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A 74-year-old woman with a history of diastolic heart failure and refractory atrial fibrillation (AF) presented with unstable angina for coronary artery bypass grafting. Routine pathological analysis of tissue specimens obtained from the left atrial appendage revealed subendocardial and interstitial fibrosis and patchy amyloid deposits with Congo red staining demonstrating filamentous deposits. Mass spectrometry was consistent with isolated atrial amyloidosis (IAA). IAA in this patient was found incidentally on routine postoperative pathology, but likely contributed to significant morbidity. The established relationship between IAA with AF and diastolic heart failure underscores the relevance. Further delineating the pathogenesis has potentially immense implications for the future management of associated conditions. To bridge the gaps in the understanding, a standardised approach to diagnosis is needed to open the door to a large-scale study and further work toward establishing evidence-based management pathways.

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are very common conditions, particularly in the elderly. However, the mechanisms underlying the two disorders, including their intricate interaction have not been fully resolved. Here, our aim is to review the evidence on the role of the two types of senile amyloidosis in this connection. Two types of senile amyloidosis can be identified: wild-type transthyretin (TTR)-derived amyloidosis (ATTRwt) and isolated atrial amyloidosis (IAA). ATTRwt is an underlying condition that is being increasingly recognized in patients with HFpEF and often accompanied by AF. IAA is an established cause of AF, adding to the mechanism problem. New diagnostic and therapeutic possibilities have emerged that may facilitate clinical management of (senile) amyloidosis, which in turn may have implications for the management of HFpEF and AF.

OBJECTIVESDiffuse cardiac amyloidosis is a significant diagnosis with a poor prognosis. Isolated atrial amyloidosis (IAA) is the most common form of cardiac amyloidosis caused by accumulation of alpha-atrial natriuretic peptide. IAA has been associated with dysrhythmia, but otherwise remains a poorly characterized condition. The impact of incidental IAA on postoperative outcome following cardiac surgery has not previously been reported. The purpose of this study was to examine the impact of isolated atrial amyloid on patient outcomes following cardiac surgery.methodsA retrospective analysis was performed of all patients having excision of the left atrial appendage during cardiac surgery at our centre over a 5-year period. Patients with histological evidence of IAA were compared to patients without this diagnosis. IAA was diagnosed by immunohistochemistry for atrial natriuretic peptide.RESULTSA total of 167 patients underwent left atrial appendage excision and of these 26 (15.6%) were found to have IAA. Preoperative characteristics were similar between the 2 groups. A significantly greater proportion of patients with IAA experienced dysrhythmia requiring implantation of a permanent pacemaker (23.1% vs 7.8%, P = 0.03). There was also a significantly elevated incidence of perioperative death in the IAA group (11.5% vs 1.4%, P = 0.03) and inferior 1-year survival (84.6% vs 96.5%, P = 0.02).CONCLUSIONSThe presence of IAA may be associated with inferior outcomes following cardiac surgery, with increased morbidity in the early postoperative period and inferior long-term survival. Knowledge of the diagnosis preoperatively may facilitate management of patients.

Telocytes are interstitial cells with long, thin processes by which they contact each other and form a network in the interstitium. Myocardial remodeling of adult patients with different forms of atrial fibrillation (AF) occurs with an increase in fibrosis, age-related isolated atrial amyloidosis (IAA), cardiomyocyte hypertrophy and myolysis. This study aimed to determine the ultrastructural and immunohistochemical features of cardiac telocytes in patients with AF and AF + IAA. IAA associated with accumulation of atrial natriuretic factor was detected in 4.3–25% biopsies of left (LAA) and 21.7–41.7% of right (RAA) atrial appendage myocardium. Telocytes were identified at ultrastructural level more often in AF + IAA, than in AF group and correlated with AF duration and mitral valve regurgitation. Telocytes had ultrastructural signs of synthetic, proliferative, and phagocytic activity. Telocytes corresponded to CD117+, vimentin+, CD34+, CD44+, CD68+, CD16+, S100-, CD105- immunophenotype. No significant differences in telocytes morphology and immunophenotype were found in patients with various forms of AF. CD68-positive cells were detected more often in AF + IAA than AF group. We assume that in aged AF + IAA patients remodeling of atrial myocardium provoked transformation of telocytes into “transitional forms” combining the morphological and immunohistochemical features with signs of fibroblast-, histiocyte- and endotheliocyte-like cells.

Atrial fibrillation(AF) is as an abnormal irregular rhythm with chaotic generation of electrical signals in the atria of the heart. Various studies in the West have proved that atrial substrates, like isolated atrial amyloidosis can trigger the development of atrial fibrillation. In India, these structural changes have been analyzed on autopsied hearts.To determine the role of Atrial Amyloid as a substrate for Atrial fibrillation in ante mortem hearts.Atrial appendages were obtained from seventy five patients undergoing open heart surgery at a tertiary care hospital in south India. They were stained with HematoxylinEosin, Masson's Trichrome and Congo red stains and were examined for myocarditis, fibrosis and amyloidosis, respectively. 30 (40%) patients were in AF. Amyloid deposits were seen in 3 cases. All the three were in AF and had undergone mitral valve replacement (MVR) (P0.05). 2 out of the 3 amyloid-positive cases showed active myocarditis and severe scarring but there was no statistically significant correlation between these factors.Amyloid and myocarditis, independently act as an arrythmogenic substrates in the development of atrial fibrillation and are also increasingly associated with female gender and MVR. We hypothesize that the amyloid deposits are due to isolated atrial amyloidosis as they were seen only in young individuals. Some patients in sinus rhythm (SR) had large left atria and myocarditis and probably are at a higher risk for developing AF. Hence, follow-up of these patients is required for prevention of severe organ damage and timely therapeutic intervention.

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are very common conditions, particularly in the elderly. However, the mechanisms underlying the two disorders, including their intricate interaction have not been fully resolved. Here, our aim is to review the evidence on the role of the two types of senile amyloidosis in this connection. Two types of senile amyloidosis can be identified: wild-type transthyretin (TTR)-derived amyloidosis (ATTRwt) and isolated atrial amyloidosis (IAA). ATTRwt is an underlying condition that is being increasingly recognized in patients with HFpEF and often accompanied by AF. IAA is an established cause of AF, adding to the mechanism problem. New diagnostic and therapeutic possibilities have emerged that may facilitate clinical management of (senile) amyloidosis, which in turn may have implications for the management of HFpEF and AF.

to analyze the morphological features of the myocardium of the atrial appendages in patients with different forms of atrial fibrillation (AF) and to compare the findings with the clinical parameters of patients.Light and electron microscopies were used to examine the myocardium of the atrial appendages in adult patients with paroxysmal (PAF), persistent (PrAF), or long-standing persistent atrial fibrillation (LPAF) and in comparison group patients with sinus rhythm without history of AF. A morphometric method was employed to evaluate myocardial fibrosis and to measure the diameter of cardiomyocytes (CMCs); the degree of lipomatosis and amyloidosis was semiquantitatively determined; and the content of CMC myofibrils was estimated. Atrial natriuretic peptide content in the myocytes was measured by immunoconfocal microscopy.In all groups, the patients with AF were found to have signs of atrial structural remodeling: fibrosis, lipomatosis, isolated atrial amyloidosis, CMC hypertrophy with the phenomena of a partial loss of myofibrils without significant differences between these parameters in different groups. In PAF patients, atrial remodeling was accompanied by hypertrophy of a number of CMCs with their higher myofibrilar mass; the increased CMC size in the left atrial appendage prevented left atrial enlargement; the degree of amyloidosis negatively correlated with the CMC myofibrillar loss that was recorded in the minor CMCs; the degree of CMC myolysis positively correlated with mitral valve insufficiency and left atrial enlargement. In contrast to the clinical and morphological changes that are typical of PAF, in LPAF the increase in CMC sizes was positively correlated with left atrial enlargement and mitral annular dilatation; while the myofibrillar loss phenomenon was noted in the most hypertrophied CMCs; the degree of amyloidosis was positively correlated with CMC myofibrillar loss. In the patients with PrAF, the size of CMCs did not correlate with their myofibril content.The patients with PAF were ascertained to have opposite changes in the ratio of CMC hypertrophy to left atrial enlargement, amyloidosis, and CMC myofibrillar loss, hypertrophy of CMCs and their myofibril content in comparison with these indicators in LPAF.Цель исследования - анализ морфологических особенностей миокарда ушек предсердий у пациентов с разными формами фибрилляции предсердий (ФП) и сопоставление полученных данных с клиническими параметрами пациентов. Материал и методы. Методами световой и электронной микроскопии исследован миокард ушек предсердий взрослых пациентов с пароксизмальной (ПФП), персистирующей (ПРФП) и длительно персистирующей фибрилляцией предсердий (ДПФП) и пациентов группы сравнения с синусовым ритмом без ФП в анамнезе. Методом морфометрии оценивали фиброз миокарда, измеряли диаметр кардиомиоцитов (КМЦ), полуколичественно определяли выраженность липоматоза, амилоидоза и оценивали содержание миофибрилл в КМЦ. Методом иммуноконфокальной микроскопии в миоцитах определяли содержание предсердного натрийуретического пептида. Результаты. У пациентов всех групп с ФП обнаружены признаки структурного ремоделирования миокарда предсердий: фиброз, липоматоз, изолированный амилоидоз предсердий, гипертрофия КМЦ с явлениями частичной утраты миофибрилл без достоверных различий между этими параметрами в разных группах. У пациентов с ПФП перестройка миокарда предсердий сопровождалась гипертрофией части КМЦ с увеличением в них массы миофибрилл; увеличение размера КМЦ ушка левого предсердия предотвращало дилатацию левого предсердия; выраженность амилоидоза отрицательно коррелировала с утратой миофибрилл, которую регистрировали в мелких КМЦ, степень миолиза КМЦ положительно коррелировала с недостаточностью митрального клапана и дилатацией левого предсердия. В противоположность клинико-морфологическим изменениям, характерным для ПФП, при ДПФП увеличение размера КМЦ положительно коррелировало с дилатацией левого предсердия и фиброзного кольца митрального клапана, феномен утраты миофибрилл при этом отмечен в наиболее гипертрофированных КМЦ, выраженность амилоидоза положительно коррелировала с утратой миофибрилл в КМЦ. У пациентов с ПРФП не обнаружено взаимосвязи размера КМЦ и содержания в них миофибрилл. Заключение. У пациентов с ПФП выявлены противоположные изменения в соотношении гипертрофии КМЦ и дилатации левого предсердия, амилоидоза и утраты миофибрилл в КМЦ, гипертрофии КМЦ и утраты в них миофибрилл по сравнению с этими показателями при ДПФП.

Telocytes, a recently discovered type of interstitial cells, have a very distinctive morphology - the small cell body with long extensions, named telopodes. In our review, apart from introducing general aspects of telocytes, we focus on properties, functions and future potential of those cells in cardiovascular system. However, physiological functions of telocytes in cardiovascular system are still regarded as quite enigmatic. Previous studies claim that they play a role in organogenesis and regeneration, bioelectrical signalling, mechanoelectrical coupling, anti-oxidative protection, angiogenesis and regulation of blood flow. As well, they are presumably connected with the presence of blood-myocardium barrier and proper organisation of extracellular matrix. Moreover, there exists a significant link between the quantity of telocytes in tissue and numerous cardiovascular diseases such as: myocardial infarction, cardiomyopathies, systemic sclerosis, heart failure, atrial fibrillation, isolated atrial amyloidosis, myxomatous valve degeneration and hyperplastic consequences of vascular injury. Thanks to their unique properties, telocytes might be a breakthrough in treatment of cardiovascular diseases, as they may be effective in reversing effects of myocardial infarction. Telocytes also may play a major role in tissue engineering - they might be the key factor in creating stable and efficient vascular network in larger synthetic tissues or organs (Tab. 1, Fig. 3, Ref. 53).