Prevalence of Wild-type TTR Cardiac Amyloidosis in Patients With Polyneuropathy of Unknown Cause.

Prevalence of Wild-type TTR Cardiac Amyloidosis in Patients With Polyneuropathy of Unknown Cause: a Prospective Monocentric Study (CAP-TTR)

To investigate to what extent chronic axonal length-dependent polyneuropathy (CAP) and/or small-fiber neuropathy (SFN) is part of early non-cardiac manifestations of wild-type TTR cardiac amyloidosis (wtTTR-CA). Consequently, explore whether this could ultimately lead to faster diagnosis and clinical outcome of wild-type TTR cardiac amyloidosis (wtTTR-CA).

Patients with chronic axonal length-dependent polyneuropathy (CAP) and/or small-fiber neuropathy (SFN) without well-defined cause will be recruited after a neurological standard routine work-up with NCS (Nerve conduction study) test, EMG, and Sudoscan®, previously performed at the neurology department of UZ-Brussel in normal clinical setting. All participants will be invited to the Neurology and Cardiology department for one visit on one day, for the following assessments: Following exams will be performed: assessment of symptoms, severity, and duration of the polyneuropathy and the use of NTSS-6 and COMPASS31 score for mapping somatosensory and autonomic symptoms evaluation of objective polyneuropathy signs, using following scales: mPND, NIS Kansas City Cardiomyopathy Questionnaire (KCCQ) Electrocardiogram (ECG) Echocardiography The following retrospective data from the medical file will be analyzed: assessment of medical history, medical treatment, and demographic data assessment of laboratory results (and, if applicable, other exams) extracted from the medical file and previously performed in the context of polyneuropathy workup assessment of previously performed NCV/EMG data and Sudoscan®, extracted from the medical file of the participants.

1 arm including patients with chronic axonal length-dependent polyneuropathy and/or small-fiber neuropathy. All participants will be screened with ECG and echocardiography. All participants will be asked to complete questionnaires about there polyneuropathy and cardiological symptoms.

Answering questionnaires about polyneuropathy symptoms (NTSS -6, COMPASS31, NIS, mPND) and also cardialogical symptoms (KCCQ-12).

Primary Outcome: Evaluation of prevalence of wild-type cardiac amyloidosis in our CAP and/or SFN population without well known cause.

Prevalence of cardiac amyloidosis by doing a cardiac screening for wild-type cardiac amyloidosis with performing an echocardiography. Echocardiography criteria: LV wall (>12mm), left ventricular ejection fraction (%), Apical sparing pattern (y/n), diastolic dysfunction (y/n), left atrial volume (ml/m2). Left atrial volume in ml and LA volume in ml/m2, whereby m2 is the body surface area based on weight and height (Mosteller formula).

Primary Outcome: Evaluation of prevalence of wild-type cardiac amyloidosis in our CAP and/or SFN population without well known cause

Prevalence of cardiac amyloidosis by doing a cardiac screening for wild-type cardiac amyloidosis with performing an ECG. ECG criteria: atrial fibrillation (y/n), QRS-duration, low voltage (y/n)

Primary Outcome: Evaluation of prevalence of wild-type cardiac amyloidosis in our CAP and/or SFN population without well known cause

Prevalence of cardiac amyloidosis by doing a cardiac screening for wild-type cardiac amyloidosis with performing a questionnaire (Kansas City Cardiomyopathy Questionnaire). KCCQ-12 has 4 domains (Physical Limitation Score, Symptom Frequency Score, Quality of Life Score, Social Limitation Score) and one Summary Score. Scores are scaled 0-100, where 0 denotes the lowest reportable health status and 100 the highest. This descriptive score will be used as a functional parameter without a cut-off.

Considering the rather small study population and the rarity of wtTTR amyloidosis, statistical analyses cannot be used without massively overfitting the results, which will not be reproducible. The investigators consequently opt for descriptive statistics to compare the group of polyneuropathy patients with wt-Ca and those without wt-CA. Therefore a few parameters are examined. The first scale used therefore is the modified Polyneuropathy Disability score (mPND). This scale is a questionnaire with a few questions about the complaints of the polyneuropathy in the daily life. O means no complaints of the polyneuropathy in daily life, IV means a major impact on the daily life of the patient.

Considering the rather small study population and the rarity of wtTTR amyloidosis, statistical analyses cannot be used without massively overfitting the results, which will not be reproducible. The investigators consequently opt for descriptive statistics to compare the group of polyneuropathy patients with wt-Ca and those without wt-CA. Therefore a few parameters are examined. The second scale used therefore is the Neuropathy Impairment Score (NIS).This scale is a questionnaire with a few questions about the complaints of the polyneuropathy in the daily life. The score is between 0 and 244. O means less complaints in the daily life, 244 means major impact in the daily life of the patient.

Considering the rather small study population and the rarity of wtTTR amyloidosis, statistical analyses cannot be used without massively overfitting the results, which will not be reproducible. The investigators consequently opt for descriptive statistics to compare the group of polyneuropathy patients with wt-Ca and those without wt-CA. Therefore a few parameters are examined. The third scale used therefore is the Neuropathy Total Symptom Score - Health Care professional administered version (NTSS-6). This scale is a questionnaire with a few items about the symptoms of the polyneuropathy in the daily life (aching pain, burning pain, prickling sensation, numbness, lancinating pain and allodynia). Depending on the presence of the symptoms in time and strength, a score will show up. On each symptom you can score a maximum of 3,66. So the total score for this scale is 21,96 if the patients has major complaints in daily life.

Considering the rather small study population and the rarity of wtTTR amyloidosis, statistical analyses cannot be used without massively overfitting the results, which will not be reproducible. The investigators consequently opt for descriptive statistics to compare the group of polyneuropathy patients with wt-Ca and those without wt-CA. Therefore a few parameters are examined. The fourth scale used therefore is the Composite Autonomic Symptom score (COMPASS-31). This scale is a questionnaire with a 31 questions about the complaints in the daily life and also if there complaints/symptoms on the autonomic system. A few questions are asked about different domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal system, bladder, pupillomotor).The total score is minimal 0 and maximal 75 raw counted (100 weighted).Each domain had a weighting factor to be count depending on the answers of the patient.

Secondary outcome: red flags that could increase the awareness of neurologists for wild-type TTR-cardiac amyloidosis

The red flags for wild-type TTR cardiac amyloidosis are among others carpal tunnel syndrome (CTS), wich can be detected by performing an electromyography (EMG).

Secondary outcome: red flags that could increase the awareness of neurologists for wild-type TTR-cardiac amyloidosis

Secondary outcome: red flags that could increase the awareness of neurologists for wild-type TTR-cardiac amyloidosis

Inclusion Criteria: Patients with chronic axonal length-dependent polyneuropathy (CAP) and/or small-fiber neuropathy (SFN) without well-defined etiology. Age: >= 60 years Male and female gender Written informed consent Exclusion Criteria: Known cause of polyneuropathy Other types of peripheral neuropathy than chronic axonal length-dependent polyneuropathy (CAP) and/or small-fiber neuropathy (SFN). Patients younger than 60 years

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