Amyloidosis Research Articles

Helical superstructures between amyloid and collagen in cardiac fibrils from a patient with AL amyloidosis

Systemic light chain (LC) amyloidosis (AL) is a disease where organs are damaged by an overload of a misfolded patient-specific antibody-derived LC, secreted by an abnormal B cell clone. The high LC concentration in the blood leads to amyloid deposition at organ sites. Indeed, cryogenic electron microscopy (cryo-EM) has revealed unique amyloid folds for heart-derived fibrils taken from different patients. Here, we present the cryo-EM structure of heart-derived AL amyloid (AL59) from another patient with severe cardiac involvement. The double-layered structure displays a u-shaped core that is closed by a β-arc lid and extended by a straight tail. Noteworthy, the fibril harbours an extended constant domain fragment, thus ruling out the variable domain as sole amyloid building block. Surprisingly, the fibrils were abundantly concatenated with a proteinaceous polymer, here identified as collagen VI (COLVI) by immuno-electron microscopy (IEM) and mass-spectrometry. Cryogenic electron tomography (cryo-ET) showed how COLVI wraps around the amyloid forming a helical superstructure, likely stabilizing and protecting the fibrils from clearance. Thus, here we report structural evidence of interactions between amyloid and collagen, potentially signifying a distinct pathophysiological mechanism of amyloid deposits.

Skeletal muscle involvement in systemic amyloidosis is often overlooked.

Systemic amyloidosis is a condition in which misfolded amyloid fibrils are deposited within tissues. Amyloid myopathy is a rare manifestation of systemic amyloidosis. However, whether skeletal muscle involvement is underestimated and whether such deposition guarantees clinical and pathological myopathic features remain to be investigated. We retrospectively reviewed patients with systemic amyloidosis, in whom skeletal muscle biopsies were performed at our centre between January 2018 and June 2023. In total, 28 patients with suspected systemic amyloidosis were included. Among these, 21 presented with cardiomyopathy but lacked myopathic symptoms. The clinical and pathological data of these patients were further analysed. The amyloid type was confirmed by immunohistochemistry. Twenty-eight patients with suspected systemic amyloidosis underwent muscle biopsy. Amyloid deposition in the skeletal muscle was confirmed in 24 patients, including 22 with light-chain amyloidosis (AL) and two with transthyretin amyloidosis (ATTR). Among the 24 patients, seven presented with muscle weakness and decreased muscle strength (Group 1, symptomatic myopathy), whereas the remaining 17 exhibited normal muscle strength (Group 2, asymptomatic myopathy). Group 1 included four patients with AL-λ, one with AL-κ and two with ATTR. Group 2 included 15 patients with AL-λ and two patients with AL-κ. In Group 1, six patients exhibited neuropathy, whereas only one patient in Group 2 presented with subclinical neuropathy on nerve conduction studies. Amyloid deposition in the interstitium was the most obvious change, observed in all 24 patients. Neuropathic changes, including denervation atrophy and muscle fibre grouping, were also common. Except for type 2 fibre atrophy, the other myopathic changes were mild and nonspecific. No sarcolemmal disruption was observed. Immunohistochemical analysis revealed marked positivity for MAC and MHC1 expression in the regions with amyloid deposits. Clinicopathological analysis revealed no significant differences in the extent of muscular amyloid deposition between the two groups. Nevertheless, patients in Group 1 displayed more pronounced neurogenic atrophy on skeletal muscle biopsies. Our study indicates that amyloid deposition in skeletal muscle is commonly observed but rarely causes symptomatic myopathy in systemic amyloidosis.

Enhanced stabilisation and reduced fibril forming potential of an amyloidogenic light chain using a variable heavy domain to mimic the homodimer complex.

Light chain amyloidosis (AL), is classified as a plasma cell dyscrasia, whereby a mutant plasma cell multiplies uncontrollably and secretes enormous amounts of immunoglobulin-free light chain (FLC) fragments. These FLCs undergo a process of misfolding and aggregation into amyloid fibrils, that can cause irreversible system-wide damage. Current treatments that focus on depleting the underlying plasma cell clone are often poorly tolerated, particularly in patients with severe cardiac involvement, meaning patient prognosis is poor. An alternative treatment approach currently being explored is the inhibition of FLC aggregation by stabilisation of the native conformer. Here, we aimed to identify and characterise antibody fragments that target FLC domains and promote their stabilisation. Using phage-display screening methods, we identified a variable heavy (VH) domain, termed VH1, targeted towards the FLC. Using differential scanning fluorimetry and surface plasmon resonance, VH1 was characterised to bind and kinetically stabilise an amyloidogenic FLC, whereby a > 5.5 °C increase in thermal stability was noted. This improved stability corresponded to the inhibition of fibril formation, where 10 : 1 LC : VH1 concentration reduced aggregation to baseline levels. X-ray crystallographic structures of the LC : VH1 complex at atomic resolution revealed binding in a 1 : 1 ratio, mimicking the dimeric antigen binding sites of the native immunoglobulin molecule and the native LC homodimer.

Delayed identification of monoclonal protein is associated with early death in isolated cardiac AL amyloidosis

Background Early identification of immunoglobulin light-chain amyloidosis (AL) is crucial due to its rapid progression. Monoclonal light-chain (M-LC) testing is the first step in the diagnostic workup for patients with suspected cardiac amyloidosis (CA). We aimed to determine whether the time interval between the first CA suspicion and M-LC testing can be related to AL amyloidosis survival outcomes. Methods All patients (n = 94) with isolated cardiac AL amyloidosis diagnosed at our center between 2016 and 2020 were included. Those with pre-existing known monoclonal protein (monoclonal gammopathy of undetermined significance or smoldering multiple myeloma) were excluded. Time intervals to diagnostic tests and diagnosis were calculated and assessed for their survival prediction ability. Results The time interval between first CA suspicion (on echocardiography) and M-LC testing correlated with early mortality, and the best cutoff predicting survival, was 6 weeks. The 26 patients (∼28% of entire cohort) who underwent M-LC-studies >6 weeks after first suspicion more frequently presented Mayo stage IIIb (65% vs. 35%, p = .008), showing poorer overall survival than those (n = 68, 72%) referred for early M-LC studies (median 3 vs. 14 months, p = .039). Conclusions Monoclonal protein testing should be the first-step in the diagnostic workup for patients with echocardiographic/other instrumental red flags raising CA suspicion.

Internalisation of immunoglobulin light chains by cardiomyocytes in AL amyloidosis: what can biopsies tell us?

Background Cardiac involvement in systemic light chain amyloidosis (AL) leads to chronic heart failure and is a major prognosis factor. Severe cellular defects are provoked in cardiac cells by tissue-deposited amyloid fibrils of misfolded free immunoglobulin light chains (LCs) and their prefibrillar oligomeric precursors. Objective Understanding the molecular mechanisms behind cardiac cell cytotoxicity is necessary to progress in therapy and to improve patient management. One key question is how extracellularly deposited molecules exert their toxic action inside cardiac cells. Here we searched for direct evidence of amyloid LC uptake by cardiomyocytes in patient biopsies. Methods We immunolocalized LCs in cardiac biopsies from four AL cardiac amyloidosis patients and analysed histopathological images by high resolution confocal microscopy and 3D image reconstruction. Results We show, for the first time directly in patient tissue, the presence of LCs inside cardiomyocytes, and report their proximity to nuclei and to caveolin-3-rich areas. Our observations point to macropinocytosis as a probable mechanism of LC uptake. Conclusions Internalisation of LCs occurs in patient cardiomyocytes. This event could have important consequences for the pathogenesis of the cardiac disease by enabling interactions between amyloid molecules and cellular organelles inducing specific signalling pathways, and might bring new insight regarding treatment.

Response rates to second-line treatment with daratumumab bortezomib dexamethasone (DVD) in relapsed/refractory light chain amyloidosis (AL) after initial Bortezomib-based regime.

Bortezomib is regularly used as frontline therapy for systemic AL amyloidosis. We assess the efficacy of second-line daratumumab-bortezomib-dexamethasone (DVD) in AL amyloidosis in bortezomib-exposed patients. A total of 116 patients treated with second-line DVD were identified from a prospective observational study of newly diagnosed AL amyloidosis (ALchemy). DVD was initiated in both the relapsed setting or where there was an inadequate response defined as very good partial response (VGPR) or VGPR with organ progression/lack of organ improvement. A complete response (CR)/VGPR to second-line DVD was achieved in 81 (69.8%) patients. A CR/VGPR was achieved in 67 (79.7%) in those who achieved a VGPR/CR to first line versus 14/32 (43.8%) in those who did not. Where DVD was initiated due to an inadequate response to first line (vs. at relapse), the median event-free survival (EFS) was 18 vs. 34 months (p = 0.002). If a CR/VGPR was achieved to DVD, the 2-year EFS was still lower in those with prior inadequate response 54% vs. 66% (p = 0.062). DVD is an efficacious second-line treatment in systemic AL amyloidosis in a bortezomib-exposed population. However, the response to DVD is poorer in those with an inadequate response to first-line bortezomib.

Bristol Cup PostersP001 A descriptive, observational and cross-sectional study of clinicoepidemiological, dermoscopic and histopathological aspects of primary localized cutaneous amyloidosis and its effect on the quality of life of the patient

Bristol Cup PostersP001 A descriptive, observational and cross-sectional study of clinicoepidemiological, dermoscopic and histopathological aspects of primary localized cutaneous amyloidosis and its effect on the quality of life of the patient

Parametric mapping using cardiovascular magnetic resonance for the differentiation of light chain amyloidosis and transthyretin-related amyloidosis.

To evaluate different cardiovascular magnetic resonance (CMR) parameters for the differentiation of light chain amyloidosis (AL) and transthyretin-related amyloidosis (ATTR). In total, 75 patients, 53 with cardiac amyloidosis (20 patients with AL (66±12 years, 14 males [70%]) and 33 patients with ATTR (78±5 years, 28 males [88%])) were retrospectively analyzed regarding CMR parameters such as T1 and T2 mapping, extracellular volume (ECV), and late gadolinium enhancement (LGE) distribution patterns, and myocardial strain, and compared to a control cohort with other causes of left ventricular hypertrophy (LVH; 22 patients (53±16 years, 17 males [85%])). One way-ANOVA and receiver operating characteristic analysis were used for statistical analysis. ECV was the single best parameter to differentiate between cardiac amyloidosis and controls (area under the curve [AUC]: 0.97, 95% confidence intervals [CI]: 0.89-0.99, p<.0001, cutoff: >30%). T2 mapping was the best single parameter to differentiate between AL and ATTR amyloidosis (AL: 63±4 ms, ATTR: 58±2 ms, p<.001, AUC: 0.86, 95% CI: 0.74-0.94, cutoff: >61 ms). Subendocardial LGE was predominantly observed in AL patients (10/20 [50%] vs. 5/33 [15%]; p=.002). Transmural LGE was predominantly observed in ATTR patients (23/33 [70%] vs. 2/20 [10%]; p<.001). The diagnostic performance of T2 mapping to differentiate between AL and ATTR amyloidosis was further increased with the inclusion of LGE patterns (AUC: 0.96, 95% CI: 0.86-0.99]; p=.05). ECV differentiates cardiac amyloidosis from other causes of LVH. T2 mapping combined with LGE differentiates AL from ATTR amyloidosis with high accuracy on a patient level.

A novel mutation in the transthyretin gene in amyloidosis: A cluster case report in Vietnam

Transthyretin amyloidosis (ATTR) is a slowly progressive condition characterised by the abnormal accumulation of a protein called amyloid in the body’s organs and tissues. There are three main subtypes of amyloidosis (AL), including primary or AL, secondary or AA AL, and hereditary or familial AL. Hereditary AL, which is less common, is caused by an autosomal-dominant mutation, most frequently in the transthyretin (TTR) gene, and has a more favourable prognosis. We report the case of a 51-year-old Vietnamese male who presented with severe dizziness, fainting episodes, low BMI, slow heart rate, and a blood pressure of 60/40 mmHg. The patient had a history of diges-tive disorders, weakness, and pain in the legs even after disc spine surgery. All symptoms onset occurred at 43 years old. A pathogenic mutation in the TTR gene c.209G&gt;T was confirmed in the patient and 7 out of 15 individuals in his extended family. This is the first case reported in Vietnam diagnosing a new variant of TTR causing typical AL. Based on this study, we conclude that the TTR variant c.209G&gt;T is a pathogenic gene. This study also emphasises the need for increased knowledge regarding AL associated with this pathogenic variant. However, further extensive research is required to provide a comprehensive understanding of the pathogenesis of TTR in the future.

Penile nodules and ulcer.

Primary amyloidosis of the penis is an uncommon variant of localized amyloidosis. The clinical presentation is variable, ranging from waxy or infiltrated nodules or plaques typical for nodular amyloidosis, to hyperpigmented macules in macular amyloidosis, and papules or plaques in lichen amyloidosis. Amyloidosis should be suspected and Congo red staining performed in cases of clinically uncommon penile masses or ulcers, or histologically atypical hyalinization.

#2724 Renal amyloidosis cohort registry in our health area

Abstract Background and Aims Renal amyloidosis is the pathological phenomenon of amyloid deposition in the kidney with marked differences in renal function impairment, proteinuria, need for renal replacement therapy (RRT) and exitus, depending on the protein involved. Light chain amyloidosis (AL) and serum protein A (AA) amyloidosis are the most common. Typical symptoms are severe proteinuria, nephrotic syndrome, and end-stage chronic kidney disease (ESRD). Method Retrospective study of a cohort of patients with renal amyloidosis. Data extracted from the biopsy registry of the HUVM Nephrology Service (2013-2022). We collected demographic, clinical, analytical, histological and clinical outcome variables (RTT, Exitus). Results are analyzed using Mayo Clinic staging criteria. Results 19 patients with a mean age of 63.4a; 57.9% male. Mean laboratory values at diagnosis: creatinine (Cr) 1.56 mg/dl and proteinuria 3.9 g/24 h. Abdominal fat biopsy in 13 cases; 3 (23%) tested positive. Comparative analysis of AL vs non-AL forms, Cr values (1.14 vs 2.27 mg/dl respectively) (p=0.57) differed. Proteinuria according to the histological location of the amyloid: 4.6 g/24 h in glomerular involvement vs. 0.3 g/24 h in those who did not present it (p&amp;lt;0.05). 31.6% required RTT with a mean onset time of 250.6 d from biopsy. Exitus of 21.1%: average time of 426.5 d. (See analysis in attached table). Conclusion We did not observe significant deterioration of renal function, which is greater in non-AL forms of amyloidosis. Fat biopsy was less cost-effective than reported in the literature. Significantly lower levels of proteinuria were found in the amyloidosis group without glomerular involvement. In our series, the prognostic capacity associated with the MAYO staging was confirmed.

Localized Urinary Bladder Amyloidosis as Urothelial Cancer Mimicker.

Localized amyloidosis of the bladder is rare and often mimics bladder malignancy. It is typically associated with the extracellular deposition of monoclonal light chains, either κ or λ. The cause is unknown, but it is thought to be due to chronic inflammation/cystitis. To highlight the importance of localized urinary bladder amyloidosis as a rare mimicker of urothelial malignancy and elucidate its clinical, histopathologic, and cytopathologic manifestations. Cases of urinary bladder amyloidosis diagnosed during 2000-2023 were retrieved retrospectively from pathology archives. Electronic medical records, including cystoscopy findings and pathology slides including Congo red stain, were reviewed. Here we present 6 patients with localized urinary bladder amyloidosis. Four of the 6 patients were women, with ages ranging from 46 to 69 years, and a mean age of 58 years. Five of 6 patients presented with hematuria, while in 1 patient, bladder amyloidosis was discovered incidentally. Cystoscopy findings invariably were concerning for malignancy, with raised erythema in 5 patients and fungating mass protruding into the bladder lumen in 1 patient. Bladder biopsies and urine cytology were negative for malignancy in all cases. Congo red-positive amyloid deposits involved lamina propria with sparing of the detrusor muscle. In 5 cases, the deposits were typed as derived from the λ light chain, whereas no information was available for 1 patient. Subsequent clinical workup ruled out systemic amyloidosis. These cases of urinary bladder amyloidosis highlight the importance of considering rare amyloidosis in the differential diagnosis of hematuria and cystoscopy with a lesion mimicking malignancy.

Acute Coronary Syndrome (ACS) with ST-Segment Elevation Revealing Cardiac Amyloidosis: A Case Report and Literature Review

Cardiac Amyloidosis (CA) is an infiltrative cardiomyopathy characterized by the accumulation of fibrillar proteins in the myocardium. The deposition of these proteins disrupts the structure and function of the heart, leading to thickened walls, increased myocardial mass, diastolic dysfunction, and altered myocardial contraction, ultimately causing progressive heart failure. We report the case of a 65-year-old patient, S.L., admitted to our service with Acute Coronary Syndrome (ACS) with a posterior extended ST-segment elevation, Killip class I, semi-recent. She is hypertensive and diabetic; she previously underwent surgery for chronic constrictive pericarditis, presumed to be of tuberculous origin, and was treated accordingly. The echocardiogram revealed a hypokinetic left ventricle (LV), predominantly affecting the inferior, inferoseptal, and apical walls. The left and right atria were not dilated, and both ventricles were of normal size. Coronary angiography showed no significant anomalies. Cardiac MRI supported a diagnosis of localized amyloidosis. Through this case, we explore the various clinical forms of CA, referencing existing literature.

Clinicopathological Features of Amyloid Neuropathy: A Four Decade Experience

Background: Peripheral neuropathy is one of the manifestations of primary or familial amyloidosis. Published studies from India are limited. Materials and Methods: We reviewed the clinical and pathological features of amyloid neuropathy diagnosed at our Institute over the last 39 years. Results: Fifty-five cases of amyloid neuropathies were diagnosed between 1981 and 2019, constituting 0.28% of peripheral nerve biopsies (55/19,081). Age at presentation ranged from 24 to 81 years (mean—48 years) with male preponderance [M:F = 3.58:1]. Duration of symptoms at presentation varied from 3 months to 10 years (mean—2.31 years). Majority presented with small fiber neuropathy (85%). Pure sensory symptoms predominated in 23%, while 72% had sensorimotor neuropathy and 35.8% had autonomic involvement, with isolated autonomic failure in one patient. Amyloid neuropathy was clinically suspected in 22.6% of nonfamilial cases. Familial amyloid neuropathy was suspected in eight patients. Genetic testing detected ATTR and gelsolin mutation in one each of tested patients. Nerve biopsies revealed characteristic birefringent amyloid deposits stained mahogany brown by Congo red predominantly surrounding endoneurial microvessels (34.5%), also in perineurium and epineurium in 25.45% cases. Preferential loss of small diameter myelinated fibers was noted. Axonal degeneration or regeneration was conspicuously absent. Conclusion: Amyloid neuropathy is uncommon (0.28% of nerve biopsies in our series). Nerve biopsy is essential for the diagnosis. We report our experience of amyloid neuropathy and underscore the importance of making an assiduous search for amyloid deposits in the appropriate setting. Awareness of this entity is important for early diagnosis in the light of emerging therapeutic advances.

Outcomes of Modified Mayo Stage IIIa and IIIb Cardiac Light-Chain Amyloidosis: Real-World Experience in Clinical Characteristics and Treatment-67 Patients Multicenter Analysis.

Light-chain amyloidosis (AL) is a rare multisystem disorder characterized by the deposition of misfolded amyloid fibrils derived from monoclonal immunoglobulin light chains in various organs. One of the most common organs involved in AL is the heart, with 50-70% of patients clinically symptomatic at diagnosis. We conducted a multi-center, retrospective analysis of 67 patients diagnosed between July 2012 and August 2022 with the European 2012 modification of Mayo 2004 stage III cardiac AL. The most important factors identified in the univariate Cox analysis contributing to a longer OS included Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1, New York Heart Association functional classification (NYHA FC) ≤ 2, the use of autologous stem cell transplantation (ASCT) after induction treatment, achieving a hematological response (≥very good partial response) and cardiac (≥partial response) response after first-line treatment. The most important prognostic factors with the most significant impact on OS improvement in patients with modified Mayo stage III cardiac AL identified by multivariate Cox analysis are ECOG PS ≤ 1, NYHA FC ≤ 2, and achieving hematological response ≥ VGPR and cardiac response ≥ PR after first-line treatment.

Use of Bone Scintigraphy in The Diagnosis of Cardiac Amyloidosis

Cardiac amyloidosis is a rare and progressive condition caused by the buildup of amyloid in the heart. There are two common forms of cardiac amyloidosis: light-chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). The deposition of amyloid in the extracellular matrix of the myocardium leads to heart failure over time, and if left untreated, it can even be fatal. For this reason, early diagnosis is essential for both prognosis and improving patients' quality of life. Since cardiac amyloidosis is a potentially treatable condition, early diagnosis is key to improving patient survival and quality of life. There is now compelling evidence showing that nuclear imaging plays a fundamental role in the non-invasive diagnosis of transthyretin cardiac amyloidosis. Due to its high sensitivity and specificity, radiotracer compounds that target the bones are considered sufficient for establishing the diagnosis, avoiding the need for endomyocardial biopsy. In this study, we analyzed data obtained from examinations conducted on patients referred to the Cardiology Department of the "San Giovanni di Dio e Ruggi d'Aragona" University Hospital, who presented with suspected cardiac amyloidosis. These patients underwent scintigraphy with 99mTc-HMDP (hydroxymethylenediphosphonate), using a large-field computerized gamma camera with a parallel-hole collimator and SPECT. After performing early whole-body planar acquisitions at 5 minutes and late acquisitions at 3 hours after intravenous administration of approximately 700 MBq of Tc-99m HMDP, myocardial uptake was observed. Subsequently, targeted acquisitions and SPECT tomographic studies were performed on the myocardial uptake areas. All acquired images were subsequently subjected to quantitative and qualitative analysis, allowing us to extract a large number of parameters reflecting morphological and predictive characteristics using radiomics and more or less automated analysis algorithms. This analysis enabled us to obtain quantitative information that is not apparent in a qualitative image analysis. The ability to extract hidden information from digital medical images is of particular interest as it can enhance the predictive capabilities of existing automatic segmentation algorithms. Extracting new information that was previously hidden can be utilized for automatic image segmentation.

Chinese collaborative study of survival analysis in 980 patients with AL amyloidosis

AbstractBackgroundThe prognosis of patients with light‐chain amyloidosis (AL) has improved markedly in the past decade in China; whether the current staging systems are suitable to predict the overall survival (OS) of the patients remains undetermined.MethodsBased on 980 biopsy‐proved AL patients with 5‐year follow‐up from China Registration Network for Light‐chain Amyloidosis, we evaluated the efficacy of existing staging systems and developed a new stratification model. This involved analyzing parameters such as N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) thresholds and estimated glomerular filtration rate (eGFR).ResultsWe found that 30% patients were classified as stage I, 25% as stage II, 26% as stage III, and 19% as stage IV disease using the Mayo 2012 staging system, with varying median OS values. However, the observed median OS values were notably higher than previously reported. By incorporating NT‐proBNP thresholds and eGFR values, we developed a four‐stage score system. With this new model, 41.6% patients were reclassified to stage I, 34.3% to stage II, 17.8% to stage III, and 6.3% to stage IV disease, with adjusted median OS values.ConclusionThe new stratification model exhibited improved consistency compared to traditional staging systems. It effectively identified patients with the best and worst prognoses, even among those receiving comprehensive treatment. Specifically, NT‐proBNP levels exceeding 9000 pg/mL combined with an eGFR less than 60 mL/min/1.73 m2 proved superior in prognosticating patient outcomes. Overall, the median OS of AL amyloidosis patients in China has significantly improved, underscoring the need for tailored prognostic models in clinical practice.

A serious warning: A case report on localized amyloidosis of the oral cavity.

Amyloidosis is a relatively rare condition with an array of complex pathophysiology. Localized amyloidosis is a rare and benign condition that practically never results in any clinical repercussions in the head and neck area. Multiple soft nodules of the tongue, lip, and cheek are the most commonly described defining characteristics of localized oral amyloidosis. These nodules originate due to the proliferation of abnormally folded protein aggregates in the body's extracellular tissue compartments, which destroy organ structure and function. Herein, we address the case of a female infant aged one with a smooth nodule in the labial mucosa who was diagnosed with primary localized amyloidosis. When a patient is diagnosed with amyloidosis of the oral mucosa, the possibility of systemic amyloidosis or an underlying plasma cell dyscrasia must be ruled out. Surgical treatment may be beneficial for eliminating any functional impairment if primary localized amyloidosis is established.

Prognostic value of native T1 and extracellular volume in patients with immunoglubin light-chain amyloidosis

BackgroundCardiac involvement in patients with immunoglubin light-chain amyloidosis (AL) is a major determinant of treatment choice and prognosis, and early identification of high-risk patients can initiate intensive treatment strategies to achieve better survival. This study aimed to investigate the prognostic value of native T1 and ECV in patients with AL-cardiac amyloidosis (CA).MethodsA total of 38 patients (mean age 59 ± 11 years) with AL diagnosed histopathologically from July 2017 to October 2021 were collected consecutively. All patients were performed 3.0-T cardiac magnetic resonance (CMR) including cine, T1 mapping, and late gadolinium enhancement (LGE). Pre- and post-contrast T1 mapping images were transferred to a dedicated research software package (CVI42 v5.11.3) to create parametric T1 and ECV values. In addition, clinical and laboratory data of all patients were collected, and patients or their family members were regularly followed up by telephone every 3 months. The starting point of follow-up was the time of definitive pathological diagnosis, and the main endpoint was all-cause death. Kaplan-Meier analysis and Cox proportional risk model were used to evaluate the association between native T1 and ECV and death in patients with CA.ResultsAfter a median follow-up of 27 (16, 37) months, 12 patients with CA died. Kaplan-Meier analysis showed that elevated native T1 and ECV were closely associated with poor prognosis in patients with CA. The survival rate of patients with ECV > 44% and native T1 > 1389ms were significantly lower than that of patients with ECV ≤ 44% and native T1 ≤ 1389ms (Log-rank P < 0.001), and was not associated with the presence of LGE. After adjusting for clinical risk factors and CMR measurements in a stepwise multivariate Cox regression model, ECV [risk ratio (HR):1.37, 95%CI: 1.09–1.73, P = 0.008] and native T1 (HR:1.01, 95%CI: 1.00-1.02, P = 0.037) remained independent predictors of all-cause mortality in patients with CA.ConclusionsBoth native T1 and ECV were independently prognostic for mortality in patients with CA, and can be used as important indicators for clinical prognosis assessment of AL.

Complexities of Coexisting Cardiac Amyloidosis and Coronary Artery Disease: A Contemporary Review of Diagnostic and Treatment Approaches.

Cardiac amyloidosis (CA) represents an emerging challenge in cardiovascular medicine, with notable clinical overlaps and diagnostic complexities when coexisting with coronary artery disease (CAD). This integrative review navigates the intricate terrain of CA and CAD, elucidating epidemiology, clinical presentations, and diagnostic considerations. Examining both immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis, we underscore their shared demographic associations, diagnostic intricacies, and potential diagnostic confounders with CAD. Notably, we emphasize the impact of CA on epicardial coronary arteries and the consequential implications for coronary microcirculation. Further exploration reveals the connection between CA and acute myocardial infarction, emphasizing early recognition as pivotal. In terms of differential diagnosis, we underscore the significance of clinical symptoms, electrocardiography, echocardiography, cardiac magnetic resonance, and bone scintigraphy. Additionally, we scrutinize the intricate realm of treatment, encompassing medication selection, antithrombotic strategies, and revascularization modalities. Our review addresses the distinctive challenges posed by CA patients' limited tolerance for conventional therapies. This comprehensive synthesis serves as an invaluable resource for clinicians confronting the intricate intersection of CA and CAD. By offering insights into diagnostic refinement and innovative therapeutic avenues, we aim to enhance patient outcomes and quality of life within this complex clinical landscape.