL

,

    laser microdissection
    PARACLINICAL

, and

    mass spectrometry-based proteomic analysis
    PARACLINICAL

. Both patients and their

    mother
    GENDER

 manifested a combination of

    early-onset cataracts
    SYMPTOMS

,

    cardiomyopathy
    SYMPTOMS

,

    cerebellar ataxia
    SYMPTOMS

,

    optic atrophy
    SYMPTOMS

,

    cognitive impairment
    SYMPTOMS

, and

    myopathy
    SYMPTOMS

.

    Whole exome sequencing
    PARACLINICAL

 identified a

    heterozygous c.458C>T variant mapped to the C-terminal extension domain of the Alpha-crystallin B chain, disrupting its function as a molecular chaperone and its ability to suppress protein aggregation
    GENETICS

. In accordance with the molecular findings,

    muscle biopsies
    PARACLINICAL

 revealed

    subsarcolemmal deposits that appeared dark
    MICROSCOPIC

 with H&E and

    trichrome staining were negative for the other routine histochemical staining and for amyloid
    NEG_FINDINGS

 with the

    Congo-red stain
    PARACLINICAL

.

    Electron microscopy
    PARACLINICAL

 demonstrated that the

    deposits were composed of numerous parallel fibrils
    MICROSCOPIC

.

    Laser microdissection and mass spectrometry-based proteomic analysis
    PARACLINICAL

 revealed that

    the inclusions are almost exclusively composed of crystallized chaperones/heat shock proteins
    MICROSCOPIC

. Moreover, a structural model suggests that

    Ser153
    GENETICS

 could be involved in monomer stabilization, dimer association, and possible binding of partner proteins. We propose that our report potentially expands the complex phenotypic spectrum of

    alpha B-crystallinopathies
    DIAGNOSIS

 with possible effect of a

    CRYAB variant
    GENETICS

 on the

    central nervous system
    SYMPTOMS

.

early-onset cataracts
cardiomyopathy
cerebellar ataxia
optic atrophy
cognitive impairment
myopathy
central nervous system


Exertional chest pain is sometimes more than just coronary atherosclerosis.

A 64-year-old male, with cardiovascular risk factors and previous history of bilateral carpal tunnel syndrome, presented with exertional retrosternal pain. The resting echocardiogram was unremarkable. A stress echocardiogram with dobutamine revealed hypokinesis of the inferior wall, associated with angina, followed by ventricular tachycardia. The coronary angiography revealed slow flow, a dominant right coronary artery with non-obstructive atherosclerosis and a left anterior descending artery with intermediate lesions in mid and distal segments. The invasive functional evaluation, including fractional flow reserve, thermodilution coronary flow reserve and index of microvascular resistance, led to the diagnosis of microvascular angina, treated with calcium channel blockers and transdermal nitrate, giving symptom relief.

Three years later he developed complete atrioventricular block and a dual chamber pacemaker was implanted. Shortly after, the patient developed progressive symmetrical tetraparesis, associated with marked muscle atrophy, hand numbness, orthostatic hypotension and dysphagia. The neurology workup led to the diagnosis of familial amyloidotic polyneuropathy, with the Val30Met mutation in the transthyretin gene. The following year he developed congestive heart failure. The echocardiogram showed moderate concentric left ventricular hypertrophy with preserved ejection fraction. A 99mTc-DPD Scintigraphy showed significant myocardial tracer uptake, leading to a diagnosis of TTR amyloid infiltration.

Patients with exertional angina and microvascular disease should be kept under close surveillance, as they may have systemic disease with cardiac involvement. Carpal tunnel syndrome, in the context of undiagnosed cardiac disease, should trigger suspicion of cardiac amyloidosis.

A

    64-year-old
    AGE

    male
    GENDER

, with

    cardiovascular risk factors
    SYMPTOMS

 and

    previous history of bilateral carpal tunnel syndrome
    FAMILY

, presented with

    exertional retrosternal pain
    SYMPTOMS

. The

    resting echocardiogram was unremarkable
    NEG_FINDINGS

. A

    stress echocardiogram with dobutamine
    PARACLINICAL

 revealed

    hypokinesis of the inferior wall
    SYMPTOMS

, associated with

    angina
    SYMPTOMS

, followed by

    ventricular tachycardia
    SYMPTOMS

. The

    coronary angiography
    PARACLINICAL

 revealed

    slow flow, a dominant right coronary artery with non-obstructive atherosclerosis and a left anterior descending artery with intermediate lesions in mid and distal segments
    SYMPTOMS

. The

    invasive functional evaluation
    PARACLINICAL

, including

    fractional flow reserve, thermodilution coronary flow reserve
    PARACLINICAL

 and

    index of microvascular resistance
    PARACLINICAL

, led to the diagnosis of

    microvascular angina
    DIAGNOSIS

, treated with

    calcium channel blockers and transdermal nitrate
    MEDICATION

, giving

    symptom relief
    SYMPTOMS

.

Three years later

    he
    GENDER

 developed

    complete atrioventricular block
    SYMPTOMS

 and a

    dual chamber pacemaker was implanted
    MEDICATION

. Shortly after, the patient developed

    progressive symmetrical tetraparesis
    SYMPTOMS

, associated with

    marked muscle atrophy
    SYMPTOMS

,

    hand numbness
    SYMPTOMS

,

    orthostatic hypotension
    SYMPTOMS

 and

    dysphagia
    SYMPTOMS

. The

    neurology workup
    PARACLINICAL

 led to the diagnosis of

    familial amyloidotic polyneuropathy
    DIAGNOSIS

, with the

    Val30Met mutation in the transthyretin gene
    GENETICS

. The following year

    he
    GENDER

 developed

    congestive heart failure
    SYMPTOMS

. The

    echocardiogram
    PARACLINICAL

 showed

    moderate concentric left ventricular hypertrophy with preserved ejection fraction
    SYMPTOMS

. A

    99mTc-DPD Scintigraphy
    PARACLINICAL

 showed

    significant myocardial tracer uptake
    SYMPTOMS

, leading to a diagnosis of

    TTR amyloid infiltration
    DIAGNOSIS

.

Patients with

    exertional angina
    SYMPTOMS

 and

    microvascular disease
    DIAGNOSIS

 should be kept under close surveillance, as they may have

    systemic disease
    DIAGNOSIS

 with

    cardiac involvement
    SYMPTOMS

.

    Carpal tunnel syndrome
    DIAGNOSIS

, in the context of

    undiagnosed cardiac disease
    SYMPTOMS

, should trigger suspicion of

    cardiac amyloidosis
    DIAGNOSIS

.

microvascular angina
familial amyloidotic polyneuropathy
TTR amyloid infiltration
microvascular disease
systemic disease
Carpal tunnel syndrome
cardiac amyloidosis


Wild-type transthyretin amyloid cardiomyopathy complicated by spinal canal stenosis, carpal tunnel syndrome, and rotator cuff tears: a case report.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is receiving increasing attention due to the availability of novel treatment options. Carpal tunnel syndrome (CTS) and lumbar spinal canal stenosis are known early symptoms of transthyretin (TTR) amyloidosis preceding the cardiac involvement and are considered as 'Red Flags' for transthyretin amyloid cardiomyopathy (ATTR-CM).

A 67-year-old man with a history of lumbar spinal canal stenosis for the last 10 years, right rotator cuff tears for the last 4 years, and bilateral CTS for the last 1 year was scheduled for orthopaedic surgery for lumbar spinal canal stenosis. Investigations revealed severe left ventricular hypertrophy and hypertroponinaemia, which were suggestive of cardiac amyloidosis. Cardiac magnetic resonance imaging and 99mTc-labelled pyrophosphate scintigraphy demonstrated positive findings for ATTR-CM. Transthyretin deposition was found in both the myocardium and the yellow ligamentum excised during surgery. There was no transthyretin mutation on genetic testing. The final diagnosis was ATTRwt-CM.

Transthyretin deposition in the ligaments or tendons has been observed in a number of patients with CTS, spinal canal stenosis, and rotator cuff tears. These orthopaedic diseases are predictive for the future occurrence of ATTR-CM. In addition, the coexistence of these multiple diseases might strongly predict ATTR-CM. This knowledge needs to be shared with orthopaedicians and cardiologists for the early diagnosis of ATTR-CM.

    Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM)
    DIAGNOSIS

 is receiving increasing attention due to the availability of novel treatment options.

    Carpal tunnel syndrome (CTS)
    SYMPTOMS

 and

    lumbar spinal canal stenosis
    SYMPTOMS

 are known early symptoms of

    transthyretin (TTR) amyloidosis
    DIAGNOSIS

 preceding the

    cardiac involvement
    SYMPTOMS

 and are considered as 'Red Flags' for

    transthyretin amyloid cardiomyopathy (ATTR-CM)
    DIAGNOSIS

.

A

    67-year-old
    AGE

    man
    GENDER

 with a history of

    lumbar spinal canal stenosis for the last 10 years
    SYMPTOMS

,

    right rotator cuff tears for the last 4 years
    SYMPTOMS

, and

    bilateral CTS for the last 1 year
    SYMPTOMS

 was scheduled for

    orthopaedic surgery
    MEDICATION

 for

    lumbar spinal canal stenosis
    DIAGNOSIS

. Investigations revealed

    severe left ventricular hypertrophy
    SYMPTOMS

 and

    hypertroponinaemia
    BIOCHEMICAL

, which were suggestive of

    cardiac amyloidosis
    DIAGNOSIS

.

    Cardiac magnetic resonance imaging
    PARACLINICAL

 and

    99mTc-labelled pyrophosphate scintigraphy
    PARACLINICAL

 demonstrated

    positive findings for ATTR-CM
    SYMPTOMS

.

    Transthyretin deposition was found in both the myocardium and the yellow ligamentum excised
    MICROSCOPIC

 during

    surgery
    MEDICATION

. There was

    no transthyretin mutation on genetic testing
    NEG_FINDINGS

. The final diagnosis was

    ATTRwt-CM
    DIAGNOSIS

.

    Transthyretin deposition in the ligaments or tendons
    MICROSCOPIC

 has been observed in a number of patients with

    CTS
    DIAGNOSIS

,

    spinal canal stenosis
    SYMPTOMS

, and

    rotator cuff tears
    SYMPTOMS

. These orthopaedic diseases are predictive for the future occurrence of

    ATTR-CM
    DIAGNOSIS

. In addition, the coexistence of these

    multiple diseases
    SYMPTOMS

 might strongly predict

    ATTR-CM
    DIAGNOSIS

. This knowledge needs to be shared with

    orthopaedicians
    PARACLINICAL

 and

    cardiologists
    PARACLINICAL

 for the early diagnosis of

    ATTR-CM
    DIAGNOSIS

.


Strange case of biventricular heart failure.

Acute heart failure (HF) is commonly caused by a cardiomyopathy with one or more precipitating factor. Here, a case in which a cardiomyopathy is precipitated by pulmonary embolism (PE). A 77-year-old man is admitted for breathlessness and leg swelling. A mild reduction of left ventricular (LV) ejection fraction is found, with moderately increased LV wall thickness and pulmonary hypertension; clinical examination revealed signs of congestion with bilateral leg swelling, and mild signs of left HF with the absence of pulmonary congestion on chest X-ray. The ECG showed Mobitz I second-degree atrioventricular block. The clinical scenario led us to the diagnosis of infiltrative cardiomyopathy due to cardiac amyloidosis (CA) precipitated by PE. Pulmonary embolism is an overlooked precipitant of HF and can be the first manifestation of an underlying misdiagnosed cardiomyopathy, especially CA. 3,3-Diphosphono-1,2-propanodicarboxylic acid scan is a cornerstone in the diagnosis of Transthyretin amyloidosis (ATTR) cardiac amyloidosis.

    Acute heart failure (HF)
    DIAGNOSIS

 is commonly caused by a

    cardiomyopathy
    DIAGNOSIS

 with one or more precipitating factor. Here, a case in which a

    cardiomyopathy
    DIAGNOSIS

 is precipitated by

    pulmonary embolism (PE)
    SYMPTOMS

. A

    77-year-old
    AGE

    man
    GENDER

 is admitted for

    breathlessness
    SYMPTOMS

 and

    leg swelling
    SYMPTOMS

. A

    mild reduction of left ventricular (LV) ejection fraction
    SYMPTOMS

 is found, with

    moderately increased LV wall thickness
    SYMPTOMS

 and

    pulmonary hypertension
    SYMPTOMS

; clinical examination revealed

    signs of congestion with bilateral leg swelling
    SYMPTOMS

, and

    mild signs of left HF
    SYMPTOMS

 with the

    absence of pulmonary congestion on chest X-ray
    NEG_FINDINGS

. The

    ECG
    PARACLINICAL

 showed

    Mobitz I second-degree atrioventricular block
    SYMPTOMS

. The clinical scenario led us to the diagnosis of

    infiltrative cardiomyopathy due to cardiac amyloidosis (CA)
    DIAGNOSIS

 precipitated by

    PE
    DIAGNOSIS

.

    Pulmonary embolism
    SYMPTOMS

 is an overlooked precipitant of

    HF
    DIAGNOSIS

 and can be the first manifestation of an underlying misdiagnosed

    cardiomyopathy
    DIAGNOSIS

, especially

    CA
    DIAGNOSIS

. 3,3

    -Diphosphono-1,2-propanodicarboxylic acid scan
    PARACLINICAL

 is a cornerstone in the diagnosis of

    Transthyretin amyloidosis (ATTR) cardiac amyloidosis
    DIAGNOSIS

.


A case report of an infiltrative cardiomyopathy in everyday practice: a specific cause that cannot be missed in the elderly.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a commonly misdiagnosed cardiac condition due to low disease awareness and perceived rarity, which frequently results in incorrect management and poor outcomes. Early and prompt diagnosis has become critical with emerging therapies that improve patient survival.

A 68-year-old woman presented to a tertiary care centre with acute decompensated heart failure following recurrent hospitalizations for the same issue over the past several months. Transthoracic echocardiography revealed severe concentric left ventricular hypertrophy with grade III diastolic dysfunction. However, QRS voltage by 12-lead electrocardiogram (ECG) was discordant with the degree of left ventricular hypertrophy seen by echocardiography, and the patient had recurrent non-sustained ventricular tachycardia that necessitated implantable cardioverter-defibrillator implantation a few months prior. After aggressive diuresis, the patient completed cardiac magnetic resonance imaging that raised concern for cardiac amyloidosis. Subsequent serum and urine protein electrophoresis with associated immunofixation were within normal limits. Finally, ATTR-CM was confirmed by technetium-99m pyrophosphate scintigraphy with plans to initiate tafamidis after genetic testing.

Patients >60 years of age with diastolic heart failure phenotypically similar to hypertrophic cardiomyopathy and/or hypertensive heart disease should always be evaluated for ATTR-CM. Features that increase suspicion include discordance between left ventricular wall thickness and ECG voltage, and signs/symptoms of a primary peripheral and autonomic neuropathy. Useful non-invasive diagnostic testing has also made the diagnosis of ATTR-CM inexpensive and possible without the need for an endomyocardial biopsy. Unfortunately, this patient's diagnosis of ATTR-CM came late in her disease course, which delayed the onset of definitive therapy.

    Transthyretin amyloid cardiomyopathy (ATTR-CM)
    DIAGNOSIS

 is a commonly misdiagnosed

    cardiac condition
    DIAGNOSIS

 due to low disease awareness and perceived rarity, which frequently results in incorrect management and poor outcomes. Early and prompt diagnosis has become critical with emerging therapies that improve patient survival.

A

    68-year-old
    AGE

    woman
    GENDER

 presented to a tertiary care centre with

    acute decompensated heart failure
    SYMPTOMS

 following

    recurrent hospitalizations for the same issue over the past several months
    SYMPTOMS

.

    Transthoracic echocardiography
    PARACLINICAL

 revealed

    severe concentric left ventricular hypertrophy
    SYMPTOMS

 with

    grade III diastolic dysfunction
    SYMPTOMS

. However,

    QRS voltage by 12-lead electrocardiogram (ECG) was discordant with the degree of left ventricular hypertrophy
    SYMPTOMS

 seen by

    echocardiography
    PARACLINICAL

, and the patient had

    recurrent non-sustained ventricular tachycardia
    NEG_FINDINGS

 that necessitated

    implantable cardioverter-defibrillator implantation
    MEDICATION

 a few months prior. After

    aggressive diuresis
    MEDICATION

, the patient completed

    cardiac magnetic resonance imaging
    PARACLINICAL

 that raised concern for

    cardiac amyloidosis
    DIAGNOSIS

. Subsequent

    serum and urine protein electrophoresis
    PARACLINICAL

 with associated

    immunofixation were within normal limits
    NEG_FINDINGS

. Finally,

    ATTR-CM
    DIAGNOSIS

 was confirmed by

    technetium-99m pyrophosphate scintigraphy
    PARACLINICAL

 with plans to initiate

    tafamidis
    MEDICATION

 after

    genetic testing
    PARACLINICAL

.

Patients

    >60 years of age
    AGE

 with

    diastolic heart failure phenotypically similar to hypertrophic cardiomyopathy
    SYMPTOMS

 and/or

    hypertensive heart disease
    DIAGNOSIS

 should always be evaluated for

    ATTR-CM
    DIAGNOSIS

. Features that increase suspicion include

    discordance between left ventricular wall thickness and ECG voltage
    SYMPTOMS

, and

    signs/symptoms of a primary peripheral and autonomic neuropathy
    SYMPTOMS

. Useful non-invasive diagnostic testing has also made the diagnosis of

    ATTR-CM
    DIAGNOSIS

 inexpensive and possible

    without the need for an endomyocardial biopsy
    NEG_FINDINGS

. Unfortunately, this patient's diagnosis of

    ATTR-CM
    DIAGNOSIS

 came late in her disease course, which delayed the onset of definitive therapy.


A Cardiac Amyloidosis Presentation: Atrial Mass Versus Thrombus.

Cardiac neoplasms are a rare finding of which a cardiac myxoma is the most commonly encountered. Therefore, a density identified in the left atrium commonly leads to the presumptive diagnosis of an atrial myxoma. However, other pathologies, such as atrial thrombi, can mimic in clinical presentation and appearance to a myxoma. Clinically, these pathologies may lead to obstructive symptoms such as syncope, palpitations, or sudden cardiac death. At present, echocardiography, magnetic resonance imaging, or computed tomography can be used to identify such masses, but fall short of identifying the primary cause. The management of atrial thrombi is not yet fully understood and definite recommendations have not been established. We present a case of an 87-year-old man complaining of syncopal episodes found to be secondary to an incidental intracardiac density resulting from age-related amyloidosis.

    Cardiac neoplasms
    DIAGNOSIS

 are a rare finding of which a

    cardiac myxoma
    DIAGNOSIS

 is the most commonly encountered. Therefore, a

    density identified in the left atrium
    SYMPTOMS

 commonly leads to the presumptive diagnosis of an

    atrial myxoma
    DIAGNOSIS

. However, other pathologies, such as

    atrial thrombi
    SYMPTOMS

, can mimic in clinical presentation and appearance to a

    myxoma
    SYMPTOMS

. Clinically, these pathologies may lead to

    obstructive symptoms
    SYMPTOMS

 such as

    syncope
    SYMPTOMS

,

    palpitations
    SYMPTOMS

, or

    sudden cardiac death
    SYMPTOMS

. At present,

    echocardiography
    PARACLINICAL

,

    magnetic resonance imaging
    PARACLINICAL

, or

    computed tomography
    PARACLINICAL

 can be used to identify such masses, but fall short of identifying the primary cause. The management of

    atrial thrombi
    SYMPTOMS

 is not yet fully understood and definite recommendations have not been established. We present a case of an

    87-year-old
    AGE

    man
    GENDER

 complaining of

    syncopal episodes
    SYMPTOMS

 found to be secondary to an

    incidental intracardiac density
    SYMPTOMS

 resulting from

    age-related amyloidosis
    DIAGNOSIS

.

Cardiac neoplasms
cardiac myxoma
atrial myxoma
age-related amyloidosis

density identified in the left atrium
atrial thrombi
myxoma
obstructive symptoms
syncope
palpitations
sudden cardiac death
atrial thrombi
syncopal episodes
incidental intracardiac density


Sustained Ventricular Tachycardia as a Harbinger of Cardiac Amyloidosis.

BACKGROUND Cardiac amyloidosis is an infiltrative cardiomyopathy caused by the extracellular deposition of insoluble precursor protein amyloid fibrils. These depositions of protein amyloid fibrils are found on the atria and ventricles and can cause a wide array of arrhythmias; however, sustained ventricular arrhythmias are quite uncommon. CASE REPORT A 71-year-old man with a history of hypertension developed a sudden onset of shortness of breath, profuse diaphoresis, lightheadedness, and presyncope. Upon emergency medical services' arrival, an initial electrocardiogram revealed wide complex tachycardia with a heart rate of 220 to 230 beats per min. He was subsequently given, in succession, magnesium, adenosine, and amiodarone with no change in heart rate or rhythm. Due to ongoing symptoms of diaphoresis and the development of dyspnea, he underwent direct current cardioversion and was converted from ventricular tachycardia to atrial fibrillation at controlled rates. A transthoracic echocardiogram and cardiac magnetic resonance imaging showed features suspicious for cardiac amyloidosis. A subsequent 99m technetium pyrophosphate single-photon emission computerized tomography scan revealed a grade 3 visual uptake and a heart-to-contralateral lung ratio of 1.92, consistent with transthyretin amyloidosis. The patient was treated with tafamidis and an implantable cardioverter-defibrillator for secondary prevention of ventricular arrhythmia. CONCLUSIONS This case highlights the need to consider cardiac amyloidosis in the differential diagnoses of patients with persistent ventricular arrhythmia and no prior history of heart disease.

BACKGROUND

    Cardiac amyloidosis
    DIAGNOSIS

 is an

    infiltrative cardiomyopathy
    DIAGNOSIS

 caused by the

    extracellular deposition of insoluble precursor protein amyloid fibrils
    MICROSCOPIC

. These

    depositions of protein amyloid fibrils are found on the atria and ventricles
    MICROSCOPIC

 and can cause a wide array of

    arrhythmias
    SYMPTOMS

; however,

    sustained ventricular arrhythmias
    SYMPTOMS

 are quite uncommon. CASE REPORT A

    71-year-old
    AGE

    man
    GENDER

 with a history of

    hypertension
    SYMPTOMS

 developed a

    sudden onset of shortness of breath
    SYMPTOMS

,

    profuse diaphoresis
    SYMPTOMS

,

    lightheadedness
    SYMPTOMS

, and

    presyncope
    SYMPTOMS

. Upon emergency medical services' arrival, an initial

    electrocardiogram
    PARACLINICAL

 revealed

    wide complex tachycardia with a heart rate of 220 to 230 beats per min
    SYMPTOMS

.

    He
    GENDER

 was subsequently given, in succession,

    magnesium, adenosine, and amiodarone
    MEDICATION

 with

    no change in heart rate or rhythm
    NEG_FINDINGS

. Due to

    ongoing symptoms of diaphoresis
    SYMPTOMS

 and the

    development of dyspnea
    SYMPTOMS

,

    he
    GENDER

 underwent

    direct current cardioversion
    MEDICATION

 and was

    converted from ventricular tachycardia to atrial fibrillation at controlled rates
    SYMPTOMS

. A

    transthoracic echocardiogram
    PARACLINICAL

 and

    cardiac magnetic resonance imaging
    PARACLINICAL

 showed features suspicious for

    cardiac amyloidosis
    DIAGNOSIS

. A subsequent

    99m technetium pyrophosphate single-photon emission computerized tomography scan
    PARACLINICAL

 revealed a

    grade 3 visual uptake and a heart-to-contralateral lung ratio of 1.92
    SYMPTOMS

, consistent with

    transthyretin amyloidosis
    DIAGNOSIS

. The patient was treated with

    tafamidis and an implantable cardioverter-defibrillator
    MEDICATION

 for

    secondary prevention of ventricular arrhythmia
    SYMPTOMS

. CONCLUSIONS This case highlights the need to consider

    cardiac amyloidosis
    DIAGNOSIS

 in the

    differential diagnoses
    PARACLINICAL

 of patients with

    persistent ventricular arrhythmia
    SYMPTOMS

 and

    no prior history of heart disease
    NEG_FINDINGS

.

Cardiac amyloidosis
infiltrative cardiomyopathy
cardiac amyloidosis
transthyretin amyloidosis
cardiac amyloidosis

no change in heart rate or rhythm
no prior history of heart disease


Suspecting Cardiac Amyloidosis in Congestive Heart Failure.

Amyloidosis is a rare multisystem disease due to deposition of abnormal protein fragments, and cardiac amyloidosis is progressive and difficult to diagnose due to its subtle and non-specific symptoms unless the physician maintains a high degree of suspicion. This case report focuses on amyloid deposition in the heart of an 84-year-old woman who presented with symptoms of uncompensated heart failure.

    Amyloidosis
    DIAGNOSIS

 is a

    rare multisystem disease
    DIAGNOSIS

 due to

    deposition of abnormal protein fragments
    MICROSCOPIC

, and

    cardiac amyloidosis
    DIAGNOSIS

 is progressive and difficult to diagnose due to its subtle and

    non-specific symptoms
    NEG_FINDINGS

 unless the physician maintains a high degree of suspicion. This case report focuses on

    amyloid deposition in the heart
    MICROSCOPIC

 of an

    84-year-old
    AGE

    woman
    GENDER

 who presented with

    symptoms of uncompensated heart failure
    SYMPTOMS

.

Amyloidosis
rare multisystem disease
cardiac amyloidosis


Tetraparesis and sensorimotor axonal polyneuropathy due to co-occurrence of Pompe disease and hereditary ATTR amyloidosis.

Hereditary transthyretin amyloidosis with polyneuropathy (hATTRPN) is an autosomal dominant multi-organ disorder manifesting in the third to fifth decade with the key clinical features of distal and painful sensory loss of the lower limbs and autonomic dysregulation. Motor neuropathy and cardiomyopathy evolve in the course of the disease. Pompe disease is an autosomal recessive disease leading to decreased levels of lysosomal enzyme acid α-glucosidase and proximal muscle weakness. We report the clinical features and diagnostic workup in the rare case of a patient with ATTR amyloidosis and late-onset Pompe disease, both genetically confirmed.

We performed a detailed clinical assessment, exome sequencing, and biochemical measurements.

The patient presented with a distal, painful hypaesthesia of both legs, a cardiomyopathy, and a muscle weakness in the form of a girdle-type pattern of the arms and legs at the beginning and a spreading to distal muscle groups in the course of disease.

This study highlights the importance of searching for co-occurrence of rare monogenetic neuromuscular diseases, especially in cases in which all clinical features can be readily explained by a single gene defect.

    Hereditary transthyretin amyloidosis with polyneuropathy (hATTRPN)
    DIAGNOSIS

 is an

    autosomal dominant
    GENETICS

    multi-organ disorder
    DIAGNOSIS

 manifesting in the

    third to fifth decade
    AGE

 with the key clinical features of

    distal and painful sensory loss of the lower limbs
    SYMPTOMS

 and

    autonomic dysregulation
    SYMPTOMS

.

    Motor neuropathy
    SYMPTOMS

 and

    cardiomyopathy
    SYMPTOMS

 evolve in the course of the disease.

    Pompe disease
    DIAGNOSIS

 is an

    autosomal recessive disease
    GENETICS

 leading to

    decreased levels of lysosomal enzyme acid α-glucosidase
    BIOCHEMICAL

 and

    proximal muscle weakness
    SYMPTOMS

. We report the clinical features and diagnostic workup in the rare case of a patient with

    ATTR amyloidosis
    DIAGNOSIS

 and

    late-onset Pompe disease
    DIAGNOSIS

, both genetically confirmed.

We performed a

    detailed clinical assessment
    PARACLINICAL

,

    exome sequencing
    PARACLINICAL

, and

    biochemical measurements
    PARACLINICAL

.

The patient presented with a

    distal, painful hypaesthesia of both legs
    SYMPTOMS

, a

    cardiomyopathy
    DIAGNOSIS

, and a

    muscle weakness in the form of a girdle-type pattern of the arms and legs at the beginning and a spreading to distal muscle groups
    SYMPTOMS

 in the course of disease.

This study highlights the importance of searching for

    co-occurrence of rare monogenetic neuromuscular diseases
    FAMILY

, especially in cases in which all clinical features can be readily explained by a single gene defect.

autosomal dominant
autosomal recessive disease


Cardiac Amyloidosis Detected on Imaging of Patients with Heart Failure.

BACKGROUND Amyloidosis is a multisystem disease caused by deposition of dysfunctional protein-amyloid-in various organs. The heart is commonly involved, especially in primary (AL) and transthyretin (ATTR) amyloidosis. Most patients present with restrictive cardiomyopathy along with other systemic features of amyloid deposition. Diagnosing amyloidosis is cumbersome and based on the patient's clinical condition and findings from electrocardiography, routine laboratory tests, cardiac biomarkers, imaging, and biopsy. Echocardiography (echo) is a widely available diagnostic imaging method that can help raise suspicion of cardiac amyloidosis (CA) if novel parameters of systolic dysfunction are used, which are based on strain measurement complemented with traditional morphologic and hemodynamic traits. A definitive diagnosis of amyloidosis requires biopsy. It is important to differentiate between AL and ATTR amyloidosis because the treatment approaches for them differ. The prognosis for CA is still dismal but can be improved with early diagnosis and institution of treatment. CASE REPORT Our patients presented with advanced heart failure and subtle clinical signs of amyloidosis. AL amyloidosis was diagnosed based on echo findings and confirmed with bone marrow biopsy. In this report, we describe classic nonspecific echo signs followed by novel parameters of systolic dysfunction. CONCLUSIONS Because the symptoms and signs of amyloidosis are nonspecific, the diagnosis requires a high level of clinical suspicion. Severe diastolic heart failure should prompt a further search for subtle signs on echo that indicate possible amyloid deposition disease. Use of systolic strain analysis increases the specificity of echo for diagnosis of amyloidosis. Echo results combined with specific clinical symptoms and results of a hematology workup can be used to diagnose CA when other, less common tests are not available or invasive testing is not desirable.

BACKGROUND

    Amyloidosis
    DIAGNOSIS

 is a

    multisystem disease
    DIAGNOSIS

 caused by

    deposition of dysfunctional protein-amyloid-in various organs
    MICROSCOPIC

. The

    heart
    SYMPTOMS

 is commonly involved, especially in

    primary (AL) and transthyretin (ATTR) amyloidosis
    DIAGNOSIS

. Most patients present with

    restrictive cardiomyopathy
    SYMPTOMS

 along with other

    systemic features of amyloid deposition
    SYMPTOMS

. Diagnosing

    amyloidosis
    DIAGNOSIS

 is cumbersome and based on the patient's clinical condition and findings from

    electrocardiography
    PARACLINICAL

,

    routine laboratory tests
    PARACLINICAL

,

    cardiac biomarkers
    PARACLINICAL

,

    imaging
    PARACLINICAL

, and

    biopsy
    PARACLINICAL

.

    Echocardiography (echo)
    PARACLINICAL

 is a widely available diagnostic imaging method that can help raise suspicion of

    cardiac amyloidosis (CA)
    DIAGNOSIS

 if novel parameters

    of systolic dysfunction
    SYMPTOMS

 are used, which are based on

    strain measurement
    PARACLINICAL

 complemented with

    traditional morphologic and hemodynamic traits
    PARACLINICAL

. A definitive diagnosis of

    amyloidosis
    DIAGNOSIS

 requires

    biopsy
    PARACLINICAL

. It is important to differentiate between

    AL
    DIAGNOSIS

 and

    ATTR amyloidosis
    DIAGNOSIS

 because the treatment approaches for them differ. The prognosis for

    CA
    DIAGNOSIS

 is still dismal but can be improved with early diagnosis and institution of treatment. CASE REPORT Our patients presented with

    advanced heart failure
    SYMPTOMS

 and

    subtle clinical signs of amyloidosis
    SYMPTOMS

.

    AL amyloidosis
    DIAGNOSIS

 was diagnosed based on

    echo findings
    PARACLINICAL

 and confirmed with

    bone marrow biopsy
    PARACLINICAL

. In this report, we describe

    classic nonspecific echo signs
    SYMPTOMS

 followed by

    novel parameters of systolic dysfunction
    SYMPTOMS

. CONCLUSIONS Because the symptoms and signs of

    amyloidosis
    SYMPTOMS

 are nonspecific, the diagnosis requires a high level of clinical suspicion.

    Severe diastolic heart failure
    SYMPTOMS

 should prompt a further search for

    subtle signs on echo
    SYMPTOMS

 that indicate possible

    amyloid deposition disease
    DIAGNOSIS

. Use of

    systolic strain analysis
    PARACLINICAL

 increases the specificity of

    echo
    PARACLINICAL

 for diagnosis of

    amyloidosis
    DIAGNOSIS

.

    Echo results
    PARACLINICAL

 combined with specific clinical symptoms and results of a

    hematology workup
    PARACLINICAL

 can be used to diagnose

    CA
    DIAGNOSIS

 when other, less common tests are not available or

    invasive testing is not desirable
    NEG_FINDINGS

.


A case of cardiac amyloidosis in an elderly Japanese patient with amyloidogenic transthyretin Val122Ile variant.

A 76-year-old Japanese man with a history of stomach cancer and chronic atrial fibrillation was referred to our department with left atrial thrombus. He had a history of gastric amyloidosis diagnosed by a pathological specimen of the stomach; however, further examination for amyloidosis was not performed. The patient displayed clinical signs and symptoms of heart failure and echocardiography showed a thick left ventricular wall. Since cardiac amyloidosis was suspected, the patient underwent cardiac magnetic resonance imaging and 99mTc-pyrophosphate scintigraphy. These results are consistent with transthyretin amyloidosis (ATTR amyloidosis). DNA analysis of transthyretin (TTR) was performed and a heterozygous Val122Ile mutation was identified. Notably, his only son requested the analysis; however, no mutations were noted. ATTR Val122Ile is one of the mutations in TTR that are associated with hereditary amyloidosis, causing severe cardiomyopathy. The prevalence of the ATTR Val122Ile mutation is 3.9% in the African-American population. However, the occurrence of this mutation in Asian populations is very rare. This is the second reported case of the ATTR Val122Ile variant in Japan and the first case tested including familial genes. <Learning objective: Transthyretin amyloidosis (ATTR) Val122Ile variant is rare in Asian people. This is the second case of ATTR Val122Ile variant in Japan and the first case tested including familial genes. This case suggests this mutation is present even in Asian people. It is important to evaluate transthyretin gene mutations even in elderly ATTR cardiac amyloid without apparent family history of amyloidosis. If there is a gene mutation, it is necessary to search for transthyretin mutation within the family members.>.

A

    76-year-old
    AGE

    Japanese
    ETHNICITY

    man
    GENDER

 with a history of

    stomach cancer
    DIAGNOSIS

 and

    chronic atrial fibrillation
    SYMPTOMS

 was referred to our department with

    left atrial thrombus
    SYMPTOMS

.

    He
    GENDER

 had a history of

    gastric amyloidosis
    DIAGNOSIS

 diagnosed by a

    pathological specimen of the stomach
    PARACLINICAL

; however, further examination for

    amyloidosis
    NEG_FINDINGS

    was not performed
    NEG_FINDINGS

. The patient displayed

    clinical signs and symptoms of heart failure
    SYMPTOMS

 and

    echocardiography
    PARACLINICAL

 showed a

    thick left ventricular wall
    SYMPTOMS

. Since

    cardiac amyloidosis
    DIAGNOSIS

 was suspected, the patient underwent

    cardiac magnetic resonance imaging
    PARACLINICAL

 and

    99mTc-pyrophosphate scintigraphy
    PARACLINICAL

. These results are consistent with

    transthyretin amyloidosis (ATTR amyloidosis)
    DIAGNOSIS

.

    DNA analysis of transthyretin (TTR)
    PARACLINICAL

 was performed and a

    heterozygous Val122Ile mutation
    GENETICS

 was identified. Notably,

    his
    GENDER

 only

    son
    GENDER

 requested the analysis; however,

    no mutations were noted
    NEG_FINDINGS

.

    ATTR Val122Ile
    GENETICS

 is one of the

    mutations in TTR
    GENETICS

 that are associated with

    hereditary amyloidosis
    DIAGNOSIS

, causing

    severe cardiomyopathy
    SYMPTOMS

. The prevalence of the

    ATTR Val122Ile mutation
    GENETICS

 is 3.9% in the

    African-American
    ETHNICITY

 population. However, the occurrence of this mutation in

    Asian
    ETHNICITY

 populations is very rare. This is the second reported case of the

    ATTR Val122Ile variant
    GENETICS

 in

    Japan
    ETHNICITY

 and the first case tested including

    familial genes
    PARACLINICAL

. <Learning objective:

    Transthyretin amyloidosis (ATTR) Val122Ile variant
    DIAGNOSIS

 is rare in

    Asian
    ETHNICITY

 people. This is the second case of

    ATTR Val122Ile variant
    DIAGNOSIS

 in

    Japan
    ETHNICITY

 and the first case tested including

    familial genes
    PARACLINICAL

. This case suggests this mutation is present even in

    Asian
    ETHNICITY

 people. It is important to evaluate

    transthyretin gene mutations
    GENETICS

 even in elderly

    ATTR cardiac amyloid
    DIAGNOSIS

    without apparent family history of amyloidosis
    NEG_FINDINGS

. If there is a

    gene mutation
    GENETICS

, it is necessary to search for transthyretin mutation within the family members.>.

Japanese African-American Asian Japan Asian Japan Asian

heterozygous Val122Ile mutation
ATTR Val122Ile
mutations in TTR
ATTR Val122Ile mutation
ATTR Val122Ile variant
transthyretin gene mutations
gene mutation


Negative bone scintigraphy in wild-type transthyretin cardiac amyloidosis.

Amyloidosis is a rare systemic disease due to the extracellular tissue deposition of a fibrillar-shaped misfolded protein, called amyloid. Only two types of proteins commonly affect the heart leading to an infiltrative cardiomyopathy: immunoglobulin light chain and transthyretin (TTR) cardiac amyloidosis (CA). Despite the promising role of emerging imaging modalities, such as strain echocardiography, cardiac magnetic resonance and bone scintigraphy, its diagnosis is still often missed or delayed due to their inherent limitations and to a nonspecific clinical scenario with frequent concomitance of cardiac comorbidities. The gold standard for a definite diagnosis still remains endomyocardial biopsy, but in rare cases Congo Red staining could provide false negative results, as in our case, requiring immunoelectron microscopy.

A middle-aged male adult presented to the emergency department for relapse of heart failure. Echocardiography and cardiac magnetic resonance, along with the history of bilateral carpal tunnel syndrome, were suspicious for TTR-CA. The diagnosis, however, was hampered by concomitant cardiac comorbidities and conflicting results of imaging modalities. In fact bone scintigraphy was negative, as well as Congo Red Staining on myocardial tissue samples obtained by endomyocardial biopsy. Given the high clinical suspicion, immunoelectron microscopy was performed, showing TTR amyloid fibrils deposits, that confirmed the diagnosis. A genetic analysis excluded and hereditary form. The patient was then referred to a specialist center for specific treatment.

This is a rare case of a TTR-CA with a negative Bone Scintigraphy and Congo red staining, which demonstrated that CA is frequently misdiagnosed because of the low specific clinical manifestations and the results of imaging modalities that sometimes could be misleading, with subsequent delayed diagnosis and correct treatment.

    Amyloidosis
    DIAGNOSIS

 is a rare

    systemic disease
    DIAGNOSIS

 due to the

    extracellular tissue deposition of a fibrillar-shaped misfolded protein, called amyloid
    MICROSCOPIC

. Only two types of proteins commonly affect the heart leading to an

    infiltrative cardiomyopathy
    DIAGNOSIS

:

    immunoglobulin light chain and transthyretin (TTR) cardiac amyloidosis (CA)
    DIAGNOSIS

. Despite the promising role of emerging imaging modalities, such as

    strain echocardiography
    PARACLINICAL

,

    cardiac magnetic resonance
    PARACLINICAL

 and

    bone scintigraphy
    PARACLINICAL

, its diagnosis is still often missed or delayed due to their inherent limitations and to a nonspecific clinical scenario with frequent concomitance of

    cardiac comorbidities
    SYMPTOMS

. The gold standard for a definite diagnosis still remains

    endomyocardial biopsy
    PARACLINICAL

, but in rare cases

    Congo Red staining
    PARACLINICAL

 could provide

    false negative results
    NEG_FINDINGS

, as in our case, requiring

    immunoelectron microscopy
    PARACLINICAL

.

A

    middle-aged
    AGE

    male
    GENDER

    adult
    AGE

 presented to the emergency department for

    relapse of heart failure
    SYMPTOMS

.

    Echocardiography
    PARACLINICAL

 and

    cardiac magnetic resonance
    PARACLINICAL

, along with the history of

    bilateral carpal tunnel syndrome
    SYMPTOMS

, were suspicious for

    TTR-CA
    DIAGNOSIS

. The diagnosis, however, was hampered by

    concomitant cardiac comorbidities
    SYMPTOMS

 and

    conflicting results of imaging modalities
    NEG_FINDINGS

. In fact

    bone scintigraphy was negative
    NEG_FINDINGS

, as well as

    Congo Red Staining on myocardial tissue samples obtained by endomyocardial biopsy
    PARACLINICAL

. Given the high clinical suspicion,

    immunoelectron microscopy
    PARACLINICAL

 was performed, showing

    TTR amyloid fibrils deposits
    MICROSCOPIC

, that confirmed the diagnosis. A

    genetic analysis excluded
    PARACLINICAL

 and

    hereditary form
    GENETICS

. The patient was then referred to a specialist center for

    specific treatment
    MEDICATION

.

This is a rare case of a

    TTR-CA
    DIAGNOSIS

 with a

    negative Bone Scintigraphy and Congo red staining
    NEG_FINDINGS

, which demonstrated that

    CA
    DIAGNOSIS

 is frequently

    misdiagnosed
    NEG_FINDINGS

 because of the

    low specific clinical manifestations
    NEG_FINDINGS

 and the results of imaging modalities that sometimes could be misleading, with subsequent delayed diagnosis and correct treatment.

cardiac comorbidities
relapse of heart failure
bilateral carpal tunnel syndrome
concomitant cardiac comorbidities


Cardiac amyloidosis possibly secondary to Agent Orange exposure.

Much research has focused on the association between the toxic metabolites of the tactical herbicide Agent Orange and several blood cancers, including systemic amyloid light-chain (AL) amyloidosis. Here we present a rare case of heart failure secondary to cardiac AL amyloidosis as a consequence of Agent Orange exposure. An elderly man was transferred to the intensive care unit for a suspected gastrointestinal bleed and decompensation of congestive heart failure. An echocardiogram suggested restrictive cardiomyopathy, and an abdominal fat pad biopsy confirmed amyloid involvement. The diagnosis of systemic AL amyloidosis was made following a free lambda to free kappa light chain ratio >3:1. Upon discussion with the patient, significant exposure to Agent Orange during deployment was affirmed. Subsequent care was taken over by the Veterans Affairs Medical Center.

Much research has focused on the association between the

    toxic metabolites of the tactical herbicide Agent Orange
    SYMPTOMS

 and several

    blood cancers
    DIAGNOSIS

, including

    systemic amyloid light-chain (AL) amyloidosis
    DIAGNOSIS

. Here we present a rare case of

    heart failure
    SYMPTOMS

 secondary to

    cardiac AL amyloidosis
    DIAGNOSIS

 as a consequence of

    Agent Orange exposure
    MEDICATION

. An

    elderly
    AGE

    man
    GENDER

 was

    transferred to the intensive care unit
    MEDICATION

 for a suspected

    gastrointestinal bleed
    SYMPTOMS

 and

    decompensation of congestive heart failure
    SYMPTOMS

. An

    echocardiogram
    PARACLINICAL

 suggested

    restrictive cardiomyopathy
    SYMPTOMS

, and an

    abdominal fat pad biopsy
    PARACLINICAL

 confirmed

    amyloid involvement
    MICROSCOPIC

. The diagnosis of

    systemic AL amyloidosis
    DIAGNOSIS

 was made following a

    free lambda to free kappa light chain ratio >3:1
    BIOCHEMICAL

. Upon discussion with the patient,

    significant exposure to Agent Orange during deployment
    SYMPTOMS

 was affirmed. Subsequent care was taken over by the

    Veterans Affairs Medical Center
    MEDICATION

.

Agent Orange exposure
transferred to the intensive care unit
Veterans Affairs Medical Center


A case of unilateral shoulder joint hydrarthrosis with wild-type amyloidogenic transthyretin amyloidosis.

Wild-type amyloidogenic transthyretin (ATTR) amyloidosis, known as systemic senile amyloidosis (SSA), is an age-related nonhereditary amyloidosis, which is known to cause cardiomyopathy and carpal tunnel syndrome (CTS). Herein, we report a case of unilateral hydrarthrosis with arthritis of the right shoulder joint in an 82-year-old Japanese housewife who has a seven year history of polyneuropathy due to an unknown aetiology. At first, her joint pain was thought to be caused by overuse of her right upper arm. Despite treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and repeated arthrocentesis, her symptoms did not improve. She then visited our hospital, where magnetic resonance imaging (MRI) of her right shoulder suggested synovitis and hydrarthrosis. She also had an arthroscopic synovectomy of the right shoulder joint. The pathological testing revealed a diagnosis of non-specific arthritis with amyloidosis. After further pathological examination, wild-type ATTR was identified and she was diagnosed with senile amyloidosis.

    Wild-type amyloidogenic transthyretin (ATTR) amyloidosis
    DIAGNOSIS

, known as

    systemic senile amyloidosis (SSA)
    DIAGNOSIS

, is an age-related

    nonhereditary amyloidosis
    DIAGNOSIS

, which is known to cause

    cardiomyopathy
    SYMPTOMS

 and

    carpal tunnel syndrome (CTS)
    DIAGNOSIS

. Herein, we report a case of

    unilateral hydrarthrosis with arthritis of the right shoulder joint
    SYMPTOMS

 in an

    82-year-old
    AGE

    Japanese
    ETHNICITY

    housewife
    ETHNICITY

 who has a

    seven year history of polyneuropathy due to an unknown aetiology
    FAMILY

. At first,

    her
    GENDER

    joint pain
    SYMPTOMS

 was thought to be caused by

    overuse of her right upper arm
    SYMPTOMS

.

    Despite treatment with non-steroidal anti-inflammatory drugs (NSAIDs)
    NEG_FINDINGS

 and

    repeated arthrocentesis
    MEDICATION

,

    her
    GENDER

    symptoms did not improve
    NEG_FINDINGS

.

    She
    GENDER

 then visited our hospital, where

    magnetic resonance imaging (MRI) of her right shoulder
    PARACLINICAL

 suggested

    synovitis
    SYMPTOMS

 and

    hydrarthrosis
    SYMPTOMS

.

    She
    GENDER

 also had an

    arthroscopic synovectomy of the right shoulder joint
    MEDICATION

. The

    pathological testing
    PARACLINICAL

 revealed a diagnosis of

    non-specific arthritis with amyloidosis
    DIAGNOSIS

. After further

    pathological examination
    PARACLINICAL

,

    wild-type ATTR
    GENETICS

 was identified and

    she
    GENDER

 was diagnosed with

    senile amyloidosis
    DIAGNOSIS

.


Isolated atrial amyloidosis suspected by electrophysiological voltage mapping and diagnosed by 99m Tc-DPD scintigraphy.

We present not-yet-seen multimodal images of a 55-year-old female patient with isolated atrial amyloidosis (IAA) who clinically suffered from multiple atrial arrhythmias and heart failure symptoms with preserved left ventricular ejection fraction. We aim to show structural and functional abnormalities detected by electrophysiological voltage mapping, cardiac magnetic resonance imaging (MRI) [cMRI; atrial strain measurements, late gadolinium enhancement (LGE) visualization], and 99m Tc-DPD scintigraphy. Bipolar voltage mapping performed during two electrophysiological procedures showed diffuse left atrial low-voltage areas (bipolar < 0.5 mV) and also a moderately diseased right atrium suspected of infiltrative cardiomyopathy. Catheter ablation did successfully treat a left atrial and two right atrial focal tachycardias. For further diagnostics, a 3T cMRI was performed, revealing a subendocardial circumferential left atrial LGE and pathological atrial strain measurements, especially during conduit and reservoir phase. Afterwards, nuclear imaging with 559 MBq of 99m Tc-DPD was performed. The scan revealed amyloid infiltration of the left atrium. Neither an uptake in the ventricular myocardium nor an extra-cardiac uptake of DPD was seen. Genetic testing for transthyretin amyloidosis mutations in this patient was negative, and peripheral neuropathy was ruled out by electromyogram analysis. The synopsis of these findings reveals IAA as the most possible diagnosis and showed isolated atrial nuclear tracer uptake with 99m Tc-DPD scintigraphy for the first time. Non-invasive imaging techniques might help in suggesting IAA but need further investigation.

We present not-yet-seen multimodal images of a

    55-year-old
    AGE

    female
    GENDER

 patient with

    isolated atrial amyloidosis (IAA)
    DIAGNOSIS

 who clinically suffered from

    multiple atrial arrhythmias
    SYMPTOMS

 and

    heart failure symptoms
    SYMPTOMS

 with

    preserved left ventricular ejection fraction
    SYMPTOMS

. We aim to show

    structural and functional abnormalities
    SYMPTOMS

 detected by

    electrophysiological voltage mapping
    PARACLINICAL

,

    cardiac magnetic resonance imaging (MRI) [cMRI; atrial strain measurements
    PARACLINICAL

,

    late gadolinium enhancement (LGE) visualization
    PARACLINICAL

], and

    99m Tc-DPD scintigraphy
    PARACLINICAL

.

    Bipolar voltage mapping
    PARACLINICAL

 performed during two

    electrophysiological procedures
    PARACLINICAL

 showed

    diffuse left atrial low-voltage areas (bipolar < 0.5 mV)
    SYMPTOMS

 and also a

    moderately diseased right atrium suspected of infiltrative cardiomyopathy
    SYMPTOMS

.

    Catheter ablation
    MEDICATION

 did successfully

    treat a left atrial and two right atrial focal tachycardias
    SYMPTOMS

. For further diagnostics, a

    3T cMRI
    PARACLINICAL

 was performed, revealing a

    subendocardial circumferential left atrial LGE
    SYMPTOMS

 and

    pathological atrial strain measurements, especially during conduit and reservoir phase
    SYMPTOMS

. Afterwards,

    nuclear imaging with 559 MBq of 99m Tc-DPD
    PARACLINICAL

 was performed. The scan revealed

    amyloid infiltration of the left atrium
    MICROSCOPIC

.

    Neither an uptake in the ventricular myocardium nor an extra-cardiac uptake of DPD was seen
    NEG_FINDINGS

.

    Genetic testing for transthyretin amyloidosis mutations in this patient was negative
    NEG_FINDINGS

, and

    peripheral neuropathy was ruled out by electromyogram analysis
    NEG_FINDINGS

. The synopsis of these findings reveals

    IAA
    DIAGNOSIS

 as the most possible diagnosis and showed

    isolated atrial nuclear tracer uptake
    SYMPTOMS

 with

    99m Tc-DPD scintigraphy
    PARACLINICAL

 for the first time.

    Non-invasive imaging techniques
    PARACLINICAL

 might help in suggesting

    IAA
    DIAGNOSIS

 but need further investigation.

isolated atrial amyloidosis (IAA)
IAA
IAA


Late-onset Hereditary ATTR Amyloidosis with a Novel p.P63S (P43S) Transthyretin Variant.

The patient was an 82-year-old Japanese man with no family history suggestive of amyloidosis. He developed bilateral leg edema and shortness of breath and was referred to our hospital. An electrocardiogram showed atrial fibrillation with right bundle branch block. Echocardiography showed concentric LV hypertrophy. An endomyocardial biopsy showed severe ATTR amyloid deposits. A genetic analysis of the transthyretin (TTR) gene revealed a heterozygous c.187C>T missense variant resulting in p.P63S (P43S). In silico analyses predicted that this variant only modestly altered the structure and function of the TTR protein. The p.P63S variant might be associated with an elderly-onset cardiac-dominant ATTRv phenotype.

The patient was an

    82-year-old
    AGE

    Japanese
    ETHNICITY

    man
    GENDER

 with

    no family history suggestive of amyloidosis
    NEG_FINDINGS

.

    He
    GENDER

 developed

    bilateral leg edema
    SYMPTOMS

 and

    shortness of breath
    SYMPTOMS

 and was referred to our hospital. An

    electrocardiogram
    PARACLINICAL

 showed

    atrial fibrillation with right bundle branch block
    SYMPTOMS

.

    Echocardiography
    PARACLINICAL

 showed

    concentric LV hypertrophy
    SYMPTOMS

. An

    endomyocardial biopsy
    PARACLINICAL

 showed

    severe ATTR amyloid deposits
    MICROSCOPIC

. A

    genetic analysis of the transthyretin (TTR) gene
    PARACLINICAL

 revealed a

    heterozygous c.187C>T missense variant resulting in p.P63S (P43S)
    GENETICS

.

    In silico analyses
    PARACLINICAL

 predicted that this

    variant only modestly altered the structure and function of the TTR protein
    GENETICS

. The

    p.P63S variant
    GENETICS

 might be associated with an

    elderly-onset cardiac-dominant ATTRv
    DIAGNOSIS

 phenotype.


[Two elderly cases of transthyretin amyloid polyneuropathy without a family history].

We report two cases of transthyretin familial amyloid polyneuropathy (ATTR-FAP) from non-endemic areas. Both cases showed chronic progressive distal limb numbness and weakness. Due to nonspecific symptoms, they were not diagnosed for a long period of time. A nerve conduction study revealed axonal neuropathy in the lower limbs and carpal tunnel syndrome. An echo test showed thickness of the left ventricle, one of the red flag symptom clusters of ATTR-FAP. Genetic analysis revealed a mutation in the transthyretin gene. In cases with chronic progressive neuropathy, it is important to consider a differential diagnosis of ATTR-FAP.

We report two cases of

    transthyretin familial amyloid polyneuropathy (ATTR-FAP)
    DIAGNOSIS

 from non-endemic areas. Both cases showed

    chronic progressive distal limb numbness
    SYMPTOMS

 and

    weakness
    SYMPTOMS

. Due to

    nonspecific symptoms
    NEG_FINDINGS

, they were

    not diagnosed for a long period of time
    NEG_FINDINGS

. A

    nerve conduction study
    PARACLINICAL

 revealed

    axonal neuropathy in the lower limbs
    SYMPTOMS

 and

    carpal tunnel syndrome
    SYMPTOMS

. An

    echo test
    PARACLINICAL

 showed

    thickness of the left ventricle
    SYMPTOMS

, one of the red flag symptom clusters of

    ATTR-FAP
    DIAGNOSIS

.

    Genetic analysis
    PARACLINICAL

 revealed a

    mutation in the transthyretin gene
    GENETICS

. In cases with

    chronic progressive neuropathy
    SYMPTOMS

, it is important to consider a

    differential diagnosis
    PARACLINICAL

 of

    ATTR-FAP
    DIAGNOSIS

.

nonspecific symptoms
not diagnosed for a long period of time


Refractory Heart Failure of Unknown Etiology May Be Cardiac Amyloid If Preceded by Hereditary Neurological Symptoms.

Transthyretin cardiac amyloidosis results from the deposition of transthyretin amyloid fibrils in the myocardium. This happens because of the misfolding of genetically normal (wild type - ATTR) or mutant (hereditary ATTR) transthyretin. The clinical presentation of hereditary ATTR cardiac amyloidosis is dependent on the exact site of the amino acid substitution. The V122I gene mutation is most common among people of African descent and usually manifests with cardiomyopathy. The mutations are transmitted in an autosomal dominant manner with variable penetrance and associated with clinical features occurring most commonly after the age of 40. The symptoms of heart failure (HF) may be preceded by several years of vague neurological symptoms which is more concerning if there is no clear explanation. A high index of suspicion is therefore crucial in ensuring prompt diagnosis and therapy, as this may favorably alter the gloomy prognosis associated with cardiac amyloidosis.

    Transthyretin cardiac amyloidosis
    DIAGNOSIS

 results from the

    deposition of transthyretin amyloid fibrils in the myocardium
    MICROSCOPIC

. This happens because of the misfolding of

    genetically normal (wild type - ATTR) or mutant (hereditary ATTR) transthyretin
    GENETICS

. The clinical presentation of

    hereditary ATTR cardiac amyloidosis
    DIAGNOSIS

 is dependent on the exact site of the

    amino acid substitution
    GENETICS

. The

    V122I gene mutation
    GENETICS

 is most common among people of

    African descent
    ETHNICITY

 and usually manifests with

    cardiomyopathy
    DIAGNOSIS

. The

    mutations are transmitted in an autosomal dominant manner
    GENETICS

 with

    variable penetrance
    GENETICS

 and associated with clinical features occurring most commonly

    after the age of 40
    AGE

. The symptoms of

    heart failure (HF)
    SYMPTOMS

 may be preceded by

    several years of vague neurological symptoms
    SYMPTOMS

 which is more concerning if there is

    no clear explanation
    NEG_FINDINGS

. A high index of suspicion is therefore crucial in ensuring prompt diagnosis and therapy, as this may favorably alter the gloomy prognosis associated with

    cardiac amyloidosis
    DIAGNOSIS

.

Transthyretin cardiac amyloidosis
hereditary ATTR cardiac amyloidosis
cardiomyopathy
cardiac amyloidosis


Wild-type Transthyretin Amyloid Myopathy With an Inclusion Body Myositis Phenotype.

Senile systemic amyloidosis (SSA), or wild-type transthyretin (wtATTR) amyloidosis, is associated most commonly with cardiomyopathy and carpal tunnel syndrome. SSA-associated skeletal myopathy is rare. We describe the case of a patient with SSA who exhibited asymmetric quadriceps and finger flexor weakness, a phenotype usually seen in inclusion body myositis.

    Senile systemic amyloidosis (SSA)
    DIAGNOSIS

, or

    wild-type transthyretin (wtATTR) amyloidosis
    DIAGNOSIS

, is associated most commonly with

    cardiomyopathy
    SYMPTOMS

 and

    carpal tunnel syndrome
    DIAGNOSIS

.

    SSA-associated skeletal myopathy
    DIAGNOSIS

 is rare. We describe the case of a patient with

    SSA
    DIAGNOSIS

 who exhibited

    asymmetric quadriceps and finger flexor weakness
    SYMPTOMS

, a phenotype usually seen in

    inclusion body myositis
    DIAGNOSIS

.


Cardiorenal Amyloidosis.

Amyloidosis is a conglomeration of diseases due to production and deposition of amyloid, a proteinaceous substance, into organs, tissues, nerves and other places in the body affecting their normal function. This case report is of a 65 year old gentleman, resident of Bihar admitted with a short history of two months. He came with chief complaints of swelling in both lower limbs associated with heaviness in legs, shortness of breath, dizziness, fatigue and passage of frothy urine for two months. He was investigated and found to have proteinuria, low voltage ECG, Echocardiography showed left ventricular hypertrophy, diastolic dysfunction, mitral regurgitation. Cardiac MRI showed dilated cardiomyopathy due to amyloidosis.

    Amyloidosis
    DIAGNOSIS

 is a conglomeration of diseases due to

    production and deposition of amyloid, a proteinaceous substance, into organs, tissues, nerves and other places in the body
    MICROSCOPIC

 affecting their normal function. This case report is of a

    65 year old
    AGE

    gentleman
    GENDER

, resident of

    Bihar
    ETHNICITY

 admitted with a

    short history of two months
    SYMPTOMS

.

    He
    GENDER

 came with chief complaints of

    swelling in both lower limbs
    SYMPTOMS

 associated with

    heaviness in legs
    SYMPTOMS

,

    shortness of breath
    SYMPTOMS

,

    dizziness
    SYMPTOMS

,

    fatigue
    SYMPTOMS

 and

    passage of frothy urine for two months
    SYMPTOMS

.

    He
    GENDER

 was investigated and found to have

    proteinuria
    BIOCHEMICAL

,

    low voltage ECG
    SYMPTOMS

,

    Echocardiography
    PARACLINICAL

 showed

    left ventricular hypertrophy
    SYMPTOMS

,

    diastolic dysfunction
    SYMPTOMS

,

    mitral regurgitation
    SYMPTOMS

.

    Cardiac MRI
    PARACLINICAL

 showed

    dilated cardiomyopathy
    DIAGNOSIS

 due to

    amyloidosis
    DIAGNOSIS

.

Amyloidosis
dilated cardiomyopathy
amyloidosis

short history of two months
swelling in both lower limbs
heaviness in legs
shortness of breath
dizziness
fatigue
passage of frothy urine for two months
low voltage ECG
left ventricular hypertrophy
diastolic dysfunction
mitral regurgitation


In the midst of a dangerous intersection with unclear therapeutic strategies: a challenging case of severe aortic stenosis.

One out of seven patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) may be affected by transthyretin cardiac amyloidosis (ATTR-CA), mostly presenting with low-flow low-gradient AS with mildly reduced ejection fraction. The complex interaction of these two pathologies poses specific diagnostic and management challenges. The prognostic implications of this clinical intersection are not defined yet. Moreover, whether TAVR may have a prognostic benefit in ATTR-CA patients with symptomatic severe AS remains unclear, posing doubts on the best management strategy in this increasingly recognized subset of patients.

We present a case of an 87-year old man with low-flow low-gradient severe AS, for whom a diagnosis of ATTR-CA was suspected based on clinical and echocardiographic criteria specific to coexisting AS and ATTR-CA. The diagnosis was eventually confirmed by positive bone tracer scintigraphy imaging. Following in-depth Heart team discussion, integrating frailty and prognostic information from combined cardiomyopathy states, a decision was made to manage the patient's severe AS conservatively.

In the presented case, we deemed the natural history of ATTR-CA amyloidosis to negatively affect both the patient' prognosis and procedural risk, adversing TAVR indication despite symptomatic severe AS. No clear evidence is currently available to guide decision making in this setting, advocating for prospective studies to clarify if TAVR may have a prognostic benefit in ATTR-CA - and which ATTR-CA - patients.

One out of seven patients with

    severe aortic stenosis (AS)
    DIAGNOSIS

 undergoing

    transcatheter aortic valve replacement (TAVR)
    MEDICATION

 may be affected by

    transthyretin cardiac amyloidosis (ATTR-CA)
    DIAGNOSIS

, mostly presenting with

    low-flow low-gradient AS
    SYMPTOMS

 with

    mildly reduced ejection fraction
    SYMPTOMS

. The complex interaction of these two pathologies poses specific diagnostic and management challenges. The prognostic implications of this clinical intersection are not defined yet. Moreover, whether

    TAVR
    MEDICATION

 may have a prognostic benefit in

    ATTR-CA
    DIAGNOSIS

 patients with

    symptomatic severe AS
    DIAGNOSIS

 remains unclear, posing doubts on the best management strategy in this increasingly recognized subset of patients.

We present a case of an

    87-year old
    AGE

    man
    GENDER

 with

    low-flow low-gradient severe AS
    SYMPTOMS

, for whom a diagnosis of

    ATTR-CA
    DIAGNOSIS

 was suspected based on clinical and echocardiographic criteria specific to

    coexisting AS and ATTR-CA
    SYMPTOMS

. The diagnosis was eventually confirmed by

    positive bone tracer scintigraphy imaging
    PARACLINICAL

. Following in-depth

    Heart team discussion
    PARACLINICAL

, integrating frailty and prognostic information from

    combined cardiomyopathy states
    SYMPTOMS

, a decision was made to

    manage
    MEDICATION

 the patient's

    severe AS
    DIAGNOSIS

    conservatively
    MEDICATION

.

In the presented case, we deemed the natural history of

    ATTR-CA amyloidosis
    DIAGNOSIS

 to negatively affect both the patient' prognosis and procedural risk,

    adversing TAVR indication despite symptomatic severe AS
    NEG_FINDINGS

. No clear evidence is currently available to guide decision making in this setting, advocating for prospective studies to clarify if

    TAVR
    MEDICATION

 may have a prognostic benefit in

    ATTR-CA -
    DIAGNOSIS

 and which

    ATTR-CA -
    DIAGNOSIS

 patients.

low-flow low-gradient AS
mildly reduced ejection fraction
low-flow low-gradient severe AS
coexisting AS and ATTR-CA
combined cardiomyopathy states


Cardiac AA amyloidosis in a patient with obstructive hypertrophic cardiomyopathy.

Cardiac amyloid A (AA) amyloidosis is rare. We present the case of a 72-year-old woman with obstructive hypertrophic cardiomyopathy (HCM) and biopsy-proven renal AA amyloidosis whose dyspnea and exercise intolerance had worsened over the previous year. Her AA amyloidosis was suspected to be secondary to chronic diverticulitis for which she had undergone hemicolectomy and sigmoidectomy 3 years prior. Echocardiographic findings were consistent with worsening left ventricular outflow tract obstruction at rest. Cardiac magnetic resonance imaging revealed patchy areas of midwall late gadolinium enhancement. Right ventricular endomyocardial biopsy did not reveal amyloid deposition, and cardiac technetium-99m pyrophosphate scintigraphy did not suggest transthyretin amyloidosis. The patient underwent septal myectomy with resection of an accessory papillary muscle. Pathological examination of the myectomy specimen was consistent with HCM. In addition, there was a thick layer of diffuse endocardial and vascular amyloid deposition that was identified as AA type by laser-microdissection with liquid chromatography-coupled tandem-mass spectrometry. This case report highlights the presence of 2 distinct disease processes occurring simultaneously and the importance of tissue diagnosis of AA amyloidosis, a condition that is not commonly associated with HCM.

    Cardiac amyloid A (AA) amyloidosis
    DIAGNOSIS

 is rare. We present the case of a

    72-year-old
    AGE

    woman
    GENDER

 with

    obstructive hypertrophic cardiomyopathy (HCM)
    DIAGNOSIS

 and

    biopsy-proven renal AA amyloidosis
    DIAGNOSIS

 whose

    dyspnea
    SYMPTOMS

 and

    exercise intolerance
    SYMPTOMS

 had worsened over the previous year.

    Her
    GENDER

    AA amyloidosis
    DIAGNOSIS

 was suspected to be secondary to

    chronic diverticulitis
    DIAGNOSIS

 for which

    she
    GENDER

 had

    undergone hemicolectomy and sigmoidectomy
    MEDICATION

 3 years prior.

    Echocardiographic
    PARACLINICAL

 findings were consistent with

    worsening left ventricular outflow tract obstruction at rest
    SYMPTOMS

.

    Cardiac magnetic resonance imaging
    PARACLINICAL

 revealed

    patchy areas of midwall late gadolinium enhancement
    SYMPTOMS

.

    Right ventricular endomyocardial biopsy
    PARACLINICAL

    did not reveal amyloid deposition
    NEG_FINDINGS

, and

    cardiac technetium-99m pyrophosphate scintigraphy
    PARACLINICAL

    did not suggest transthyretin amyloidosis
    NEG_FINDINGS

. The patient underwent

    septal myectomy with resection of an accessory papillary muscle
    MEDICATION

.

    Pathological examination of the myectomy specimen
    PARACLINICAL

 was consistent with

    HCM
    DIAGNOSIS

. In addition, there was a

    thick layer of diffuse endocardial and vascular amyloid deposition
    MICROSCOPIC

 that was identified as

    AA type
    MICROSCOPIC

 by

    laser-microdissection with liquid chromatography-coupled tandem-mass spectrometry
    PARACLINICAL

. This case report highlights the presence of 2 distinct disease processes occurring simultaneously and the importance of

    tissue diagnosis
    PARACLINICAL

 of

    AA amyloidosis
    DIAGNOSIS

, a condition that is not commonly associated with

    HCM
    DIAGNOSIS

.


Cases from a busy nuclear cardiology laboratory: Potential pitfalls in the interpretation of cardiac scintigraphy for ATTR cardiac amyloidosis.

Cardiac scintigraphy has emerged as a key diagnostic test for transthyretin cardiac amyloidosis (ATTR-CA). However, there are potential limitations and pitfalls in the interpretation of cardiac scintigraphy for ATTR-CA that are worth noting. We present here a series of three cases which illustrate some of these important principles.

    Cardiac scintigraphy
    PARACLINICAL

 has emerged as a key diagnostic test for

    transthyretin cardiac amyloidosis (ATTR-CA)
    DIAGNOSIS

. However, there are potential limitations and pitfalls in the interpretation of

    cardiac scintigraphy
    PARACLINICAL

 for

    ATTR-CA
    DIAGNOSIS

 that are worth noting. We present here a series of three cases which illustrate some of these important principles.


Hereditary transthyretin amyloidosis caused by the rare Phe33Leu mutation.

Hereditary transthyretin amyloidosis is a rare progressive systemic disease. We describe a physically active 46-year-old man who presented with dyspnoea on exertion. An echocardiogram showed increased left ventricular wall thickness and diastolic dysfunction, but normal systolic function. The QRS voltage on ECG was normal. The patient was diagnosed with hypertrophic cardiomyopathy, and several years passed before establishment of the accurate diagnosis of hereditary transthyretin amyloidosis caused by the rare mutation ATTR Phe33Leu, previously described in only five case reports. Further investigation revealed neuropathy and nephropathy, and the patient developed severe heart failure. The patient is treated with tafamidis, has undergone heart transplantation and is currently planned for liver transplant. Hereditary transthyretin amyloidosis is likely underdiagnosed, especially in patients presenting with cardiomyopathy. A discrepancy between the left ventricular mass indicated by echocardiogram and that on ECG is an important indicator of amyloidosis, as is involvement of multiple organs.

    Hereditary transthyretin amyloidosis
    DIAGNOSIS

 is a

    rare progressive systemic disease
    DIAGNOSIS

. We describe a

    physically active
    MEDICATION

    46-year-old
    AGE

    man
    GENDER

 who presented with

    dyspnoea on exertion
    SYMPTOMS

. An

    echocardiogram
    PARACLINICAL

 showed

    increased left ventricular wall thickness
    SYMPTOMS

 and

    diastolic dysfunction
    SYMPTOMS

, but

    normal systolic function
    NEG_FINDINGS

.

    The QRS voltage on ECG was normal
    NEG_FINDINGS

. The patient was diagnosed with

    hypertrophic cardiomyopathy
    DIAGNOSIS

, and several years passed before establishment of the accurate diagnosis of

    hereditary transthyretin amyloidosis
    DIAGNOSIS

 caused by the

    rare mutation ATTR Phe33Leu
    GENETICS

, previously described in only five case reports. Further investigation revealed

    neuropathy
    SYMPTOMS

 and

    nephropathy
    DIAGNOSIS

, and the patient developed

    severe heart failure
    SYMPTOMS

. The patient is treated with

    tafamidis
    MEDICATION

,

    has undergone heart transplantation
    MEDICATION

 and is currently

    planned for liver transplant
    MEDICATION

.

    Hereditary transthyretin amyloidosis
    DIAGNOSIS

 is likely underdiagnosed, especially in patients presenting with

    cardiomyopathy
    DIAGNOSIS

. A

    discrepancy between the left ventricular mass indicated by echocardiogram and that on ECG
    SYMPTOMS

 is an important indicator of

    amyloidosis
    DIAGNOSIS

, as is

    involvement of multiple organs
    SYMPTOMS

.

Hereditary transthyretin amyloidosis
rare progressive systemic disease
hypertrophic cardiomyopathy
hereditary transthyretin amyloidosis
nephropathy
Hereditary transthyretin amyloidosis
cardiomyopathy
amyloidosis

physically active
tafamidis
has undergone heart transplantation
planned for liver transplant

normal systolic function
The QRS voltage on ECG was normal


Identification and typing of cardiac amyloidosis by noninvasive imaging: Two cases for two patterns.

Cardiac amyloidosis is a restrictive infiltrative cardiomyopathy burdened by high mortality. The two more common forms are immunoglobulin light-chain amyloidosis and transthyretin-related amyloidosis with different prognoses and treatments. However, distinguishing between them is challenging. Appropriate utilization of the different available imaging techniques in the evaluation of patients with known or suspected cardiac amyloidosis is mandatory. We report two cases with cardiac amyloidosis of different etiology and with distinct imaging patterns. In the first case, the negative 99mTc-diphosphonate imaging was useful to support the diagnosis of cardiac amyloid light-chain; the second case emphasized the utility of whole-body scintigraphy in recognizing transthyretin-related cardiac amyloidosis and the potential role of cadmium-zinc-telluride SPECT imaging for the evaluation of segmental distribution of cardiac disease. Both cases support the growing interest in looking for noninvasive methods to type cardiac amyloidosis in the place of invasive myocardial biopsy highlighting both possibilities and limitations of available imaging techniques in diagnosis and treatment monitoring.

    Cardiac amyloidosis
    DIAGNOSIS

 is a

    restrictive infiltrative cardiomyopathy
    DIAGNOSIS

 burdened by high mortality. The two more common forms are

    immunoglobulin light-chain amyloidosis
    DIAGNOSIS

 and

    transthyretin-related amyloidosis
    DIAGNOSIS

 with different prognoses and treatments. However, distinguishing between them is challenging. Appropriate utilization of the different available imaging techniques in the evaluation of patients with known or suspected

    cardiac amyloidosis
    DIAGNOSIS

 is mandatory. We report two cases with

    cardiac amyloidosis
    DIAGNOSIS

 of different etiology and with distinct imaging patterns. In the first case, the

    negative 99mTc-diphosphonate imaging
    NEG_FINDINGS

 was useful to support the diagnosis of

    cardiac amyloid light-chain
    DIAGNOSIS

; the second case emphasized the utility of

    whole-body scintigraphy
    PARACLINICAL

 in recognizing

    transthyretin-related cardiac amyloidosis
    DIAGNOSIS

 and the potential role of

    cadmium-zinc-telluride SPECT imaging
    PARACLINICAL

 for the evaluation of

    segmental distribution of cardiac disease
    SYMPTOMS

. Both cases support the growing interest in looking for noninvasive methods to type

    cardiac amyloidosis
    DIAGNOSIS

 in the place of

    invasive myocardial biopsy
    PARACLINICAL

 highlighting both possibilities and limitations of available imaging techniques in diagnosis and treatment monitoring.


Sporadic Cardiac Amyloidosis by Amyloidogenic Transthyretin V122I Variant.

Hereditary ATTR amyloid cardiomyopathy is defined as the intramyocardial deposition of amyloid fibrils derived from the mutation of transthyretin (TTR). A 51-year-old man was referred to our hospital for congestive heart failure. He and his family had no past history of heart diseases. Echocardiography showed remarkable left ventricular hypertrophy and reduced ejection fraction. Endomyocardial biopsy specimens presented positive staining of Congo-Red and transthyretin. A genetic test showed heterozygous V122I TTR gene mutation, which is very rare in Japan. We diagnosed him as with sporadic ATTR amyloidosis with mutation, and tafamidis was administered to stabilize TTR tetramer. Since the phenotype of ATTR amyloidosis varies depending on its penetration rate, it is crucial to always keep in mind the possibility of hereditary ATTR amyloidosis even in the case of amyloidosis with no clear family history.

    Hereditary ATTR amyloid cardiomyopathy
    DIAGNOSIS

 is defined as the

    intramyocardial deposition of amyloid fibrils derived
    MICROSCOPIC

 from the

    mutation of transthyretin (TTR)
    GENETICS

. A

    51-year-old
    AGE

    man
    GENDER

 was referred to our hospital for

    congestive heart failure
    SYMPTOMS

.

    He
    GENDER

 and his

    family had no past history of heart diseases
    FAMILY

.

    Echocardiography
    PARACLINICAL

 showed

    remarkable left ventricular hypertrophy
    SYMPTOMS

 and

    reduced ejection fraction
    SYMPTOMS

.

    Endomyocardial biopsy specimens
    PARACLINICAL

 presented

    positive staining of Congo-Red and transthyretin
    MICROSCOPIC

. A

    genetic test
    PARACLINICAL

 showed

    heterozygous V122I TTR gene mutation
    GENETICS

, which is very rare in

    Japan
    ETHNICITY

. We diagnosed

    him
    GENDER

 as with

    sporadic ATTR amyloidosis
    DIAGNOSIS

 with mutation, and

    tafamidis
    MEDICATION

 was administered to

    stabilize TTR tetramer
    MEDICATION

. Since the phenotype of

    ATTR amyloidosis
    DIAGNOSIS

 varies depending on its penetration rate, it is crucial to always keep in mind the possibility of

    hereditary ATTR amyloidosis
    DIAGNOSIS

 even in the case of

    amyloidosis
    DIAGNOSIS

 with

    no clear family history
    NEG_FINDINGS

.

Hereditary ATTR amyloid cardiomyopathy
sporadic ATTR amyloidosis
ATTR amyloidosis
hereditary ATTR amyloidosis
amyloidosis

mutation of transthyretin (TTR)
heterozygous V122I TTR gene mutation

congestive heart failure
remarkable left ventricular hypertrophy
reduced ejection fraction


Severe hand pain as an extracardiac manifestation of transthyretin amyloidosis.

Transthyretin amyloidosis is a multisystemic disease caused by the aggregation of amyloid fibrils, resulting in high morbidity and mortality in the presence of cardiac involvement. Patients often experience vague symptoms that make amyloidosis difficult to diagnose. Differential diagnosis for hand pain in a patient with systemic amyloidosis is broad. We present a patient with severe hand cramping and inability to perform activities of daily living. This preceded a new diagnosis of familial amyloid cardiomyopathy. The patient was a poor responder to systemic corticosteroids, anti-inflammatories and anticonvulsant therapy. Her unique presentation gives insight into a rare but debilitating disorder and the potential link between amyloidosis and other disease processes.

    Transthyretin amyloidosis
    DIAGNOSIS

 is a

    multisystemic disease
    DIAGNOSIS

 caused by the

    aggregation of amyloid fibrils
    MICROSCOPIC

, resulting in high morbidity and mortality in the presence of

    cardiac involvement
    SYMPTOMS

. Patients often experience

    vague symptoms
    SYMPTOMS

 that make

    amyloidosis
    DIAGNOSIS

 difficult to diagnose.

    Differential diagnosis
    PARACLINICAL

 for

    hand pain
    SYMPTOMS

 in a patient with

    systemic amyloidosis
    DIAGNOSIS

 is broad. We present a patient with

    severe hand cramping
    SYMPTOMS

 and

    inability to perform activities of daily living
    SYMPTOMS

. This preceded a new diagnosis of

    familial amyloid cardiomyopathy
    DIAGNOSIS

. The patient was a

    poor responder to systemic corticosteroids, anti-inflammatories and anticonvulsant therapy
    NEG_FINDINGS

.

    Her
    GENDER

 unique presentation gives insight into a rare but debilitating disorder and the potential link between

    amyloidosis
    DIAGNOSIS

 and other disease processes.

Transthyretin amyloidosis
multisystemic disease
amyloidosis
systemic amyloidosis
familial amyloid cardiomyopathy
amyloidosis


Beneficial Effect of Pimobendan for Severe Heart Failure Due to Transthyretin Cardiac Amyloidosis.

Objective Transthyretin amyloidosis, particularly wild-type transthyretin amyloid cardiomyopathy (ATTRwt), has been recognized as an important cause of morbidity and mortality in the aging population. However, it is difficult to manage heart failure itself in patients with cardiac amyloidosis. Methods We herein report the management of heart failure in an elderly patient with severe heart failure due to ATTRwt. We also review the clinical situation in an additional seven patients with cardiac amyloidosis who were administered pimobendan in our hospital. Results We treated a 71-year-old man with refractory heart failure due to ATTRwt. He was expected to be dependent on dobutamine infusion. We administered pimobendan and successfully improved his symptoms and hemodynamic status to allow his discharge from the hospital. An additional retrospective investigation observed that there were eight patients with ATTR amyloidosis who were administered pimobendan. Although all of the patients at the time of administration of pimobendan were NYHA class III or IV with repeated hospitalization for heart failure, pimobendan seemed to be effective for improving symptoms and enabling patients to be discharged and receive outpatient medical care. Furthermore, focusing on the changes in some biomarkers, we found that the brain natriuretic peptide and estimated glomerular filtration rate values improved after the administration of pimobendan in 5 consecutive patients for whom data were available without additional treatment (p=0.018 and 0.051, respectively). Conclusion In clinical practice, pimobendan seems to have beneficial effects in heart failure management for improving physical activities and the quality of life in patients with transthyretin cardiac amyloidosis.

Objective

    Transthyretin amyloidosis
    DIAGNOSIS

, particularly

    wild-type transthyretin amyloid cardiomyopathy (ATTRwt)
    DIAGNOSIS

, has been recognized as an important cause of morbidity and mortality in the aging population. However, it is difficult to manage

    heart failure
    DIAGNOSIS

 itself in patients with

    cardiac amyloidosis
    DIAGNOSIS

. Methods We herein report the management of

    heart failure
    DIAGNOSIS

 in an

    elderly
    AGE

 patient with

    severe heart failure
    SYMPTOMS

 due to

    ATTRwt
    DIAGNOSIS

. We also review the clinical situation in an additional seven patients with

    cardiac amyloidosis
    DIAGNOSIS

 who were administered

    pimobendan
    MEDICATION

 in our hospital. Results We treated a

    71-year-old
    AGE

    man
    GENDER

 with

    refractory heart failure
    SYMPTOMS

 due to

    ATTRwt
    DIAGNOSIS

.

    He
    GENDER

 was

    expected to be dependent on dobutamine infusion
    NEG_FINDINGS

. We administered

    pimobendan
    MEDICATION

 and successfully

    improved his symptoms and hemodynamic status
    SYMPTOMS

 to allow

    his
    GENDER

    discharge from the hospital
    MEDICATION

. An additional retrospective investigation observed that there were eight patients with

    ATTR amyloidosis
    DIAGNOSIS

 who were administered

    pimobendan
    MEDICATION

. Although all of the patients at the time of

    administration of pimobendan
    MEDICATION

 were

    NYHA class III or IV
    DIAGNOSIS

 with

    repeated hospitalization for heart failure
    MEDICATION

,

    pimobendan
    MEDICATION

 seemed to be effective for

    improving symptoms
    SYMPTOMS

 and enabling patients to be

    discharged and receive outpatient medical care
    MEDICATION

. Furthermore, focusing on the changes in some biomarkers, we found that

    the brain natriuretic peptide and estimated glomerular filtration rate values improved
    BIOCHEMICAL

 after the

    administration of pimobendan
    MEDICATION

 in 5 consecutive patients for whom data were available

    without additional treatment
    NEG_FINDINGS

 (p=0.018 and 0.051, respectively). Conclusion In clinical practice,

    pimobendan
    MEDICATION

 seems to have beneficial effects in

    heart failure
    DIAGNOSIS

 management for

    improving physical activities and the quality of life
    SYMPTOMS

 in patients with

    transthyretin cardiac amyloidosis
    DIAGNOSIS

.


Estimating the fiscal impact of rare diseases using a public economic framework: a case study applied to hereditary transthyretin-mediated (hATTR) amyloidosis.

A wide range of rare diseases can have fiscal impacts on government finances that extend beyond expected healthcare costs. Conditions preventing people from achieving national lifetime work averages will influence lifetime taxes paid and increase the likelihood of dependence on public income support. Consequently, interventions that influence projected lifetime work activity, morbidity and mortality can have positive and negative fiscal consequences for government. The aim of this study was to apply a public economic framework to a rare disease that takes into consideration a broad range of costs that are relevant to government in relation to transfers received and taxes paid. As a case study we constructed a simulation model to calculate the fiscal life course of an individual with hereditary transthyretin-mediated (hATTR) amyloidosis in The Netherlands. In this lethal disease different progressive disease scenarios occur, including polyneuropathy and/or cardiomyopathy.

Due to progressive disability, health care resource use, and early death, hATTR amyloidosis with polyneuropathy receives more transfers from government compared to the general population. In a scenario where a patient is diagnoses with hATTR at age 45, an individual pays €180,812 less in lifetime taxes and receives incrementally €111,695 in transfers from the government, compared to a person without hATTR. Patients suffering from cardiomyopathy die after median 4 years. The health costs of this scenario are therefore lower than that of the other polyneuropathy-based scenarios.

The fiscal analysis illustrates how health conditions influence not only health costs, but also the cross-sectorial public economic burden attributed to lost tax revenues and public disability allowances. Due to the progressive nature of hATTR amyloidosis used in this study, public costs including disability increase as the disease progresses with reduced lifetime taxes paid. The results indicate that halting disease progression early in the disease course would generate fiscal benefits beyond health benefits for patients. This analysis highlights the fiscal consequences of diseases and the need for broader perspectives applied to evaluate health conditions. Conventional cost-effectiveness framework used by many health technology assessment agencies have well-documented limitations in the field of rare diseases and fiscal modeling should be a complementary approach to consider.

A wide range of

    rare diseases
    DIAGNOSIS

 can have fiscal impacts on government finances that extend beyond expected healthcare costs. Conditions preventing people from achieving national lifetime work averages will influence lifetime taxes paid and increase the likelihood of dependence on public

    income support
    MEDICATION

. Consequently, interventions that influence projected lifetime work activity,

    morbidity
    SYMPTOMS

 and mortality can have positive and negative fiscal consequences for government. The aim of this study was to apply a public economic framework to a

    rare disease
    DIAGNOSIS

 that takes into consideration a broad range of costs that are relevant to government in relation to transfers received and taxes paid. As a case study we constructed a simulation model to calculate the fiscal life course of an individual with

    hereditary transthyretin-mediated (hATTR) amyloidosis
    DIAGNOSIS

 in The

    Netherlands
    ETHNICITY

. In this

    lethal disease
    DIAGNOSIS

 different progressive disease scenarios occur, including

    polyneuropathy
    DIAGNOSIS

 and/or

    cardiomyopathy
    DIAGNOSIS

.

Due to

    progressive disability
    SYMPTOMS

,

    health care resource use
    MEDICATION

, and

    early death
    SYMPTOMS

,

    hATTR amyloidosis with polyneuropathy
    DIAGNOSIS

 receives more transfers from government compared to the general population. In a scenario where a patient is diagnoses with

    hATTR
    DIAGNOSIS

 at

    age 45
    AGE

, an individual

    pays €180,812 less in lifetime taxes
    MEDICATION

 and receives incrementally €111,695 in transfers from the government, compared to a person without

    hATTR
    DIAGNOSIS

. Patients suffering from

    cardiomyopathy
    DIAGNOSIS

 die after

    median 4 years
    AGE

. The health costs of this scenario are therefore lower than that of the other

    polyneuropathy
    DIAGNOSIS

-based scenarios.

The

    fiscal analysis
    PARACLINICAL

 illustrates how health conditions influence not only health costs, but also the cross-sectorial public economic burden attributed to lost tax revenues and public disability allowances. Due to the progressive nature of

    hATTR amyloidosis
    DIAGNOSIS

 used in this study, public costs including

    disability
    SYMPTOMS

 increase as the disease progresses with

    reduced lifetime taxes paid
    MEDICATION

. The results indicate that halting disease progression early in the disease course would generate fiscal benefits beyond health benefits for patients. This analysis highlights the fiscal consequences of diseases and the need for broader perspectives applied to evaluate health conditions. Conventional cost-effectiveness framework used by many health technology assessment agencies have well-documented limitations in the field of

    rare diseases
    DIAGNOSIS

 and

    fiscal modeling
    PARACLINICAL

 should be a complementary approach to consider.

income support
health care resource use
pays €180,812 less in lifetime taxes
reduced lifetime taxes paid

morbidity
progressive disability
early death
disability


Where Neurosurgery Meets Heart Failure: A Case Report of a Patient with Amyloid Transthyretin Wild Type in the Ligamentum Flavum and Cardiac Tissue with Bilateral Carpal Tunnel Syndrome.

Transthyretin wild-type (ATTRwt) amyloidosis is a systemic process resulting in deposition of misfolded transthyretin protein in several different tissues throughout the body. It is known to be a cause of progressive, life-threatening cardiomyopathy and lumbar spinal stenosis and carpal tunnel syndrome.

Here we present the case of a 71-year-old man who has clinical manifestations of all 3 entities over several years, providing a picture of the natural history of ATTRwt amyloidosis. This patient eventually underwent a heart transplant because of progressive cardiac amyloidosis (CA) resulting in end-stage heart failure. However, symptoms in carpal tunnel and lumbar spine manifested years before the symptoms of heart failure. ATTRwt amyloidosis may present as a clinical triad of lumbar stenosis, carpal tunnel syndrome, and heart failure. Recently developed medications have shown efficacy in slowing the progress of systemic and cardiac amyloidosis.

Knowing that extracardiac symptoms may occur first, we propose that sending ligamentum flavum and flexor tenosynovium for pathologic evaluation may be a unique opportunity to screen and treat a population of patients at risk for developing CA and heart failure.

    Transthyretin wild-type (ATTRwt) amyloidosis
    DIAGNOSIS

 is a

    systemic process
    DIAGNOSIS

 resulting in

    deposition of misfolded transthyretin protein in several different tissues throughout the body
    MICROSCOPIC

. It is known to be a cause of

    progressive, life-threatening cardiomyopathy
    SYMPTOMS

 and

    lumbar spinal stenosis
    SYMPTOMS

 and

    carpal tunnel syndrome
    DIAGNOSIS

.

Here we present the case of a

    71-year-old
    AGE

    man
    GENDER

 who has

    clinical manifestations of all 3 entities
    SYMPTOMS

 over several years, providing a picture of the natural history of

    ATTRwt amyloidosis
    DIAGNOSIS

. This patient eventually underwent a

    heart transplant
    MEDICATION

 because of

    progressive cardiac amyloidosis (CA)
    DIAGNOSIS

 resulting in

    end-stage heart failure
    DIAGNOSIS

. However,

    symptoms in carpal tunnel and lumbar spine
    SYMPTOMS

 manifested years before the symptoms of

    heart failure
    SYMPTOMS

.

    ATTRwt amyloidosis
    DIAGNOSIS

 may present as a clinical triad of

    lumbar stenosis
    SYMPTOMS

,

    carpal tunnel syndrome
    SYMPTOMS

, and

    heart failure
    SYMPTOMS

. Recently developed medications have shown efficacy in slowing the progress of

    systemic and cardiac amyloidosis
    DIAGNOSIS

.

Knowing that

    extracardiac symptoms
    SYMPTOMS

 may occur first, we propose that

    sending ligamentum flavum and flexor tenosynovium for pathologic evaluation
    PARACLINICAL

 may be a unique opportunity to screen and treat a population of patients at risk for developing CA and

    heart failure
    SYMPTOMS

.