Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009-2019).

OBJECTIVE: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg. METHODS: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance. RESULTS: Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients. CONCLUSION: In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.

Upper limb onset of hereditary transthyretin amyloidosis is common in non-endemic areas.

BACKGROUND AND PURPOSE: The aim is to describe an uncommon phenotype of hereditary ATTR neuropathy with upper limb onset. METHODS: The French TTR Familial Amyloid Polyneuropathy database was used for a retrospective evaluation of 32 consecutive patients with upper limb onset of the neuropathy (study group) and they were compared to 31 Portuguese early-onset patients and 99 late-onset patients without upper limb onset. RESULTS: Initial upper limb symptoms were mostly sensory. Lower limb symptoms began 2.3 ± 3 years after upper limb symptoms. Twenty-four (75%) patients were initially misdiagnosed, with 15 different diagnoses. More patients in the study group had a Neuropathy Impairment Score upper limb/lower limb ratio > 1 compared to the late-onset patient group. The study group had significantly more pronounced axonal loss in the median and ulnar motor nerves and the ulnar sensory and sural nerves. On radial nerve biopsies (n = 11), epineurial vessels were abnormal in six cases, including amyloid deposits in vessel walls (3/11), with vessel occlusion in two cases. CONCLUSION: Upper limb onset of hereditary ATTR neuropathy is not rare in non-endemic areas. It is important to propose early TTR sequencing of patients with idiopathic upper limb neuropathies, as specific management and treatment are required.

Multimodality Imaging of Cardiac Transthyretin Amyloidosis 16 Years After a Domino Liver Transplantation.

We report the case of a 62-year-old man hospitalized in May 2015 for symptomatic heart failure. His medical history included two liver transplantations. The first liver transplantation was performed in 1999 for a mixed alcoholic and hepatitis C-related cirrhosis and the patient received the liver of another patient with Val30Met transthyretin amyloidosis using the domino technique. In 2008, he complained of neuropathic pains and an iatrogenic-acquired transthyretin amyloidosis was diagnosed. On cardiac evaluation, amyloidosis was suspected. In March 2010, a second liver transplantation was performed with a deceased donor without complication. In May 2015, a first episode of symptomatic heart failure occurred and cardiac amyloidosis was investigated by a multimodality evaluation. Electrocardiogram, cardiac biomarkers, echocardiography, and cardiac MRI were in favor of the diagnosis of amyloidosis, whereas 99m Tc-dicarboxypropane diphosphonate scintigraphy was not. Endomyocardial biopsy finally confirmed the positive diagnosis of iatrogenic-acquired cardiac amyloidosis. This case is, to the best of our knowledge, the first to report biopsy-proven cardiac amyloidosis induced by domino liver transplantation and progressing heart failure in spite of retransplantation. The diagnostic modalities are discussed. This case should alert physicians to the cardiac risk in domino liver transplanted patients.

[Multidetector computed tomography coronarography: from studies to everyday life]. / Le scanner coronaire : des études à la pratique courante.

INTRODUCTION: Multidetector computed tomography coronarography is a promising tool, offering a non-invasive anatomic evaluation of coronary arteries. The great majority of studies conducted upon it are single-center studies, and have reported results based upon a highly selected patient population. Our aim was to determine its diagnostic accuracy among an unselected population in multicenter studies. METHODS: Fifty-two patients were included in a non-randomised, retrospective study. Patients underwent multidetector computed tomography coronarography (16, 40 and 64 slices), in ten different centers (community hospitals or private centres), for clinical suspicion of coronary stenoses. The diagnostic accuracy for detecting significant coronary stenoses (> or =50%) was determined in comparison with conventional coronarography. RESULTS: The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy were 91.4%, 17.7%, 69.6%, 50.0%, and 67.3%, respectively, in a patient-based analysis, and 55.3%, 85.6%, 30.3%, 94.4% and 82.5% in a segment-based analysis. CONCLUSION: The results of this study indicate that routine implementation of multidetector computed tomography coronarography is limited by a high false-positive rate, when performed among an unselected population of patients with a high pretest probability of having coronary stenoses, in centres with variable expertises. Its place within the range of diagnostic tools has yet to be determined by large multicenter studies, before being subject to precise recommendations framing its routine clinical application.