Galina F Makhaeva, Nadezhda V Kovaleva, Elena V Rudakova, Natalia P Boltneva, Sofya V Lushchekina, Irina I Faingold, Darya A Poletaeva, Yuliya V Soldatova, Raisa A Kotelnikova, Igor V Serkov, Anatoly K Ustinov, Alexey N Proshin, Eugene V Radchenko, Vladimir A Palyulin, Rudy J Richardson
New hybrids of 4-amino-2,3-polymethylenequinoline with different sizes of the aliphatic ring linked to butylated hydroxytoluene (BHT) by enaminoalkyl ( 7 ) or aminoalkyl ( 8 ) spacers were synthesized as potential multifunctional agents for Alzheimer's disease (AD) treatment. All compounds were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity toward BChE. Lead compound 8c , 2,6-di- tert -butyl-4-{[2-(7,8,9,10- tetrahydro-6H-cyclohepta[b]quinolin-11-ylamino)-ethylimino]-methyl}-phenol exhibited an IC50 (AChE) = 1...
December 12, 2020: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Massimo Russo, Luca Gentile, Antonio Toscano, M'Hammed Aguennouz, Giuseppe Vita, Anna Mazzeo
Hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy is a progressive disease that is transmitted as an autosomal dominant trait and characterized by multiple organ failure, including axonal sensory-motor neuropathy, cardiac involvement, and autonomic dysfunction. Liver transplantation (LT) and combined heart-liver transplantation, introduced in the 1990s, have been the only therapies for almost two decades. In 2011, tafamidis meglumine became the first specific drug approved by regulatory agencies, since then the attention toward this disease has progressively increased and several drugs with different mechanisms of action are now available...
December 9, 2020: Brain Sciences
Reina Tsuda, Koichiro Shinoda, Ryuichi Ushijima, Makiko Nakamura, Nagaaki Katoh, Johji Imura, Kazuyuki Tobe
A 72-year-old woman was diagnosed with rheumatoid arthritis (RA) 6 years ago and was referred to our hospital for the management of RA. She achieved remission with methotrexate, and her arthritis was well-controlled. Two years ago, a routine, preoperative check-up revealed left ventricular hypertrophy. One month before the current admission, she experienced worsening heart failure, and echocardiography and other findings suggested cardiac amyloidosis as the underlying cause. She was then admitted to our hospital...
December 14, 2020: Modern rheumatology case reports
Mohamad Omar Choukair, Ahmad Halawi, Amal Nehmeh, Hasan Kazma
Amyloid light-chain (AL) amyloidosis is a rare disease with a broad clinical presentation that depends on the affected organ. Cardiac amyloidosis, a rare entity, can present as an isolated form of AL amyloidosis. This isolated form is considered a challenging diagnosis due to its broad nonspecific clinical presentation. In this article, we report a case of an adult male who presented with shortness of breath and was found to have many specific features of cardiac amyloidosis on echocardiography. In absence of other organ involvement, the results of the echocardiography directed us toward the diagnosis of AL cardiac amyloidosis...
November 8, 2020: Curēus
Michelle C Johansen, Thomas H Mosley, David S Knopman, Dean F Wong, Chiadi Ndumele, Amil M Shah, Scott D Solomon, Rebecca F Gottesman
Background Atrial fibrillation (AF) is a risk factor for cognitive decline, possibly from silent brain infarction. Left atrial changes in structure or function (atrial cardiopathy) can lead to AF but may impact cognition independently. It is unknown if AF or atrial cardiopathy also acts on Alzheimer disease-specific mechanisms, such as deposition of β-amyloid. Methods and Results A total of 316 dementia-free participants from the ARIC (Atherosclerosis Risk in Communities) study underwent florbetapir positron emission tomography, electrocardiography, and 2-dimensional echocardiography...
December 8, 2020: Journal of the American Heart Association
Matthias N Ungerer, Ernst Hund, Jan C Purrucker, Laura Huber, Christoph Kimmich, Fabian Aus dem Siepen, Selina Hein, Arnt V Kristen, Katrin Hinderhofer, Jennifer Kollmer, Stefan Schönland, Ute Hegenbart, Markus Weiler
BACKGROUND: Hereditary transthyretin amyloidosis is caused by pathogenic variants in the TTR gene and typically manifests, alongside cardiac and other organ dysfunctions, with a rapidly progressive sensorimotor and autonomic polyneuropathy (ATTRv-PN) leading to severe disability. While most prospective studies have focussed on endemic ATTRv-PN, real-world data on non-endemic, mostly late-onset ATTRv-PN are limited. METHODS: This retrospective study investigated ATTRv-PN patients treated at the Amyloidosis Centre of Heidelberg University Hospital between November 1999 and July 2020...
December 7, 2020: Amyloid: the International Journal of Experimental and Clinical Investigation
Renier A B Visser, Céline Gravenor, Sennia Ahmed, Amer Harky
Systemic amyloidosis is caused by the deposition of amyloid proteins in varying organ systems throughout the body, leading to dysfunction within those systems. The development of cardiac amyloidosis is one of the main indicators of poor prognosis in patients. Cardiac amyloidosis is most commonly caused by the immunoglobulin light chain amyloidosis and the transthyretin amyloidosis. Both have poor prognoses when associated with cardiac amyloidosis; however, the patients with the former subtype fair far worse than those with the latter...
December 6, 2020: Journal of Cardiac Surgery
Oreoluwa Oladiran, Adeolu Oladunjoye, Olubunmi O Oladunjoye, Anish Paudel, Ibiyemi Oke, Lisa Motz, Sarah Luber, Anthony Licata
BACKGROUND Cardiac amyloidosis is an infiltrative cardiomyopathy caused by the extracellular deposition of insoluble precursor protein amyloid fibrils. These depositions of protein amyloid fibrils are found on the atria and ventricles and can cause a wide array of arrhythmias; however, sustained ventricular arrhythmias are quite uncommon. CASE REPORT A 71-year-old man with a history of hypertension developed a sudden onset of shortness of breath, profuse diaphoresis, lightheadedness, and presyncope. Upon emergency medical services' arrival, an initial electrocardiogram revealed wide complex tachycardia with a heart rate of 220 to 230 beats per min...
December 7, 2020: American Journal of Case Reports
Surendra Dasari, Angela Dispenzieri, Shareef Mansour, Prasuna Muppa, Paul J Kurtin, Jason D Theis, Julie A Vrana, Martha Grogan, Taxiarchis Kourelis, Morie A Gertz, Ellen D McPhail
AIMS: Cardiac scintigraphy, a non-invasive technique for diagnosing ATTR cardiac amyloidosis, lacks specificity in patients with concomitant monoclonal gammopathy (up to 40% of cases). For these patients, amyloid type is often established by endomyocardial biopsy (EMB), which has clinical risk. This study aimed to investigate the frequency of ATTR in amyloid-positive tendon/synovium, urinary bladder, and prostate biopsies, sites for which prior biopsy specimens might exist for patients suspected of having cardiac amyloidosis, and, when available, determine the amyloid type concordance rate with other anatomic sites and provide clinical data regarding subsequent development of cardiac amyloidosis...
December 5, 2020: ESC Heart Failure
P Eldhagen, S Berg, L H Lund, P Sörensson, O B Suhr, P Westermark
BACKGROUND: Wild-type transthyretin (ATTRwt) amyloidosis is the most common systemic amyloidosis in western countries and manifests mainly as progressive restrictive cardiomyopathy. OBJECTIVE: To study the prevalence of ATTR deposits in ligament tissue in patients undergoing surgery for lumbar spinal stenosis and to assess whether these deposits are associated with cardiac amyloidosis. MATERIAL AND METHODS: 250 patients, age 50-89 (54 % women), none with known cardiovascular disease were included...
December 4, 2020: Journal of Internal Medicine
Yoshihiro Sobue, Genzou Takemura, Shunji Kawamura, Toshiyuki Yano, Hiromitsu Kanamori, Shin-Ichiro Morimoto, Hitoshi Matsuo
There are few reports on the coexistence of cardiac amyloid light-chain (AL) amyloidosis and light chain deposition disease (LCDD), despite their similar pathophysiologies caused by plasma-cell dyscrasia. Herein, we report the coexistence of these diseases. A 59-year-old man was referred to our hospital because of exertional dyspnea and hypotension. Renal dysfunction of unknown etiology had been present for 4 years and hemodialysis had been introduced. Severe systolic and diastolic cardiac dysfunction was apparent, accompanied with dilatation and granular sparkling, but not with left ventricular hypertrophy...
November 29, 2020: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Azka Latif, Noman Lateef, Faryal Razzaq, Vikas Kapoor, Muhammad Junaid Ahsan, Muhammad Ashfaq, Ahmad Iftikhar, Faiz Anwer, Mark Holmberg, Preethi William
The estimated prevalence of AL CA in the US is approximately 8-12 cases per million. Almost 30-50% diagnosed cases of AL amyloid in the US have multisystem involvement including cardiac involvement. Even with the availability of advanced diagnostic testing and novel therapies, prognosis remains poor. It is overlooked as a cause of heart failure with preserved ejection fraction leading to a delay in diagnosis when management options are limited and associated with poor survival outcomes. Therefore, the education of physicians is needed to ensure that it would be highly considered as a differential diagnosis...
November 29, 2020: Cardiovascular & Hematological Disorders Drug Targets
Stanley Walls, Soda Diop, Ryan Birse, Lisa Elmen, Zhuohui Gan, Sreehari Kalvakuri, Santiago Pineda, Curran Reddy, Erika Taylor, Bosco Trinh, Georg Vogler, Rachel Zarndt, Andrew McCulloch, Peter Lee, Sharmila Bhattacharya, Rolf Bodmer, Karen Ocorr
Understanding the effects of microgravity on human organs is crucial to exploration of low-earth orbit, the moon, and beyond. Drosophila can be sent to space in large numbers to examine the effects of microgravity on heart structure and function, which is fundamentally conserved from flies to humans. Flies reared in microgravity exhibit cardiac constriction with myofibrillar remodeling and diminished output. RNA sequencing (RNA-seq) in isolated hearts revealed reduced expression of sarcomeric/extracellular matrix (ECM) genes and dramatically increased proteasomal gene expression, consistent with the observed compromised, smaller hearts and suggesting abnormal proteostasis...
November 23, 2020: Cell Reports
Andrew Js Coats
The Metabolic Exercise combined with Cardiac and Kidney Indexes [MECKI) score is a validated prognostic score for heart failure with reduced ejection fraction which combines commonly available clinical and metabolic parameters with two cardiopulmonary exercise test derived prognostic measurements. It has been validated to predict prognosis and to aid clinical decision making and it has been shown to be superior in predicting mortality compared with other commonly used prognostic scores for heart failure. In the future it would be valuable to establish whether the score holds true also in other settings, and in particular in under-represented groups - the elderly, women, and people of different ethnic backgrounds - and in other heart failure syndromes...
December 2020: European Journal of Preventive Cardiology
Emad U Alatassi, Alaa Mohamed, Salim Habib, Iyiad Alabdul Razzak, Anas Mahmoud
Amyloidosis is a rare multisystem disease due to deposition of abnormal protein fragments, and cardiac amyloidosis is progressive and difficult to diagnose due to its subtle and non-specific symptoms unless the physician maintains a high degree of suspicion. This case report focuses on amyloid deposition in the heart of an 84-year-old woman who presented with symptoms of uncompensated heart failure.
October 19, 2020: Curēus
Lisa Dannenberg, Kajetan Trojovsky, Aysel Ayhan, Carolin Helten, Saif Zako, René M'Pembele, Philipp Mourikis, Marcel Benkhoff, Denis Ignatov, Theresia Sarabhai, Tobias Petzold, Ragnar Huhn-Wientgen, Tobias Zeus, Malte Kelm, Bodo Levkau, Amin Polzin
BACKGROUND: Targeting inflammation in patients with coronary artery disease and/or acute myocardial infarction (AMI) is a matter of debate. Methotrexate (MTX) is one of the most widely used immunosuppressants. Cardiovascular Inflammation Reduction Trial (CIRT) recently failed to demonstrate reduced cardiovascular events in MTX-treated patients. However, it is not known if long-term MTX treatment improves cardiac outcome in AMI. Therefore, in this study, we investigated the postischemic phase in MTX-treated mice undergoing AMI...
November 20, 2020: Pharmacology
Timothy J Poterucha, Pierre Elias, Sabahat Bokhari, Andrew J Einstein, Albert DeLuca, Mona Kinkhabwala, Lynne L Johnson, Kathleen R Flaherty, Sunil E Saith, Jan M Griffin, Adler Perotte, Mathew S Maurer
OBJECTIVES: This study aimed to characterize trends in technetium Tc 99m pyrophosphate (99m Tc-PYP) scanning for amyloid transthyretin cardiac amyloidosis (ATTR-CA) diagnosis, to determine whether patients underwent appropriate assessment with monoclonal protein and genetic testing, to evaluate use of single-photon emission computed tomography (SPECT) in addition to planar imaging, and to identify predictive factors for ATTR-CA. BACKGROUND: 99m Tc-PYP scintigraphy has been repurposed for noninvasive diagnosis of ATTR-CA...
November 12, 2020: JACC. Cardiovascular Imaging
C Rischpler, T Schlosser, L Umutlu, T Rassaf, B J Krause
CLINICAL/METHODOLOGICAL ISSUE: The goal of this article is to shed light on innovations in perfusion imaging and the fields of application that have opened up in hybrid imaging of the heart. STANDARD RADIOLOGICAL METHODS: As before, the most commonly used modalities in hybrid imaging are single photon emission computed tomography (SPECT) and positron emission tomography/computed tomography (PET/CT). Perfusion tracers and the radioactively labeled glucose analog 18 F‑fluorodeoxyglucose (FDG) are commonly used for vitality imaging...
December 2020: Der Radiologe
Kathleen W Zhang, Ray Zhang, Elena Deych, Keith E Stockerl-Goldstein, John Gorcsan, Daniel J Lenihan
BACKGROUND: Timely recognition of cardiac amyloidosis is clinically important, but the diagnosis is frequently delayed. OBJECTIVES: We sought to identify a multi-modality approach with the highest diagnostic accuracy in patients evaluated by cardiac biopsy, the diagnostic gold standard. METHODS: Consecutive patients (N = 242) who underwent cardiac biopsy for suspected amyloidosis within an 18-year period were retrospectively identified...
November 17, 2020: American Heart Journal
Krister Lindmark, Björn Pilebro, Torbjörn Sundström, Per Lindqvist
AIMS: Wild type transthyretin amyloidosis (ATTRwt) has gained interest during recent years due to better diagnostic tools and the emergence of treatment options. Little is known about the prevalence of the disease. We aimed to investigate the prevalence in a heart failure population with myocardial hypertrophy. METHODS AND RESULTS: All patients with an ICD code of heart failure living within the catchment area of Umeå University hospital and intraventricular septum >14 mm were offered screening with 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scan and a clinical work up...
November 17, 2020: ESC Heart Failure
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