Heart failure in amyloidotic cardiomyopathy: a hemodynamic study of the three main etiologies.

Introduzione. Lo scompenso cardiaco (HF) rappresenta una delle principali manifestazioni cliniche dell’amiloidosi cardiaca (AC) e ha importanti implicazioni prognostiche. Tuttavia, pochi studi fisiopatologici riguardanti HF in AC hanno valutato l’aspetto emodinamico. Abbiamo pertanto analizzato HF nelle tre principali forme eziologiche di AC: AL (amiloidosi sistemica primitiva), m-ATTR (amiloidosi familiare TTR-relata) e wt-ATTR (amiloidosi senile). Metodi. Fra i 340 pazienti con diagnosi di AC (145 AL, 119 m-ATTR, 76 wt-ATTR) seguiti presso il nostro Centro tra 1990-2015, abbiamo analizzato gli aspetti clinici, strumentali e prognostici di quelli in classe NYHA III-IV alla diagnosi. Risultati. 96 (28%) hanno mostrato segni e sintomi di HF (52 AL, 22 m-ATTR, 22 wt-ATTR). All’ecocardiogramma il valore di frazione d’eiezione del ventricolo sinistro (LVEF) era compreso fra il 22 e il 67% ed era <50% in 54 pazienti (52%). Al cateterismo cardiaco destro, in più del 70% dei pazienti è stata documentata una pressione d’incuneamento polmonare (PCWP) aumentata e un ridotto indice cardiaco (CI). Inoltre, nel 45% dei casi sono stati riscontrati una ridotta LVEF e un’aumentata PCWP, mentre nel 30% i valori di LVEF sono risultati normali con PCWP aumentata. 10 pazienti mostravano normale LVEF e PCWP pur in presenza di HF. Durante il follow-up 66 (27%) hanno sviluppato segni e sintomi di HF (6.2% person/years). I pazienti con HF alla presentazione avevano una sopravvivenza inferiore rispetto a quelli in buon compenso. L’eziologia AL e il valore di CI erano predittori indipendenti di mortalità nei pazienti in classe NYHA III-IV alla presentazione. Conclusione. HF è presente nel 30% dei pazienti alla prima osservazione e non è solo dovuto ad una disfunzione diastolica “pura”, isolata, ma ad un eterogeneo range di disfunzione diastolica e sistolica. HF alla presentazione condiziona la prognosi dei pazienti. Inoltre, l’eziologia AL e CI ridotto rappresentano variabili indipendenti di mortalità.Introduction. In amyloidotic cardiomyopathy (AC), heart failure (HF) is one of the main clinical manifestations. However, a precise pathophysiological and prognostic characterization of HF in this condition is not available. We assessed the clinical and instrumental profile and outcome of patients with advanced HF (i.e. NYHA class III-IV) at the time of first evaluation in light-chain (AL), hereditary transthyretin-related (m-ATTR) and non-mutant transthyretin-related (wt-ATTR) AC. Methods. We analysed the 340 patients diagnosed with AC (145 AL, 119 m-ATTR, 76 wt-ATTR) at our Centre between 1990 and 2015. We evaluated clinical, ECG, echocardiographic and hemodynamic profiles as well as survival data of those with advanced HF at time of diagnosis. Results. 96 (28%) patients presented advanced HF at first evaluation (52 AL, 22 m-ATTR, 22 wt-ATTR). Left ventricle ejection fraction (LVEF) ranged between 22 and 67% and was <50% in 54 patients (52%). Increased pulmonary capillary wedge pressure (PCWP) and reduced cardiac index (CI) were documented in more than 70%. 45% of patients showed reduced LVEF with increased PCWP, while in about 1/3 of cases a normal LVEF and increased PCWP were present. 10 patients with HF at presentation had normal LVEF and PCWP. During follow-up 66 (27%) developed HF: 29 AL, 23 wt-ATTR, 14 m-ATTR with incidence rate of 6.2% person/years. Survival was reduced in patients with HF both in overall population and in three main subgroups. AL AC and reduced CI were independent predictors of mortality in patients in NYHA class III-IV at presentation. Conclusion. In 30% of AC patients, HF is one of main manifestation at first evaluation. The pathophysiological substrate of HF in these patients is systolic and/or diastolic dysfunction. Survival was reduced in AC patients with HF at presentation. AL etiology and CI were indipendent predictors of outcome

Gêneros de texto/discurso e os desafios da contemporaneidade

NASCIMENTO, Elvira Lopes; ROJO, Roxane Helena Rodrigues (org.).Gêneros de texto/discurso e os desafios da contemporaneidade.Campinas, São Paulo: Pontes, 2014, 369p

Primary Sjögren's syndrome in children: Is a family approach indicated?

[No abstract available

Neem oil nanoemulsions: characterisation and antioxidant activity

The aim of the present work is to develop nanoemulsions (NEs), nanosized emulsions, manufactured for improving the delivery of active pharmaceutical ingredients. In particular, nanoemulsions composed of Neem seed oil, contain rich bioactive components, and Tween 20 as nonionic surfactant were prepared. A mean droplet size ranging from 10 to 100nm was obtained by modulating the oil/surfactant ratio. Physicochemical characterisation was carried out evaluating size, f-potential, microviscosity, polarity and turbidity of the external shell and morphology, along with stability in simulated cerebrospinal fluid (CSF), activity of Neem oil alone and in NEs, HEp-2 cell interaction and cytotoxicity studies. This study confirms the formation of NEs by Tween 20 and Neem oil at different weight ratios with small and homogenous dimensions. The antioxidant activity of Neem oil alone and in NEs was comparable, whereas its cytotoxicity was strongly reduced when loaded in NEs after interaction with HEp-2 cells

Insights into the Structures of Bilirubin and Biliverdin from Vibrational and Electronic Circular Dichroism: History and Perspectives

: In this work we review research activities on a few of the most relevant structural aspects of bilirubin (BR) and biliverdin (BV). Special attention is paid to the exocyclic C=C bonds being in mostly Z rather than E configurations, and to the overall conformation being essentially different for BR and BV due to the presence or absence of the double C=C bond at C-10. In both cases, racemic mixtures of each compound of either M or P configuration are present in achiral solutions; however, imbalance between the two configurations may be easily achieved. In particular, results based on chiroptical spectroscopies, both electronic and vibrational circular dichroism (ECD and VCD) methods, are presented for chirally derivatized BR and BV molecules. Finally, we review deracemization experiments monitored with ECD data from our lab for BR in the presence of serum albumin and anesthetic compounds

Cardiac amyloidosis: the great pretender

Cardiac amyloidosis (CA) is often misdiagnosed because of both physician-related and disease-related reasons including: fragmented knowledge among different specialties and subspecialties, shortage of centres and specialists dedicated to disease management, erroneous belief it is an incurable disease, rarity of the condition, intrinsic phenotypic heterogeneity, genotypic heterogeneity in transthyretin-related forms and the necessity of target organ tissue histological diagnosis in the vast majority of cases. Pitfalls, incorrect beliefs and deceits challenge not only the path to the diagnosis of CA but also the precise identification of aetiological subtype. The awareness of this condition is the most important prerequisite for the management of the risk of underdiagnoses and misdiagnosis. Almost all clinical, imaging and laboratory tests can be misinterpreted, but fortunately each of these diagnostic steps can also offer diagnostic “red flags” (i.e. highly suggestive findings that can foster the correct diagnostic suspicion and facilitate early, timely diagnosis). This is especially important because outcomes in CA are largely driven by the severity of cardiac dysfunction and emerging therapies are aimed at preventing further amyloid deposition

Nuclear imaging for cardiac amyloidosis

Histological analysis of endomyocardial tissue is still the gold standard for the diagnosis of cardiac amyloidosis, but has its limitations. Accordingly, there is a need for non-invasive modalities to diagnose cardiac amyloidosis. Echocardiography and ultrasound and magnetic resonance imaging can show characteristics which may not be very specific for cardiac amyloid. Nuclear medicine has gained a precise role in this context: several imaging modalities have become available for the diagnosis and prognostic stratification of cardiac amyloidosis during the last two decades. The different classes of radiopharmaceuticals have the potential to bind different constituents of the amyloidotic infiltrates, with some relevant differences among the various aetiologic types of amyloidosis and the different organs and tissues involved. This review focuses on the background of the commonly used modalities, their present clinical applications, and future clinical perspectives in imaging patients with (suspected) cardiac amyloidosis. The main focus is on conventional nuclear medicine (bone scintigraphy, cardiac sympathetic innervation) and positron emission tomography

Amyloidosis: What does pathology offer? The evolving field of tissue biopsy

Since the mid-nineteenth century pathology has followed the convoluted story of amyloidosis, recognized its morphology in tissues and made identification possible using specific staining. Since then, pathology studies have made a significant contribution and advanced knowledge of the disease, so providing valuable information on the pathophysiology of amyloid aggregation and opening the way to clinical studies and non-invasive diagnostic techniques. As amyloidosis is a heterogeneous disease with various organ and tissue deposition patterns, histology evaluation, far from offering a simple yes/no indication of amyloid presence, can provide a wide spectrum of qualitative and quantitative information related to and changing with the etiology of the disease, the comorbidities and the clinical characteristics of patients. With the exception of cardiac transthyretin related amyloidosis cases, which today can be diagnosed using non-biopsy algorithms when stringent clinical criteria are met, tissue biopsy is still an essential tool for a definitive diagnosis in doubtful cases and also to define etiology by typing amyloid fibrils. This review describes the histologic approach to amyloidosis today and the current role of tissue screening biopsy or targeted organ biopsy protocols in the light of present diagnostic algorithms and various clinical situations, with particular focus on endomyocardial and renal biopsies. Special attention is given to techniques for typing amyloid fibril proteins, necessary for the new therapies available today for cardiac transthyretin related amyloidosis and to avoid patients receiving inappropriate chemotherapy in presence of plasma cell dyscrasia unrelated to amyloidosis. As the disease is still burdened with high mortality, the role of tissue biopsy in early diagnosis to assure prompt treatment is also mentioned