Pubblicazioni recenti - cardiac amyloidosis
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Arrhythmic Risk Stratification in Cardiac Amyloidosis: A Review of the Current Literature.
J Cardiovasc Dev Dis2024 Jul;11(7):. doi: 222.
Bonvicini Eleonora, Preda Alberto, Tognola Chiara, Falco Raffaele, Gidiucci Roberto, Leo Giulio, Vargiu Sara, Varrenti Marisa, Gigli Lorenzo, Baroni Matteo, Carbonaro Marco, Colombo Giulia, Maloberti Alessandro, Giannattasio Cristina, Mazzone Patrizio, Guarracini Fabrizio,
Abstract
Cardiac amyloidosis is the most frequent infiltrative disease caused by the deposition of misfolded proteins in the cardiac tissue, leading to heart failure, brady- and tachyarrhythmia and death. Conduction disorders, atrial fibrillation (AF) and ventricular arrhythmia (VA) significantly impact patient outcomes and demand recognition. However, several issues remain unresolved regarding early diagnosis and optimal management. Extreme bradycardia is the most common cause of arrhythmic death, while fast and sustained VAs can be found even in the early phases of the disease. Risk stratification and the prevention of sudden cardiac death are therefore to be considered in these patients, although the time for defibrillator implantation is still a subject of debate. Moreover, atrial impairment due to amyloid fibrils is associated with an increased risk of AF resistant to antiarrhythmic therapy, as well as recurrent thromboembolic events despite adequate anticoagulation. In the last few years, the aging of the population and progressive improvements in imaging methods have led to increases in the diagnosis of cardiac amyloidosis. Novel therapies have been developed to improve patients' functional status, quality of life and mortality, without data regarding their effect on arrhythmia prevention. In this review, we consider the latest evidence regarding the arrhythmic risk stratification of cardiac amyloidosis, as well as the available therapeutic strategies.
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Prognostic Value of Serum Galectin-3 for Survival in Patients with Cardiac Light-Chain Amyloidosis.
J Cardiovasc Dev Dis2024 Jun;11(7):. doi: 202.
Yang Xinglin, Huang Jin, Zhang Jinghong, Li Jian, Tian Zhuang,
Abstract
BACKGROUND:
Amyloid light-chain (AL) amyloidosis is a multisystem disorder, with cardiac amyloid infiltration being a prevalent manifestation. This study aimed to explore the prognostic value of galectin-3 (Gal-3), a soluble marker associated with fibrosis, inflammation, heart failure, and kidney injury, in patients with cardiac AL amyloidosis.
METHODS:
A total of 60 patients who were diagnosed with cardiac AL amyloidosis from January 2015 to May 2018 were enrolled. The prognostic value of Gal-3 was assessed. Receiver operating characteristic (ROC) curves were used to evaluate the predictive accuracy of Gal-3. A Gal-3 cut-off value was identified to predict survival rates.
RESULTS:
The ROC curves demonstrated a moderate predictive accuracy of Gal-3 for 0.5- and 5-year survival, with area under the curve (AUC) values of 0.722 and 0.788, respectively. A Gal-3 cut-off value of 15.154 ng/mL was found to predict survival. Kaplan-Meier survival analysis revealed a significant difference in mean overall survival between patients with Gal-3 levels below and above the established cut-off (69.2 months versus 42.1 months, respectively; = 0.036). Multivariate analysis confirmed that Gal-3 > 15.154 ng/mL remained an independent predictor of survival (HR 2.451, 95% CI 1.017-5.910, = 0.046).
CONCLUSIONS:
This study suggests that Gal-3 holds independent prognostic value for survival in patients with cardiac AL amyloidosis. Gal-3 could potentially enhance the prognostic capabilities of the current soluble markers, thereby improving the management of cardiac AL amyloidosis. However, further validation in larger prospective studies is warranted.
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Molecular basis for non-invasive diagnostics of cardiac amyloids using bone tracers.
Biomater Sci2024 Jul;():. doi: 10.1039/d4bm00816b.
Lewkowicz Emily, Jayaraman Shobini, Gursky Olga,
Abstract
Amyloid diseases including Alzheimer's, Parkinson's and over 30 others are incurable life-threatening disorders caused by abnormal protein deposition as fibrils in various organs. Cardiac amyloidosis is particularly challenging to diagnose and treat. Identification of the fibril-forming protein, which in the heart is usually amyloid transthyretin (ATTR) or amyloid immunoglobulin light chain (AL), is paramount to treatment. A transformative non-invasive diagnostic modality is imaging using technetium-labeled pyrophosphate or diphosphonate bone tracers, Tc-PYP/DPD/HMDP. For unknown reasons, these tracers show preferential uptake by ATTR deposits. The tracer-binding moiety is unknown and potentially involves amyloid fibrils and/or amyloid-associated calcific deposits. We propose that, like in the bone, the tracers chelate to surface-bound Ca in amyloid. In high-affinity protein sites, Ca is coordinated by pairs of acidic residues. To identify such residues on amyloids, we harnessed atomic structures of patient-derived cardiac amyloids determined using cryogenic electron microscopy since 2019. These structures help explain why most but not all ATTR deposits uptake Tc-PYP/DPD/HMDP radiotracers, while in AL the opposite is true. Moreover, fibril structures help explain greater microcalcification observed in ATTR AL deposits. These findings may aid the diagnostics and therapeutic targeting of cardiac amyloidosis and are relevant to other amyloids.
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Severe Heart Failure after Using Bortezomib in a Patient with Multiple Myeloma and Cardiac Amyloidosis of Normal Wall Thickness.
Acta Cardiol Sin2024 Jul;40(4):454-457. doi: 10.6515/ACS.202407_40(4).20240410A.
Kao Ting-Wei, Huang Tai-Chung, Liao Che-Wei, Shun Chia-Tung, Tsai Cheng-Hsuan, Lin Yen-Hung,
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Appraisal of amyloidosis imaging practices in the Middle East/North Africa (PYP-MENA).
Eur Heart J Imaging Methods Pract2024 Jan;2(1):qyad025. doi: qyad025.
Al Badarin Firas, Garashi Masoud, Aljizeeri Ahmed, Tabbalat Ramzi, Allam Adel, Bouyoucef Salah Eddine, Chauhdary Ammar,
Abstract
AIMS:
Whereas recommendations to optimize performance and yield of cardiac scintigraphy studies with bone-seeking tracers have been published, little is known about real-world adherence to these best practices, especially outside North America and Europe. Accordingly, we described imaging practices with this modality in a sample of nuclear laboratories in the Middle East/North Africa (MENA) region.
METHODS AND RESULTS:
Laboratories performing radionuclide imaging for cardiac amyloidosis in the MENA region were invited to participate in this study to describe installed camera systems, type and dose of bone-avid tracers used, imaging protocols, and criteria used for study interpretation. Out of 19 invited sites, 10 completed the survey (70% government-run; 90% accredited), sites have been involved with amyloid imaging for a median of 49 months (interquartile range 24-60). The median injected dose was 20?mCi (range 10-25), and PYP was used by 90% of sites in this sample. Planar imaging with single photon emission computed tomography (SPECT) reconstruction was performed at all sites, including seven sites that performed SPECT/CT reconstruction. Lastly, only 50% of sites relied on evidence of myocardial uptake by SPECT to confirm the diagnosis of ATTR cardiomyopathy, while the rest relied on visual assessment and heart/contralateral ratio.
CONCLUSION:
This study is the first to describe variation in imaging practices across sites in the MENA region, especially in acquisition protocols and interpretation standards. Eliminating heterogeneities identified by this study will harmonize image interpretation and reporting and will facilitate successful conduct of regional multi-centre studies.
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.
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Quantification of myocardial extracellular volume without blood sampling.
Eur Heart J Imaging Methods Pract2023 Sep;1(2):qyad022. doi: qyad022.
Chen Wensu, Faragli Alessandro, Goetze Collin, Zieschang Victoria, Weiss Karl Jakob, Hashemi Djawid, Beyer Rebecca, Hafermann Lorena, Stawowy Philipp, Kelle Sebastian, Doeblin Patrick,
Abstract
AIMS:
Cardiac magnetic resonance (CMR) 1 relaxation time mapping is an established technique primarily used to identify diffuse interstitial fibrosis and oedema. The myocardial extracellular volume (ECV) can be calculated from pre- and post-contrast 1 relaxation times and is a reproducible parametric index of the proportion of volume occupied by non-cardiomyocyte components in myocardial tissue. The conventional calculation of the ECV requires blood sampling to measure the haematocrit (HCT). Given the high variability of the HCT, the blood collection is recommended within 24?h of the CMR scan, limiting its applicability and posing a barrier to the clinical routine use of ECV measurements. In recent years, several research groups have proposed a method to determine the ECV by CMR without blood sampling. This is based on the inverse relationship between the 1 relaxation rate (1) of blood and the HCT. Consequently, a 'synthetic' HCT could be estimated from the native blood 1, avoiding blood sampling.
METHODS AND RESULTS:
We performed a review and meta-analysis of published studies on synthetic ECV, as well as a secondary analysis of previously published data to examine the effect of the chosen regression modell on bias. While, overall, a good correlation and little bias between synthetic and conventional ECV were found in these studies, questions regarding its accuracy remain.
CONCLUSION:
Synthetic HCT and ECV can provide a 'non-invasive' quantitative measurement of the myocardium's extracellular space when timely HCT measurements are not available and large alterations in ECV are expected, such as in cardiac amyloidosis. Due to the dependency of 1 relaxation times on the local setup, calculation of local formulas using linear regression is recommended, which can be easily performed using available data.
© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
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RNA Interference Therapeutics for Hereditary Amyloidosis: A Narrative Review of Clinical Trial Outcomes and Future Directions.
Cureus2024 Jun;16(6):e62981. doi: e62981.
Dave Prashil, Anand Puneet, Kothawala Azra, Srikaram Prakhyath, Shastri Dipsa, Uddin Anwar, Bhavsar Jill, Winer Andrew,
Abstract
Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant, life-threatening genetic disorder caused by a single-nucleotide variant in the transthyretin gene. This mutation leads to the misfolding and deposition of amyloid in various body organs. Both mutant and wild-type transthyretin contribute to the resulting polyneuropathy and cardiomyopathy, leading to significant sensorimotor disturbances and severe cardiac conditions such as heart failure and arrhythmias, thereby impacting quality of life. Despite several treatments, including orthotopic liver transplantation and transthyretin tetramer stabilizers, their limitations persisted until the introduction of RNA interference (RNAi). RNAi, a means to regulate mRNA stability and translation of targeted genes, has brought about significant changes in treatment strategies for ATTR with the introduction of patisiran in 2018. This study reviews patisiran, vutrisiran, inotersen, and eplontersen, developed for the treatment of ATTR. It provides an overview of the clinical trial outcomes, focusing mainly on quality of life, adverse reactions, and the future of RNAi-based therapies.
Copyright © 2024, Dave et al.
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Altered connectivity of central autonomic network: effects of dysautonomia in hereditary transthyretin amyloidosis with polyneuropathy.
Amyloid2024 Jul;():1-9. doi: 10.1080/13506129.2024.2383450.
Su Tsai-Jou, Lin Chien-Ho Janice, Liu Yen-Lin, Hsueh Hsueh-Wen, Hsieh Sung-Tsang, Chao Chi-Chao, Chiang Ming-Chang,
Abstract
BACKGROUND:
Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a progressive fatal disorder caused by deposition of mutant transthyretin (TTR) amyloids mainly in the nerves and heart. Autonomic dysfunction is a major disabling manifestation, affecting 90% of patients with late-onset ATTRv-PN. The current study aimed to investigate brain functional alterations associated with dysautonomia due to peripheral autonomic nerve degeneration in ATTRv-PN.
METHODS:
Resting-state functional MRI data were acquired from 43 ATTRv-PN patients predominantly of A97S (p.A117S) genotype, and the functional connectivity of central autonomic regions was assessed.
RESULTS:
Compared with age-matched healthy controls, the ATTRv-PN patients exhibited (1) reduced functional connectivity of the central autonomic regions such as hypothalamus, amygdala, anterior insula, and middle cingulate cortex with brain areas of the limbic, frontal, and somatosensory systems, and (2) correlations of reduced functional autonomic connectivity with the severity of autonomic dysfunction especially orthostatic intolerance, decreased heart rate variability, and greater clinical disability.
CONCLUSIONS:
Our findings provide evidence linking peripheral autonomic dysfunction with altered connectivity in the central autonomic network in ATTRv-PN.
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Determinants of transthyretin levels and their association with adverse clinical outcomes among UK Biobank participants.
Nat Commun2024 Jul;15(1):6221. doi: 6221.
Shetty Naman S, Gaonkar Mokshad, Patel Nirav, Pampana Akhil, Vekariya Nehal, Li Peng, Arora Garima, Arora Pankaj,
Abstract
Transthyretin is a transport protein whose misfolding has been implicated in the development of cardiac amyloidosis. Here, we examine the clinical correlates of transthyretin levels, the differences in transthyretin levels according to the pathogenic V142I TTR variant carrier status, and the association of transthyretin levels with outcomes among 35,206 UK Biobank participants who underwent plasma profiling and were free from prevalent cardiovascular disease and chronic renal disease. Transthyretin levels are lower in females, decrease with increasing C-reactive protein levels, and increase with body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, albumin levels, triglyceride levels, and creatinine levels. V142I non-carriers [n?=?35,167, mean: -0.1 (0.3)] have higher adjusted transthyretin levels compared with the carriers [n?=?39, mean: -0.5 (0.3)] (p:
© 2024. The Author(s).
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A commentary on 'Meta-analysis of post-transcatheter aortic valve replacement outcomes in patients with cardiac amyloidosis and aortic stenosis'.
Int J Surg2024 Jul;110(7):4418-4419. doi: 10.1097/JS9.0000000000001271.
Ji Mingyue, Pu Juan, Jiang Lili, Wang Xinwei, Zuo Caojian,
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Effect of beta-blockade on mortality in patients with cardiac amyloidosis: A systematic review and meta-analysis.
ESC Heart Fail2024 Jul;():. doi: 10.1002/ehf2.14975.
Kwok Chun Shing, Choy Chern Hsiang, Pinney Jennifer, Townend Jonathan N, Whelan Carol, Fontana Marianna, Gillmore Julian D, Steeds Richard P, Moody William E,
Abstract
AIMS:
The efficacy of beta-blockers in cardiac amyloidosis (CA) is unclear, and concerns persist that neurohormonal blockade could worsen symptoms of heart failure. We aimed to assess whether beta-blocker therapy is associated with improved survival in patients with CA.
METHODS AND RESULTS:
We conducted a systematic review and meta-analysis to examine the impact of beta-blocker therapy on mortality in patients with CA. A search of MEDLINE and EMBASE was performed in August 2023. Data were extracted from observational studies and synthesized with pooling and random effects meta-analysis. Thirteen studies including 4215 patients with CA were incorporated in this review (3688 transthyretin amyloid cardiomyopathy (ATTR-CM), 502 light chain amyloid cardiomyopathy (AL-CM), 25 not specified; age 74.8 ± 5.5 years, 76% male). Over half of the cohort (52%) received beta-blockers and the rate of beta-blocker withdrawal was 28%. All-cause mortality was 33% (range: 13-51%) after a median follow-up ranging from 13 to 36 months. There was an inverse association between the pooled risk of mortality and the use of beta-blocker therapy at any time point (RR 0.48, 95% CI 0.29-0.80, I = 83%, P = 0.005, seven studies). There was no association between mortality and beta-blocker use (RR 0.65, 95% CI 0.29-1.47, I = 88%, P = 0.30) in the three studies that only included patients with ATTR-CM. The three studies that included patients with both ATTR-CM and AL demonstrated an association of beta-blocker use with reduced mortality (OR 0.43, 95% CI 0.29-0.63, I = 4%, P
CONCLUSIONS:
Treatment with beta-blockers may be associated with a survival benefit in patients with CA, but these findings are subject to selection and survivor biases. Definitive prospective randomized trials of conventional heart failure therapies are needed in CA.
© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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The value of myocardial contraction fraction and long-axis strain to predict late gadolinium enhancement in multiple myeloma patients with secondary cardiac amyloidosis.
Sci Rep2024 Jul;14(1):16832. doi: 16832.
Hu Mengyao, Song Yipei, Yang Chunhua, Wang Jiazhao, Zhu Wei, Kan Ao, Yang Pei, Dai Jiankun, Yu Honghui, Gong Lianggeng,
Abstract
The aim of this study is to assess the effectiveness of conventional and two additional functional markers derived from standard cardiac magnetic resonance (CMR) images in detecting the occurrence of late gadolinium enhancement (LGE) in patients with secondary cardiac amyloidosis (CA) related to multiple myeloma (MM). This study retrospectively included 32 patients with preserved ejection fraction (EF) who had MM-CA diagnosed consecutively. Conventional left ventricular (LV) function markers and two additional functional markers, namely myocardial contraction fraction (MCF) and LV long-axis strain (LAS), were obtained using commercial cardiac post-processing software. Logistic regression analyses and receiver operating characteristic (ROC) analysis were performed to evaluate the predictive performances. (1) There were no notable distinctions in clinical features between the LGE+?and LGE- groups, with the exception of a reduced systolic blood pressure in the former (105.60?±?18.85 mmHg vs. 124.50?±?20.95 mmHg, P?=?0.022). (2) Patients with MM-CA presented with intractable heart failure with preserved ejection fraction (HFpEF). The LVEF in the LGE+?group exhibited a greater reduction (54.27%, IQR 51.59-58.39%) in comparison to the LGE- group (P?0.05). And MM-CA patients with LGE+?had significantly higher LVMI (90.15?±?23.69 g/m), lower MCF (47.39%, IQR 34.28-54.90%), and the LV LAS were more severely damaged (- 9.94?±?3.42%) than patients with LGE- (all P values?0.05). (3) The study found that MCF exhibited a significant independent association with LGE, as indicated by an odds ratio of 0.89 (P?0.05). The cut-off value for MCF was determined to be 64.25% with a 95% confidence interval ranging from 0.758 to 0.983. The sensitivity and specificity of this association were calculated to be 95% and 83%, respectively. MCF is a simple reproducible predict marker of LGE in MM-CA patients. It is a potentially CMR-based method that promise to reduce scan times and costs, and boost the accessibility of CMR.
© 2024. The Author(s).
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Transthyretin amyloidosis in spinal canal stenosis: A systematic review.
J Orthop2024 Jul;53():133-139. doi: 10.1016/j.jor.2024.02.047.
Moore Zachary J, Rizkalla James M, Weiner Joseph, Lawrence Brandon, Spina Nicolas, Spiker Ryan, Brodke Darrel, Karamian Brian,
Abstract
We systematically review literature regarding the contribution of transthyretin amyloidosis to spinal stenosis. Amyloidosis is a protein misfolding condition that causes systemic deposition of amyloid and commonly leads to heart failure and nephropathy. A growing body of literature suggests that amyloid deposits within the ligamentum flavum are frequently associated with spinal stenosis with subsequent myelopathy. Our search identified 67 publications from the PubMed database for literature review. After evaluating the inclusion and exclusion criteria, a total of 18 articles were included in the review. Each article was evaluated for country, study type, sample size, amyloidosis subtype, spinal level, systemic symptoms, treatment, patient outcome, and conclusions. Many studies concluded that lumbar ligamentum flavum hypertrophy is more severe in patients with amyloidosis due to associated amyloid deposition. Additionally, patients with systemic amyloidosis are more likely to have recurrence of spinal stenosis. Multiple studies encourage routine screening be performed on spinal stenosis patients to target those needing cardiac surveillance. Amyloid deposition is frequently associated with spinal stenosis, and its presence may provide an earlier opportunity to diagnose or predict systemic amyloidosis. Surgeons should consider obtaining intraoperative biopsy to identify amyloidosis and inform screening postoperatively. Finally, physicians should be aware of this association and counsel patients accordingly on the risks and treatment options available for amyloidosis.
© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.
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Transthyretin Cardiac Amyloidosis in an Elderly Male With Heart Failure Intolerant to Guideline-Directed Medical Therapy.
Cureus2024 Jun;16(6):e62722. doi: e62722.
Ene Noah, Ingram Toyin, Bhandari Manoj,
Abstract
Cardiac amyloidosis arises when there is a deposition of abnormal proteins, called amyloids, in the myocardium. It can manifest as overt heart failure, conduction abnormalities, atrial and ventricular arrhythmia, cardiomyopathy, and aortic stenosis. Two main types of proteins identified in cardiac amyloidosis are light-chain amyloid and transthyretin amyloid. Cardiac amyloidosis, although common, is an underdiagnosed cause of heart failure in many cases. A high index of suspicion is needed to make a diagnosis, given that symptoms are not specific. Early diagnosis and treatment of cardiac amyloidosis are associated with reduced morbidity and improved survival. We present a case of a 73-year-old African American male with decompensated heart failure with reduced ejection fraction intolerant to guideline-directed medical therapy who was later found to have cardiac amyloidosis.
Copyright © 2024, Ene et al.
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The Impact of Iron Deficiency on Disease Severity and Myocardial Function in Cardiac Amyloidosis.
Am J Med Open2024 Jun;11():100063. doi: 100063.
Martens Pieter, Ives Lauren, Nguyen Christopher, Kwon Deborah, Hanna Mazen, Tang W H Wilson,
Abstract
BACKGROUND:
Reduced cardiac energy is a hallmark feature of heart failure and is common in cardiac amyloidosis (CA) and can be aggravated by the presence of iron deficiency.
METHODS:
Retrospective analysis of a single tertiary care center CA registry. Prevalence of iron deficiency was determined based on two definitions: (1) Classic definition, ferritin
RESULTS:
Out of a total of 393 CA patients who had a full set of iron indices (44% light chain [AL]-CA, 50% transthyretin [ATTR]-CA, remainder other or unspecified CA subtype), 56% had iron deficiency according to the classic definition and 58% according to the TSAT definition, with similar prevalence in AL-CA vs ATTR-CA ( = .135). Per both definitions 58% had anemia. Only the TSAT-based definition was associated with worse functional status ( = .039) and worse cardiac function. CA patients with a TSAT
CONCLUSION:
Iron deficiency is common in cardiac amyloidosis and, when identified with a TSAT
© 2023 The Author(s).
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Systemic aging fuels heart failure: Molecular mechanisms and therapeutic avenues.
ESC Heart Fail2024 Jul;():. doi: 10.1002/ehf2.14947.
Fang Zhuyubing, Raza Umar, Song Jia, Lu Junyan, Yao Shun, Liu Xiaohong, Zhang Wei, Li Shujuan,
Abstract
Systemic aging influences various physiological processes and contributes to structural and functional decline in cardiac tissue. These alterations include an increased incidence of left ventricular hypertrophy, a decline in left ventricular diastolic function, left atrial dilation, atrial fibrillation, myocardial fibrosis and cardiac amyloidosis, elevating susceptibility to chronic heart failure (HF) in the elderly. Age-related cardiac dysfunction stems from prolonged exposure to genomic, epigenetic, oxidative, autophagic, inflammatory and regenerative stresses, along with the accumulation of senescent cells. Concurrently, age-related structural and functional changes in the vascular system, attributed to endothelial dysfunction, arterial stiffness, impaired angiogenesis, oxidative stress and inflammation, impose additional strain on the heart. Dysregulated mechanosignalling and impaired nitric oxide signalling play critical roles in the age-related vascular dysfunction associated with HF. Metabolic aging drives intricate shifts in glucose and lipid metabolism, leading to insulin resistance, mitochondrial dysfunction and lipid accumulation within cardiomyocytes. These alterations contribute to cardiac hypertrophy, fibrosis and impaired contractility, ultimately propelling HF. Systemic low-grade chronic inflammation, in conjunction with the senescence-associated secretory phenotype, aggravates cardiac dysfunction with age by promoting immune cell infiltration into the myocardium, fostering HF. This is further exacerbated by age-related comorbidities like coronary artery disease (CAD), atherosclerosis, hypertension, obesity, diabetes and chronic kidney disease (CKD). CAD and atherosclerosis induce myocardial ischaemia and adverse remodelling, while hypertension contributes to cardiac hypertrophy and fibrosis. Obesity-associated insulin resistance, inflammation and dyslipidaemia create a profibrotic cardiac environment, whereas diabetes-related metabolic disturbances further impair cardiac function. CKD-related fluid overload, electrolyte imbalances and uraemic toxins exacerbate HF through systemic inflammation and neurohormonal renin-angiotensin-aldosterone system (RAAS) activation. Recognizing aging as a modifiable process has opened avenues to target systemic aging in HF through both lifestyle interventions and therapeutics. Exercise, known for its antioxidant effects, can partly reverse pathological cardiac remodelling in the elderly by countering processes linked to age-related chronic HF, such as mitochondrial dysfunction, inflammation, senescence and declining cardiomyocyte regeneration. Dietary interventions such as plant-based and ketogenic diets, caloric restriction and macronutrient supplementation are instrumental in maintaining energy balance, reducing adiposity and addressing micronutrient and macronutrient imbalances associated with age-related HF. Therapeutic advancements targeting systemic aging in HF are underway. Key approaches include senomorphics and senolytics to limit senescence, antioxidants targeting mitochondrial stress, anti-inflammatory drugs like interleukin (IL)-1? inhibitors, metabolic rejuvenators such as nicotinamide riboside, resveratrol and sirtuin (SIRT) activators and autophagy enhancers like metformin and sodium-glucose cotransporter 2 (SGLT2) inhibitors, all of which offer potential for preserving cardiac function and alleviating the age-related HF burden.
© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Clinical and genetic profiles of patients with hereditary and wild-type transthyretin amyloidosis: the Transthyretin Cardiac Amyloidosis Registry in the state of São Paulo, Brazil (REACT-SP).
Orphanet J Rare Dis2024 Jul;19(1):273. doi: 273.
Fernandes Fábio, Luzuriaga Georgina Del Cisne Jadán, da Fonseca Guilherme Wesley Peixoto, Correia Edileide Barros, Carvalho Alzira Alves Siqueira, Macedo Ariane Vieira Scarlatelli, Coelho-Filho Otavio Rizzi, Scheinberg Phillip, Antunes Murillo Oliveira, Schwartzmann Pedro Vellosa, Mangini Sandrigo, Marques Wilson, Simões Marcus Vinicius,
Abstract
BACKGROUND:
Transthyretin amyloidosis (ATTR) is a multisystem disease caused by the deposition of fibrillar protein in organs and tissues. ATTR genotypes and phenotypes are highly heterogeneous. We present data on physical signs and symptoms, cardiac and neurological assessments and genetic profile of patients enrolled in the Transthyretin Cardiac Amyloidosis Registry of the State of São Paulo, Brazil.
RESULTS:
Six hundred-forty-four patients were enrolled, 505 with the variant form (ATTRv) and 139 with wild-type (ATTRwt). Eleven different mutations were detected, the most common being Val50Met (47.5%) and V142Ile (39.2%). Overall, more than half of the patients presented cardiac involvement, and the difference in this proportion between the ATTRv and ATTRwt groups was significant (43.9 vs. 89.9%; p?0.001). The prevalence of the neurological phenotype also differed between ATTRv and ATTRwt (56.8 vs. 31.7%; p?0.001). The mixed phenotype was found in 25.6% of the population, without a significant difference between ATTRv and ATTRwt groups. A group of patients remained asymptomatic (10.4%), with a lower proportion of asymptomatic ATTRwt patients.
CONCLUSIONS:
This study details the clinical and genetic spectrum of patients with ATTR in São Paulo, Brazil. This preliminary analysis highlights the considerable phenotypic heterogeneity of neurological and cardiac manifestations in patients with variant and wild-type ATTR.
© 2024. The Author(s).
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Cardiac amyloidosis worsens prognosis in patients with heart failure: Findings from the PREVAMIC study.
Rev Clin Esp (Barc)2024 Jul;():. doi: S2254-8874(24)00100-0.
Ruiz Hueso R, Salamanca Bautista P, Quesada Simón M A, Yun S, Conde Martel A, Morales Rull J L, Fiteni Mera I, Abad Pérez D, Páez Rubio I, Aramburu Bodas Ó, ,
Abstract
BACKGROUND AND OBJECTIVES:
Cardiac amyloidosis (CA) is a common pathology in elderly patients that usually presents as heart failure (HF). However, it is not clear whether CA associated with HF has a worse prognosis compared with HF due to other etiologies.
MATERIAL AND METHODS:
Prospective, observational cohort study that recruited patients ?65 years of age with HF in 30 Spanish centers. The cohort was divided according to whether the patients had AC or not. Patients were followed for 1?year.
RESULTS:
A total of 484 patients were included in the analysis. The population was elderly (median 86 years) and 49% were women CA was present in 23.8 % of the included patients. In the CA group, there was a lower prevalence of diabetes mellitus and valvular disease. At one year of follow-up, mortality was significantly more frequent in patients with CA compared to those without (33.0 vs.14.9%, p?0.001). However, there were no differences between both groups in visits to the emergency room or readmissions. In the multivariate analysis, the variables that were shown to predict all-cause mortality at one year of follow-up were chronic kidney disease (HR 1.75 (1.01-3.05) p?0.045), NT-proBNP levels (HR 2.51 (1.46-4.30) p?0.001), confusion (HR 2.05 (1.01-4.17), p?0.048), and the presence of CA (HR 1.77 (1.11-2.84), p?0.017).
CONCLUSION:
The presence of CA in elderly patients with HF is related to a worse prognosis at one year of follow-up. Early diagnosis of the pathology and multidisciplinary management can help improve patient outcomes.
Copyright © 2024 Sociedad Española de Medicina Interna (SEMI). Published by Elsevier España, S.L.U. All rights reserved.
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Antithrombotic properties of Tafamidis: An additional protective effect for transthyretin amyloid cardiomyopathy patients.
Vascul Pharmacol2024 Jul;156():107411. doi: 10.1016/j.vph.2024.107411.
Ministrini Stefano, Niederberger Rebecca, Akhmedov Alexander, Beer Georgia, Puspitasari Yustina M, Franzini Maria, Vergaro Giuseppe, Cannie Douglas E, Elliott Perry, Kahr Peter C, Hock Christoph, Kobza Richard, Toggweiler Stefan, Lüscher Thomas F, Camici Giovanni G, Stämpfli Simon F,
Abstract
INTRODUCTION:
Tafamidis is a molecular chaperone that stabilizes the transthyretin (TTR) homo-tetramer, preventing its dissociation and consequent deposition as amyloid fibrils in organ tissues. Tafamidis reduces mortality and the incidence of hospitalization for cardiovascular causes in patients with TTR amyloid (ATTR) cardiomyopathy. As ATTR cardiomyopathy is associated with a high risk of thromboembolic complications, we hypothesized that tafamidis may have a direct ancillary anti-thrombotic effect.
METHODS:
Primary human aortic endothelial cells (HAECs) were treated with tafamidis at clinically relevant concentrations and with plasma of patients, before and after the initiation of treatment with tafamidis. The expression of TF was induced by incubation with Tumor Necrosis Factor ? (TNF?). Intracellular expression of tissue factor (TF) was measured by western blot. TF activity was measured by a colorimetric assay. Gene expressions of TF were measured by quantitative polymerase chain reaction.
RESULTS:
Treatment with tafamidis dose-dependently reduced the expression and activity of TNF?-induced TF. This effect was confirmed in cells treated with patients' plasma. Signal Transducer and Activator of Transcription 3 (STAT3) phosphorylation was significantly inhibited by tafamidis. Incubation of HAECs with tafamidis and the STAT3 activator colivelin partially rescued the expression of TF.
CONCLUSIONS:
Treatment with tafamidis lowers the thrombotic potential in human primary endothelial cells by reducing TF expression and activity. This previously unknown off-target effect may provide a novel mechanistic explanation for the lower number of thromboembolic complications in ATTR cardiomyopathy patients treated with tafamidis.
Copyright © 2024 Elsevier Inc. All rights reserved.
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Utilizing Alcohol Septal Ablation for Mitigating Left Ventricular Outflow Tract Obstruction in Cardiac Amyloidosis: A Case Report.
Cureus2024 Jun;16(6):e62633. doi: e62633.
Girgis Kyrillos, Feinberg Ari, Retcho Danielle, Elias Tony, George Allen, Gonzalez Garcia Grettel, Beshai Rafail, Chennu Gouthami, Patel Reenal, Cohen Marc,
Abstract
Alcohol septal ablation (ASA) has been widely used in relieving the left ventricular outflow tract (LVOT) obstruction caused by hypertrophic obstructive cardiomyopathy (HOCM). There is limited data about the utility of ASA in cases of cardiac amyloidosis with LVOT obstruction. Our patient is 71-year-old male with a history of multiple myeloma complicated by cardiac amyloidosis and end-stage renal disease on hemodialysis who presented from the dialysis center due to hypotension. The patient was admitted to our hospital for further workup. He underwent echocardiography that showed severely elevated LVOT gradient pressures and the decision was made to proceed with ASA, which led to significant improvement in the LVOT gradient pressures and the patient being able to tolerate his dialysis sessions.
Copyright © 2024, Girgis et al.
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