Search Results (54)

Background: Carpal tunnel syndrome (CTS) has emerged as an early indicator of cardiac amyloidosis (CA) caused by transthyretin-associated (ATTR) mutations, possibly linked to adverse cardiovascular outcomes. This case series examines the relationship between idiopathic CTS and CA imaging diagnosis. Methods: Twenty-two patients from the cross-sectional study CarPoS (NCT05409833) were included. These patients underwent physical evaluation, laboratory exams, electrocardiography, echocardiography, cardiac magnetic resonance (CMR) imaging, and scintigraphy with ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid. Results: Four of the twenty-two patients included had ATTR cardiomyopathy. These patients presented left-ventricle hypertrophy and signs of infiltrative cardiomyopathy in echocardiograms and late gadolinium enhancement in CMR images without having any cardiovascular symptoms. Conclusions: Our findings suggest a high prevalence of CA in patients with bilateral idiopathic CTS, highlighting the importance of screening for CA in patients with CTS. Early detection could significantly impact patient prognosis, underscoring the need for further research into diagnostic and therapeutic strategies. Full article

Cardiac amyloidosis (CA), an infiltrative restrictive cardiomyopathy, is a frequently underrecognized etiology of diastolic heart failure (HF). This study aimed to evaluate inpatient outcomes among patients hospitalized with decompensated diastolic HF with and without a secondary diagnosis of amyloidosis, utilizing data from the National Inpatient Sample (2018–2021). Among 2,444,699 patients hospitalized for decompensated diastolic HF, 9205 (0.3%) had a documented secondary diagnosis of amyloidosis. After 1:1 propensity-score matching, 1841 patients in each group were analyzed. Multivariate logistic regression revealed that the presence of amyloidosis was associated with significantly higher odds of in-hospital mortality (4.0% vs. 2.7%), cardiogenic shock (5.4% vs. 2.4%), acute kidney injury (28.3% vs. 22.0%), ventricular tachycardia (12.4% vs. 6.0%), and acute myocardial injury (9.5% vs. 6.0%) (all p < 0.05). Additionally, patients with amyloidosis had a longer mean length of stay (7.1 vs. 5.7 days) and higher mean hospitalization costs ($85,594 vs. $48,484, p < 0.05). Although the overall incidence of acute myocardial injury was elevated, subgroup analysis of ST-elevation and non–ST-elevation myocardial infarction revealed no significant differences. These findings underscore the considerable clinical and economic burden of amyloidosis in patients hospitalized with decompensated diastolic heart failure. Full article

Introduction: Hereditary transthyretin amyloidosis (ATTRv) is a severe, multisystemic, autosomal dominant disease with variable penetrance caused by mutations in the TTR gene generating protein misfolding and accumulation of amyloid fibrils. The diagnosis is usually challenging because ATTRv may initially manifest with nonspecific multisystemic symptoms. Conversely, an early diagnosis is needed to start timely appropriate therapy. Hence, screening models have been proposed to improve ATTRv diagnosis. In this study, we propose a genetic screening model based on predefined “red flags” followed by “cascading screening” on first-degree relatives of patients who tested positive. Materials and methods: After obtaining written informed consent, genetic testing on salivary swabs was performed in individuals who met at least two major red flags for ATTRv (age > 65 years old, progressive sensory or sensorimotor neuropathy not responsive to steroids or immunomodulant therapies, recent and unexplained weight loss associated with gastrointestinal signs and symptoms, diagnosis of cardiac amyloidosis, bilateral or relapsing carpal tunnel syndrome, unexplained autonomic dysfunction) or one major flag and two minor flags (family history of neuropathy, ambulation disorders or cardiopathy, sudden cardiac death, a bedridden, wheelchaired patient without specific diagnosis excluding upper motor neuron diseases, infections, juvenile cardiac disease, ocular disorders, lumbar spine stenosis, biceps tendon rupture). Results: In the first screening phase, 29 suspected cases (individuals meeting at least two major red flags or one major red flag and two minor red flags) underwent genetic testing. One patient (3.5%) was diagnosed with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN), carrying the Phe64Leu mutation. Then, cascade screening allowed for early recognition of two additional individuals (two pre-symptomatic carriers) among two first-degree relatives (100%). The identified patient was a 72-year-old man who had a family history of both cardiopathy, neuropathy, and a diagnosis of juvenile cardiac disease and progressive sensorimotor neuropathy unresponsive to steroids or immunomodulant therapies. Conclusions: ATTRv is a progressive and often fatal disease that should be promptly diagnosed and treated to stop progression and reduce mortality. Systematic screening for ATTRv yielded increased recognition of the disease in our neurological clinic. A focused approach for the screening of ATTRv-PN could lead to an earlier diagnosis and identification of asymptomatic carriers, enabling timely intervention through close clinical monitoring and early treatment initiation at symptom onset. Full article

Amyloidosis is an infiltrative disease that may cause cardiomyopathy if the precursor protein that misfolds and forms the amyloid is transthyretic or plasma abnormal light chains. Transthyretin amyloid cardiomyopathy has to be diagnosed timely and accurately since there are specific treatment options to support the patients. Multimodality imaging including electrocardiography, echocardiography with strain imaging and cardiac magnetic resonance applying late gadolinium enhancement imaging, native T1 mapping and extracellular volume, raise a high suspicion of the disease and bone scintigraphy set the diagnosis even without the need of biopsy. However, the morbidity and mortality remain high and the need for risk stratification and assessment of the response to treatment are of paramount importance. Cardiac imaging biomarkers offer a thoughtful insight into the prognosis of these patients at diagnosis and after treatment. The current narrative review aims to enlighten the use of multimodality cardiac imaging in transthyretic amyloid cardiomyopathy throughout the disease pathogenesis and evolution from diagnosis to prognosis and response to treatment in a personalized manner. Full article

Background: Cardiomyopathies are a significant cause of heart failure, arrhythmia, and cardiac morbidity in the general population. Cardiovascular magnetic resonance (CMR) is a valuable tool for the diagnostic work-up of patients with acute cardiac events. Objectives: This study evaluated the diagnostic value of CMR and the yield of cardiomyopathies in hospitalized cardiac patients with acute presentation. Methods: A retrospective analysis was conducted with 535 consecutive hospitalized patients who underwent CMR at Hippokration Hospital, Athens, Greece, to identify a subset of scans performed on an urgent basis of hospitalized patients. Demographic data, causes of admission, CMR findings, and plasma cardiac biomarkers (hs-Troponin I, NT-proBNP, and CRP) were systematically recorded. Results: Out of the initial 535 CMR scans evaluated, a further analysis was conducted with 104 patients who were in hospital and underwent CMR on an urgent basis. From the total population of hospitalized patients, 33% had CMR findings indicative of underlying cardiomyopathy, with dilated cardiomyopathy being the most common subtype (36%), followed by arrhythmogenic cardiomyopathy (27%), hypertrophic cardiomyopathy (15%), or other subtypes (e.g., cardiac amyloidosis, sarcoidosis, endomyocardial fibrosis, EGPA, or unclassified). CMR led to the reclassification of the initial diagnosis into that of underlying cardiomyopathy in 32% of cases. The highest reclassification rate was observed within the subgroup with heart failure (71%), followed by that of acute myocardial infarction/ischemic heart disease (24%) and myocarditis (22%). Conclusions: CMR imaging effectively contributed to the differential diagnosis of hospitalized patients with acute cardiac events that remained without a definitive diagnosis after their initial work-up and uncovered underlying cardiomyopathy in almost one-third of this cohort. Full article

Background/Objectives: Cardiac amyloidosis (CA) is associated with amyloid infiltration of the extra-cardiac tissue, which may occur in the early stages of the disease. This study evaluates the diagnostic utility of thoracic fat pad biopsy obtained during a pacemaker or ICD implantation as an alternative to the standard diagnostic criteria for systemic amyloidosis. Methods: This exploratory, retrospective study included 27 patients with suspected or diagnosed CA who underwent pacemaker or defibrillator therapy. Results: Of these, 16 patients were confirmed to have CA (15 with technetium-labeled bisphosphonate bone scintigraphy and 1 with protein electrophoresis and echocardiographic findings) while 11 were confirmed to be CA-negative. The thoracic fat pad biopsy demonstrated a specificity of 100% but a sensitivity of only 31%. Among patients with transthyretin (ATTR)-CA, the sensitivity remained similarly low, at 27%. These results are consistent with prior findings on abdominal fat pad biopsy in ATTR-CA, highlighting the limited diagnostic yield of this method. Conclusions: Thoracic fat pad biopsy cannot be recommended as a standard diagnostic tool for CA, particularly in ATTR-CA, due to its poor sensitivity. However, in AL (amyloid light-chain) amyloidosis, this minimally invasive procedure may aid diagnosis without additional invasive interventions. Full article

Transthyretin amyloidosis (ATTR amyloidosis) is characterized by the buildup of amyloid protein in organs like the gut and the heart. As a result, hypoperfusion, edema, and dysautonomia cause an imbalance in the gut microbiome. We aimed to identify the gut microbiome composition in ATTR amyloidosis patients with and without heart involvement, as well in controls. Sixty participants were divided into three groups: 20 with ATTR amyloidosis and heart involvement (G1), 19 with ATTR amyloidosis but no heart disease (G2), and 21 controls (G3). The microbiome profiles were obtained through 16S rRNA gene sequencing. Additional evaluations included a clinical questionnaire, echocardiogram, six-minute walk tests, troponin, BNP, and genotype analysis. Compared to G3, G1, and G2 groups had different levels of Streptococcus, Lachnospiraceae, and Sellimonas, while the controls showed a higher relative abundance of Methanosphaera. Streptococcus was linked to higher troponin levels. Lachnospiraceae was associated with lower BNP levels and smaller left atrium volumes. Sellimonas was associated with a higher intestinal symptom score, while Methanosphaera with a lower symptom score. ATTR amyloidosis patients have a different intestinal microbiome profile compared to the control group. There were correlations with genotype, gastrointestinal symptoms, heart failure biomarkers, echocardiographic parameters, and the six-minute walk test. Full article

Background: Hereditary transthyretin amyloidosis (ATTRv) is an autosomal-dominant systemic disease, where amyloid fibrils accumulate especially in the peripheral and autonomic nervous systems and in the heart. The aim of the present work was to outline the follow-up and type of management received by asymptomatic carriers (ACs) and Coutinho stage 1 ATTRv patients in Spain. Methods: A cross-sectional, non-interventional study was conducted throughout seven experienced hospitals in Spain. A total of 86 ACs without neurological symptoms and 19 Coutinho stage 1 ATTRv patients diagnosed 12 months before their enrollment were included. Clinical and demographic data, red flags, and neurological and cardiological evaluations were gathered. In addition, site variables were collected from four centers to describe the clinical management of ATTRv. Results: ATTRv clinical management varied depending on the center setting but was primarily overseen by neurology and internal medicine, which were responsible for the holistic follow-up of ACs and patients. Routinely, neurologists, neurophysiologists, cardiologists, and internal medicine conducted the follow-up. Specialties involved in initial AC assessment were neurophysiologists and cardiologists in 100% of cases, neurologists (75%), internists and geneticists (50%), and ophthalmologists (25%). A review of the medical tests performed proved an exhaustive management of the study population. Stable patients were followed up every 6 months, while those under evolution were monitored every 3–6 months. The frequency of monitoring of ACs was annual, and carriers classified with doubtful disease onset were visited every 3–6 months. Conclusions: The EMPATIa study provides valuable insights into the management of ATTRv in a real-world clinical setting in highly experienced hospitals in Spain. It demonstrates that multidisciplinary practice and enhanced disease awareness may lead to a reduction in diagnostic delay. Full article

There are comorbidities and complications in atopic dermatitis and psoriasis that often occur after the appearance of skin inflammation. Statistically, data show that patients with psoriasis and atopic dermatitis have a shorter life expectancy than patients without psoriatic dermatitis, due to the occurrence of arteriosclerosis, myocardial infarction, and cerebral infarction. Many types of skin inflammation are treated with various antibody preparations, and marked improvement in patients’ quality of life can be achieved. The next theme is to understand the pathogenesis of arteriosclerosis, myocardial infarction, stroke, and other complications associated with dermatitis and to find treatments and drugs to reduce their occurrence. The skin, a crucial immune organ, generates large amounts of inflammatory cytokines in response to various stimuli, leading to systemic inflammation and potential damage to internal organs. The link between inflammatory skin conditions like psoriasis and atopic dermatitis with serious health complications such as vascular disorders and systemic amyloidosis has been increasingly recognized. In psoriasis, biological treatments targeting Interleukin (IL)-17A, a key cytokine, have shown promise in reducing cardiovascular risks. Recent developments include treatments that target both IL-17A and IL-17F in the psoriasis field, though each cytokine’s impact on internal organ damage is still under debate. Among visceral complications secondary to dermatitis, systemic amyloidosis and atherosclerosis have been reported to be controlled by suppressing IL-17 in the early stages of dermatitis. Still, it remains unclear whether suppressing IL-17 prevents organ damage in the late stages of persistent severe dermatitis. A study using a long-lasting dermatitis mouse model that overexpressed human caspase-1 in keratinocytes (Kcasp1Tg) investigated the effects of deleting IL-17A and IL-17F on visceral complications. Cross-mating Kcasp1Tg with IL-17A-, IL-17F-, and IL-17AF-deficient mice assessed the skin and visceral organs histologically, and RT-PCR analysis of aortic sclerosis markers was performed. Despite less improvement in dermatitis, deletion of IL-17A in Kcasp1Tg mice showed promising results in reducing multiple organ amyloidosis. On the other hand, the effect was observed in both IL-17A and IL-17F deleted mice for aortic sclerosis. The inhibition of IL-17A and IL-17F was suggested to reduce the risk of developing comorbidities in internal organs. IL-17A and IL-17F were found to act similarly or produce very different results, depending on the organ. Full article

Background: Hereditary transthyretin-related amyloidosis is a clinically heterogeneous autosomal dominant disease caused by pathogenic variants in the TTR gene (hATTR amyloidosis). Objective: The current study describes the demographic, clinical, and genetic characteristics of patients with suspected hATTR amyloidosis. Methods: This study is part of the “Hereditary transthyretin-related amyloidosis and longitudinal monitoring of TTR-positive patients” (TRAMmoniTTR) study. This study included 3167 participants, along with their clinical details. Principal component (PC) analysis was used to analyze their clinical symptomatology. Next-generation sequencing of the TTR gene was performed and genotype–phenotype relationships were investigated. We compared the demographic and clinical characteristics using the principal components (PCs) and also compared participants with and without the TTR pathogenic variants. Results: We identified five main clinical phenotypes out of 22 single symptoms that explained 49% of the variation. The first two PCs referred to polyneuropathy and cardiomyopathy. We found significant differences between gender and PC-polyneuropathy and PC-cardiomyopathy, with male over-representation in the higher quantiles of PC-polyneuropathy and male under-representation in the lowest quantiles of PC-cardiomyopathy. We identified 92 participants with hATTR (3%), exhibiting 17 unique heterozygous TTR variants. The p.Val50Met variant was the most frequent. Furthermore, 503 participants (20%) were identified with ATTR and no relevant TTR variants (ATTRwt). We detected significant differences between the ATTRwt and hATTR groups, with male gender predominance in only the ATTRwt group and a positive family history of polyneuropathy and/or cardiomyopathy among the hATTR participants. Conclusions: The current clinical and genetic characterization of this cohort serves as a foundation for further longitudinal monitoring and assessment. Full article

Background: In recent years, many advances have been made in the treatment of hereditary transthyretin amyloidosis (ATTRv). Patisiran is a small-interfering RNA used to treat ATTRv with only polyneuropathy or polyneuropathy and cardiomyopathy. The aim of our study was to assess the effect of patisiran on cardiac function in ATTRv patients using speckle tracking echocardiography (STE) analysis. Methods: A single-center prospective study was performed enrolling 21 patients with ATTRv (11 M—52% of the population; 10 F—48% of the population; median age 66 ± 8.4 years old). A total of 7 patients had cardiac amyloidosis and polyneuropathy, and 14 patients had only polyneuropathy without cardiac involvement. Cardiological evaluation including electrocardiograms, echocardiography with STE, and assessment of myocardial work parameters was performed in all patients before starting patisiran and after 9–18 months. Functional capacity was assessed using the 6 min walk test; quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Results: We did not find a significant difference in gender prevalence of ATTR amyloidosis in all of the population (p-value 0.79), but we found that cardiac amyloidosis significantly predominated in the male sex compared to patients with only neuropathy. In all patients, we found a slight improvement in functional capacity and quality of life. We did not find significant changes in left ventricular ejection fraction (LVEF), but we found a significant improvement in left ventricular global longitudinal strain (GLS), global work waste (GWW), and global work efficiency (GWE), especially in patients with cardiac amyloidosis; E/e’ average and left atrial stiffness also improved significantly in patients with cardiac amyloidosis. Conclusions: Our study confirms a positive effect of patisiran on cardiac function, particularly the absence of signs of subclinical deterioration as detected by very sensitive STE parameters such as GLS, MW, and atrial stiffness during follow up in patients treated with patisiran. Full article

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. Full article

Background: The presence of a relative apical sparing (RAS) echocardiographic strain pattern raises a suspicion of underlying cardiac amyloidosis (CA). However, it is also increasingly observed in patients with aortic stenosis (AS). We aimed to evaluate the prevalence, dynamics, and clinical characteristics of the RAS strain pattern in severe AS patients who had been referred for surgical aortic valve replacement (SAVR). Methods: A total of 77 patients with severe AS and without CA were included with a mean age of 70 (62–73) years, 58% female, a mean aortic valve area index of 0.45 ± 0.1 cm²/m², and a mean gradient of 54.9 (45–70) mmHg. Results: An RAS strain pattern was detected in 14 (18%) patients. RAS-positive patients had a significantly higher LV mass index (125 ± 28 g/m² vs. 91 ± 32, p = 0.001), a lower LV ejection fraction (62 ± 12 vs. 68 ± 13, p = 0.040), and lower global longitudinal strain (–14.9 ± 3 vs. –18.7 ± 5%, p = 0.002). RAS strain pattern-positive patients also had higher B-type natriuretic peptide (409 (161–961) vs. 119 (66–245) pg/L, p = 0.032) and high-sensitivity troponin I (15 (13–29) vs. 9 (5–18) pg/L, p = 0.026) levels. Detection of an RAS strain pattern was strongly associated with increased LV mass index (OR 1.03, 95% CI 1.01–1.06, p < 0.001). The RAS strain pattern had resolved in all patients by 3 months after SAVR. Conclusions: Our findings suggest that the RAS strain pattern can be present in patients with severe AS without evidence of CA. The presence of an RAS strain pattern is associated with adverse LV remodeling, and it resolves after SAVR. Full article

Background and Objectives: Cardiac magnetic resonance (CMR) imaging has become an essential instrument in the study of cardiomyopathies; it has recently been integrated into the diagnostic workflow for cardiac amyloidosis (CA) with remarkable results. An additional emerging role is the stratification of the arrhythmogenic risk by scar analysis and the possibility of merging these data with electro-anatomical maps. This is made possible by using a software (ADAS 3D, Galgo Medical, Barcelona, Spain) able to provide 3D heart models by detecting fibrosis along the whole thickness of the myocardial walls. Little is known regarding the applications of this software in the wide spectrum of cardiomyopathies and the potential benefits have yet to be discovered. In this study, we tried to apply the ADAS 3D in the context of CA. Materials and Methods: This study was a retrospectively analysis of consecutive CMR imaging of patients affected by CA that were treated in our center (Marche University Hospital). Wherever possible, the data were processed with the ADAS 3D software and analyzed for a correlation between the morphometric parameters and follow-up events. The outcome was a composite of all-cause mortality, unplanned cardiovascular hospitalizations, sustained ventricular arrhythmias (VAs), permanent reduction in left ventricular ejection fraction, and pacemaker implantation. The secondary outcomes were the need for a pacemaker implantation and sustained VAs. Results: A total of 14 patients were deemed eligible for the software analysis: 8 patients with wild type transthyretin CA, 5 with light chain CA, and 1 with transthyretin hereditary CA. The vast majority of imaging features was not related to the composite outcome, but atrial wall thickening displayed a significant association with both the primary (p = 0.003) and the secondary outcome of pacemaker implantation (p = 0.003). The software was able to differentiate between core zones and border zones of scars, with the latter being the most extensively represented in all patients. Interestingly, in a huge percentage of CMR images, the software identified the highest degree of core zone fibrosis among the epicardial layers and, in those patients, we found a higher incidence of the primary outcome, without reaching statistical significance (p = 0.18). Channels were found in the scar zones in a substantial percentage of patients without a clear correlation with follow-up events. Conclusions: CMR imaging plays a pivotal role in cardiovascular diagnostics. Our analysis shows the feasibility and applicability of such instrument for all types of CA. We could not only differentiate between different layers of scars, but we were also able to identify the presence of fibrosis channels among the different scar zones. None of the data derived from the ADAS 3D software seemed to be related to cardiac events in the follow-up, but this might be imputable to the restricted number of patients enrolled in the study. Full article

Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. There is a need for an early and sensitive blood biomarker for polyneuropathy, and this systematic review provides an overview on the value of NfL in the early detection of neuropathy, central nervous system involvement, the monitoring of neuropathy progression, and treatment effects in systemic amyloidosis. A literature search in PubMed, Embase, and Web of Science was performed on 14 February 2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene-variant (TTRv) carriers. Only studies containing original data were included. Included were thirteen full-text articles and five abstracts describing 1604 participants: 298 controls and 1306 TTRv carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following the initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease-process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has the potential to be used for the early detection of neuropathy, monitoring treatment effects, and monitoring disease progression in patients with systemic amyloidosis. Full article