Despite the presence of various signs of cardiac amyloidosis (\"red flags\"), the introduction into routine practice of new non-invasive diagnostic methods (Speckle Tracking technology using echocardiography, myocardial scintigraphy with technetium pyrophosphate, genetic testing, screening for free light chains of immunoglobulins to exclude AL-amyloidosis), which have high specificity and sensitivity, transthyretinic (ATTR) cardiomyopathy is still a difficult to diagnose disease, especially in the early stages when treatment is most effective. The article presents a clinical case of ATTR-amyloidosis with predominant heart damage, manifested by severe diastolic heart failure resistant to treatment. The timing, from the moment of the first episode of decompensation of heart failure to death, is 4 months, which confirms the rapid progression of severe biventricular dysfunction of the heart. Despite the presence of cardiac and extracardial \"red flags\" of ATTR-amyloidosis in the patient, the diagnosis was established at autopsy. The paper analyzes possible errors of early diagnosis at the outpatient and inpatient stages of patient management.
Несмотря на наличие различных признаков амилоидоза сердца («красные флаги»), внедрение в рутинную практику новых неинвазивных методов диагностики (технологии Speckle Tracking с помощью эхокардиографии, сцинтиграфии миокарда с пирофосфатом технеция, генетического тестирования, скрининга на свободные легкие цепи иммуноглобулинов для исключения AL-амилоидоза), которые обладают высокой специфичностью и чувствительностью, транстиретиновая (ATTR) кардиомиопатия все еще остается сложно диагностируемым заболеванием, особенно в ранние сроки, когда лечение является наиболее эффективным. В статье представлен клинический случай ATTR-амилоидоза с преимущественным поражением сердца, проявляющийся тяжелой диастолической сердечной недостаточностью, резистентной к лечению. Сроки от момента 1-го эпизода декомпенсации сердечной недостаточности до смертельного исхода составляют 4 мес, что подтверждает быстрое прогрессирование тяжелой бивентрикулярной дисфункции сердца. Несмотря на наличие у пациента кардиальных и экстракардиальных «красных флагов» ATTR-амилоидоза, диагноз установлен при аутопсии. В работе проанализированы возможные ошибки ранней диагностики на амбулаторном и стационарном этапах ведéния пациента.

UNASSIGNED: Previous literature suggests that patients with transthyretin amyloidosis (ATTR) experience a high burden of ventricular arrhythmias. Despite this evidence, optimal strategies for arrhythmia prevention and treatment remain subject to debate.
UNASSIGNED: We report the case of a patient with hereditary ATTR cardiomyopathy who developed recurrent ventricular tachycardia prior to a decline in his left ventricular ejection fraction (LVEF). Although he ultimately received an intracardiac device (ICD) for secondary prevention of ventricular tachycardia, his clinical course begets the question of whether more aggressive arrhythmia prevention upfront could have prevented his global functional decline.
UNASSIGNED: Given the advent of new disease-modifying therapies for ATTR, it is imperative to reconsider antiarrhythmic strategies in these patients. New decision tools are needed to decide what additional parameters (beyond LVEF ≤ 35%) may warrant ICD placement for primary prevention of ventricular arrhythmias in these patients.

Cardiac amyloidosis is a group of diseases characterized by the deposition of amyloid fibers in cardiac tissue. Two forms are mainly reported: light chain (AL) and transthyretin (ATTR) amyloidosis. Among the complications of transthyretin amyloidosis there are thrombotic events and, to a lesser extent, hemorrhagic events. The latter are likely caused by perivascular amyloid deposition resulting in capillary fragility, in addition to INR lability during anticoagulant therapy. The onset of thrombotic events may be caused by the high prevalence of atrial fibrillation (AF), mechanical cardiac dysfunction and atrial myopathy observed in patients with transthyretin amyloidosis. It remains unclear why thromboembolic events occur even in patients with sinus rhythm or adequate anticoagulation, though a hypercoagulable state or underlying inflammation may be involved. We report a case of cryptogenic ischemic stroke in an 86-year-old woman with transthyretin amyloidosis and sinus rhythm. Traditional coagulation tests, whole blood rotational thromboelastometry and impedance aggregometry did not show a hypercoagulable state. The thrombin generation assay did not reveal a prothrombotic state. However, the study of extracellular vesicles highlighted underlying immune-mediated endothelial damage likely responsible for the thrombotic diathesis. It could be hypothesized that inflammation plays a role in the hypercoagulability of patients with transthyretin amyloidosis. Larger prospective studies are needed to validate our hypothesis.

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant hereditary disorder. In Portugal, it is mainly linked to transthyretin (TTR) mutation, and patients present with length-dependent sensory-motor polyneuropathy, often accompanied by autonomic dysfunction. Treatment options for FAP include liver transplant, and due to the lack of organs, FAP livers began being implanted in patients with severe liver disease in a process known as domino liver transplantation (DLT). We report a case of a 68-year-old Portuguese man, with post-hepatitis C-related cirrhosis liver transplantation, who presented to his family doctor with decreased sensitivity in both feet and weight loss, which were initially attributed to diabetic neuropathy and an adjustment in diabetic medication, respectively. Symptoms evolved to changes in both feet\'s thermal and painful sensitivity, reduced sensitivity in both hands, diarrhea, and progressive weight loss. At this time, the patient\'s disclosure of receiving a DLT prompted the correct diagnosis of iatrogenic amyloid polyneuropathy. This case underscores the challenges in diagnosing and managing iatrogenic amyloid polyneuropathy following DLT, highlighting the importance of prompt identification of DLT recipients, active vigilance of these patients via structured monitoring, and increased healthcare providers\' awareness of this practice so that early signs of the disease may be recognized.

We report a 73-year-old woman who started developing recurrent transient aphasia at the age of 66 years. During the attacks, she was aware she could not understand what was being said and both her spoken and written speech were meaningless. The attacks usually lasted for a few days, following which she could explain what had happened. Anti-epileptics did not improve her symptoms. She also noticed tremor of her right hand and gait disturbance at the age of 71 years. The recurrent transient aphasia was followed by drop attacks. At the time of her admission to our hospital, she showed paraplegia, phonological paraphasia, and difficulty in understanding complex sentences. Her language disturbance resembled a logopenic variant of primary progressive aphasia. However, the symptoms fluctuated for a few days and subsequently improved. Electroencephalography showed no abnormalities. Gadolinium-enhanced brain and spinal MRI showed diffuse leptomeningeal enhancement over the surface of the spinal cord, brain stem, and cerebrum on T1-weighed imaging. Surgical biopsy of a varicose vein in the subarachnoid space at the level of the Th11 spinal cord was performed. Pathological evaluation of the biopsied specimens revealed TTR-immunolabeled amyloid deposits in the subarachnoid vessel walls and on the arachnoid membrane. Gene analysis revealed c.265T>C, p.Y89H (Y69H) TTR mutation, which is known as one of the causative mutations of familial leptomeningeal amyloidosis. Leptomeningeal forms of transthyretin amyloidosis might present transient focal neurological episodes.

UNASSIGNED: This case emphasizes the significance of cardiac amyloidosis as a potential diagnosis in individuals manifesting with lesion-free pruritus and normal liver tests.
UNASSIGNED: Amyloidosis is a complex disorder in which misfolded proteins accumulate in various organs of the body. Cardiac amyloidosis (CA) can lead to heart failure, cardiac arrhythmia, sudden cardiac death, and deposition of proteins in coronary arteries. Diagnosing CA can be difficult, as the cardiac manifestations of amyloidosis can be similar to more prevalent etiologies. In addition, the accumulation of proteins in soft tissues, including the skin, can cause pruritus. In this paper, we present a 70-year-old man with generalized pruritus and no skin lesions, later diagnosed as CA after detecting ascites fluid. This case underscores the importance of considering amyloidosis in patients presenting with nonspecific symptoms, particularly those affecting the skin, and highlights the need for increased awareness of this disease among clinicians.

Cardiac amyloidosis is a condition that results from the accumulation of amyloid proteins in the extracellular matrix of the myocardium. The diagnosis of this disease was challenging as it lacked distinct clinical symptoms and required a biopsy to confirm amyloid deposition. However, there is increasing evidence of non-invasive diagnostic criteria for cardiac amyloidosis, especially for the transthyretin (TTR) type. We report a case of a patient with both cardiac transthyretin amyloidosis (ATTR) and Paget\'s disease, and we highlight the various radiological features of these two conditions using hybrid imaging techniques. In addition, we discuss the diagnostic imaging characteristics of ATTR cardiac amyloidosis.

Restrictive cardiomyopathy secondary to cardiac amyloidosis is an underdiagnosed cause of heart failure and it is associated with significant morbidity and mortality. The most common types of amyloidosis are light chain amyloidosis, transthyretin amyloidosis and secondary amyloidosis. We report the case of a 84-year-old man that presented with new onset signs and symptoms of heart failure. Multimodality imaging with echocardiogram and bone tracer cardiac scintigraphy along with biomarkers, monoclonal proteins analysis and genetic test allowed to diagnosed a wild-type transthyretin amyloidosis. We discuss the clinical and diagnostic features and review the current literature about cardiac amyloidosis. This paper aims to increase clinicians\' awareness of cardiac amyloidosis to promptly recognize, diagnose and treat it.

A 31-year-old woman with transthyretin (TTR) amyloidosis secondary to a Thr60Ala mutation developed recurrent stroke-like episodes with fluctuating mental status. Evaluation for stroke and seizures was unrevealing. She was found to have leptomeningeal contrast enhancement on magnetic resonance imaging, which was confirmed to be CNS TTR amyloidosis on histopathology following brain and dura biopsy. While leptomeningeal disease has rarely been known to be associated with TTR amyloidosis, this is the first documented case of leptomeningeal disease secondary to a Thr60Ala mutation in the TTR gene. A literature review of TTR amyloidosis is presented with special focus on the treatment of leptomeningeal TTR amyloidosis.

Familial amyloid polyneuropathy (PN), also known as amyloid transthyretin (TTR)-PN is an autosomal dominant adult-onset fatal disease, if not treated. It occurs due to mutations in (TTR) gene which leads to a faulty TTR protein which folds up to form amyloid and gets deposited mainly on nerves and causes length-dependent PN and autonomic dysfunction. We report a case of a 45-year-old female who presented with symptoms of painful peripheral neuropathy for 5 months, a history of deafness for 5 years, and cardiac pacemaker implantation 2 years ago for complete heart block. She denied any symptoms of autonomic dysfunction. Her brother with similar symptoms died of cardiac arrest at the age of 50 years. Clinical examination was suggestive of symmetrical sensorimotor PN. The nerve conduction study was suggestive of axonal sensorimotor PN. Abdominal fat biopsy was negative for amyloid. Sural nerve biopsy was suggestive of amyloid neuropathy. Genetic analysis showed c. 165G > T mutation encoding amino acid p. Lys55Asn on exon-4 of TTR gene. This mutation has not been reported from India.
Résumé La polyneuropathie amyloïde familiale (NP), également connue sous le nom de transthyrétine amyloïde (TTR) -PN, est une maladie mortelle autosomique dominante de l\'adulte, si elle n\'est pas traitée. Il se produit en raison de mutations du gène (TTR) qui conduisent à une protéine TTR défectueuse qui se replie pour former de l\'amyloïde et se dépose principalement sur les nerfs et provoque une PN dépendante de la longueur et un dysfonctionnement autonome. Nous rapportons le cas d\'une femme de 45 ans qui présentait des symptômes de neuropathie périphérique douloureuse depuis 5 mois, des antécédents de surdité depuis 5 ans et l\'implantation d\'un stimulateur cardiaque il y a 2 ans pour un bloc cardiaque complet. Elle a nié tout symptôme de dysfonctionnement autonome. Son frère présentant des symptômes similaires est décédé d\'un arrêt cardiaque à l\'âge de 50 ans. L\'examen clinique évoquait une NP sensorimotrice symétrique. L\'étude de la conduction nerveuse était évocatrice d\'une NP sensorimotrice axonale. La biopsie de la graisse abdominale était négative pour l\'amyloïde. La biopsie du nerf sural était évocatrice d\'une neuropathie amyloïde. L\'analyse génétique a montré c. Mutation 165G > T codant pour l\'acide aminé p. Lys55Asn sur l\'exon-4 du gène TTR. Cette mutation n\'a pas été signalée en Inde. Mots clés: Neuropathie amyloïde familiale, tests génétiques, biopsie nerveuse, amylose à transthyrétine.