Catheter ablation of atrial arrhythmias in cardiac amyloidosis: Impact on heart failure and mortality.

BACKGROUND: Atrial arrhythmias (AA) commonly affect patients with cardiac amyloidosis (CA) and are a contributing risk factor for the development of heart failure (HF). This study sought to investigate the long-term efficacy and impact of catheter ablation on HF progression in patients with CA and AA. METHODS: Thirty-one patients with CA and AA undergoing catheter ablation were retrospectively included (transthyretin-ATTR CA 61% and light chain-AL CA 39%). AA subtypes included atrial fibrillation (AFib) in 22 (paroxysmal in 10 and persistent in 12), atrial flutter (AFl) in 17 and atrial tachycardia (AT) in 11 patients. Long-term AA recurrence rates were evaluated along with the impact of sinus rhythm (SR) maintenance on HF and mortality. RESULTS: AA recurrence was observed in 14 patients (45%) at a median of 3.5 months (AFib n = 8, AT n = 6, AFl = 0). Post-cardioversion, medical therapy or catheter ablation, 10 patients (32%) remained in permanent AA. Over a median follow-up of 19 months, all-cause mortality was 39% (n = 12): 3 with end-stage HF, 5 due to late complications of CA, 1 sudden cardiac death, 1 stroke, 1 COVID 19 (and one unknown). With maintenance of SR following catheter ablation, significant reductions in serum creatinine and natriuretic peptide levels were observed with improvements in NYHA class. Two patients required hospitalization for HF in the SR maintenance cohort compared to 5 patients in the AA recurrence cohort (p = 0.1). All 3 patients with deaths secondary to HF had AA recurrence compared to 11 out of the 28 patients whom were long-term survivors or deaths not related to HF (p = 0.04). All-cause mortality was not associated with AA recurrence. CONCLUSION: This study demonstrates moderate long-term efficacy of SR maintenance with catheter ablation for AA in patients with CA. Improvements in clinical and biological status with positive trends in HF mortality are observed if SR can be maintained.

Novel monoclonal antibodies: A really specific therapy for light chain amyloidosis.

Light chain amyloidosis is a rare disease caused by clonal plasma cells in the bone marrow generating an excessive amount of immunoglobulin light chains. These chains misfold and produce insoluble fibrils that deposit in various organs, including the heart, kidneys, liver, nervous system, and digestive tract. Life expectancy and symptoms during the course of the disease vary depending on which and how many organs are affected. Targeted plasma cell therapy has significantly advanced the clinical management of amyloidosis, with ongoing progress. However, current clinical studies are investigating innovative targets, drug combinations and treatment strategies to improve therapeutic outcomes by minimizing adverse effects and refining patient prognosis in these challenging hematological conditions. In this paper, we review the state of the art regarding the use of anti-amyloid antibodies, as a revolutionary and innovative approach in the current scenario of amyloid treatment.

Bilateral Hilar and Mediastinal Lymphadenopathy as an Initial Manifestation of Amyloidosis.

A 75-year-old male visited our hospital with bilateral hilar lymph node swelling detected on chest radiography during an annual medical checkup. Chest computed tomography revealed swelling of multiple hilar mediastinal lymph nodes. Histopathological and immunohistochemical examinations of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimens from the hilar lymph nodes revealed amyloid deposition. Bilateral hilar and mediastinal lymphadenopathies can be the first manifestations of amyloidosis diagnosed using EBUS-TBNA.

Cardiac Amyloidosis Due to Transthyretin Protein: A Review.

Importance: Systemic amyloidosis from transthyretin (ATTR) protein is the most common type of amyloidosis that causes cardiomyopathy. Observations: Transthyretin (TTR) protein transports thyroxine (thyroid hormone) and retinol (vitamin A) and is synthesized predominantly by the liver. When the TTR protein misfolds, it can form amyloid fibrils that deposit in the heart causing heart failure, heart conduction block, or arrhythmia such as atrial fibrillation. The biological processes by which amyloid fibrils form are incompletely understood but are associated with aging and, in some patients, affected by inherited variants in the TTR genetic sequence. ATTR amyloidosis results from misfolded TTR protein deposition. ATTR can occur in association with normal TTR genetic sequence (wild-type ATTR) or with abnormal TTR genetic sequence (variant ATTR). Wild-type ATTR primarily manifests as cardiomyopathy while ATTR due to a genetic variant manifests as cardiomyopathy and/or polyneuropathy. Approximately 50 000 to 150 000 people in the US have heart failure due to ATTR amyloidosis. Without treatment, heart failure due to ATTR amyloidosis is associated with a median survival of approximately 5 years. More than 130 different inherited genetic variants in TTR exist. The most common genetic variant is Val122Ile (pV142I), an allele with an origin in West African countries, that is present in 3.4% of African American individuals in the US or approximately 1.5 million persons. The diagnosis can be made using serum free light chain assay and immunofixation electrophoresis to exclude light chain amyloidosis combined with cardiac nuclear scintigraphy to detect radiotracer uptake in a pattern consistent with amyloidosis. Loop diuretics, such as furosemide, torsemide, and bumetanide, are the primary treatment for fluid overload and symptomatic relief of patients with ATTR heart failure. An ATTR-directed therapy that inhibited misfolding of the TTR protein (tafamidis, a protein stabilizer), compared with placebo, reduced mortality from 42.9% to 29.5%, reduced hospitalizations from 0.7/year to 0.48/year, and was most effective when administered early in disease course. Conclusions and Relevance: ATTR amyloidosis causes cardiomyopathy in up to approximately 150 000 people in the US and tafamidis is the only currently approved therapy. Tafamidis slowed progression of ATTR amyloidosis and improved survival and prevented hospitalization, compared with placebo, in people with ATTR-associated cardiomyopathy.

Gastroduodenal Involvement in AL Amyloidosis: Case Report and Literature Review.

Gastrointestinal amyloidosis is a rare condition commonly found in the setting of systemic AL amyloidosis. Amyloid can deposit throughout the gastrointestinal tract and the resulting symptoms vary depending on the site of deposition. Gastrointestinal (GI) manifestations can range from weight loss or abdominal pain, to more serious complications like gastrointestinal bleeding, malabsorption, dysmotility, and obstruction. This case describes a patient with known history of IgG lambda AL amyloidosis, presenting with epigastric pain and unintentional weight loss found to have gastroduodenal amyloidosis. The definitive diagnosis of GI amyloidosis requires endoscopic biopsy with Congo red staining and visualization under polarized light microscopy. There are currently no specific guidelines for the management of GI amyloidosis. Generally, the goal is to treat the underlying cause of the amyloidosis along with symptom management. Our patient is being treated with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) and started on hemodialysis due to progression of renal disease.

Being a Better Starfish Thrower, Carpal Tunnel Syndrome, and Cardiac Amyloidosis: The Hand Surgeon's Opportunity to Make a Profound Difference.

In recent years, there is increasing literature in cardiac and hand surgery journals demonstrating a stronger association between seemingly idiopathic carpal tunnel and amyloidosis. Despite this, it can be difficult for hand surgeons to identify who need biopsies, and this is further complicated by the cost of a biopsy and the low likelihood that a patient has cardiac amyloidosis. In patients with cardiac amyloidosis and carpal tunnel syndrome (CTS), CTS is typically diagnosed 5-10 years prior. Early diagnosis of cardiac amyloidosis is crucial, as current medications work to slow disease progression, but do not treat existing amyloid deposits. Hand surgeons can play an essential role in early diagnosis. The patient case discussed describes a man who had a carpal tunnel biopsy because of his bilateral CTS, recurrent trigger fingers, and his age. After confirmation of amyloidosis, he was referred for cardiac amyloidosis evaluation. Testing confirmed this diagnosis, and he was started on tafamidis, which studies show provide patients an opportunity for increased survival and quality of life. The responsibility falls on cardiologists and hand surgeons to continue refining the indications for carpal tunnel biopsy and spreading awareness of carpal tunnel biopsy and amyloid testing, as much work is still needed.

Cardiac MRI feature-tracking-derived torsion mechanics in systolic and diastolic dysfunction in systemic light-chain cardiac amyloidosis.

AIM: To describe the myocardial torsion mechanics in cardiac amyloidosis (CA), and evaluate the correlations between left ventricle (LV) torsion mechanics and conventional parameters using cardiac magnetic resonance imaging feature tracking (CMR-FT). MATERIALS AND METHODS: One hundred and thirty-nine patients with light-chain CA (AL-CA) were divided into three groups: group 1 with preserved systolic function (LV ejection fraction [LVEF] ≥50%, n=55), group 2 with mildly reduced systolic function (40% ≤ LVEF <50%, n=51), and group 3 with reduced systolic function (LVEF <40%, n=33), and compared with age- and gender-matched healthy controls (n=26). All patients underwent cine imaging and late gadolinium-enhancement (LGE). Cine images were analysed offline using CMR-FT to estimate torsion parameters. RESULTS: Global torsion, base-mid torsion, and peak diastolic torsion rate (diasTR) were significantly impaired in patients with preserved systolic function (p<0.05 for all), whereas mid-apex torsion and peak systolic torsion rate (sysTR) were preserved (p>0.05 for both) compared with healthy controls. In patients with mildly reduced systolic function, global torsion and base-mid torsion were lower compared to those with preserved systolic function (p<0.05 for both), while mid-apex torsion, sysTR, and diasTR were preserved (p>0.05 for all). In patients with reduced systolic function, only sysTR was significantly worse compared with mildly reduced systolic function (p<0.05). At multivariable analysis, right ventricle (RV) end-systolic volume RVESV index and NYHA class were independently related to global torsion, whereas LVEF was independently related to sysTR. RV ejection fraction (RVEF) was independently related to diasTR. LV global torsion performed well (AUC 0.71; 95% confidence interval [CI]: 0.61, 0.77) in discriminating transmural from non-transmural LGE in AL-CA patients. CONCLUSION: LV torsion mechanics derived by CMR-FT could help to monitor LV systolic and diastolic function in AL-CA patients and function as a new imaging marker for LV dysfunction and LGE transmurality.

Rare vertebral pathological fracture in primary amyloidosis.

Spinal involvement in primary amyloidosis is an exceedingly rare condition, presenting with typical pathological fracture symptoms that are often indistinguishable from other pathologies such as bone metastasis, metabolic disorders and infections. Histopathological studies for tissue diagnosis are the cornerstone of a definitive diagnosis, leading to successful treatment. Early diagnosis and intervention play a pivotal role in the care of patients with amyloidosis. Here, we present a unique case of a pathological fracture in the L4 vertebra following minor trauma. This fracture manifested with pain, instability and limitations in daily activities in a patient who had already been diagnosed with systemic amyloidosis and was undergoing chemotherapy. This case represents a distinct instance of vertebral involvement in amyloidosis and was managed with both chemotherapy and surgical intervention to address the spinal pathology, resulting in favourable outcomes.

A case of intestinal intussusception with unique hemorrhagic polyps due to AL amyloidosis and excessive anticoagulation.

Most adult intussusceptions are secondary to various pathological conditions that serve as a lead point. Because of their serious nature, intussusceptions often require emergency surgery. We report a surgical case of amyloidosis associated with intussusception, probably due to polypoid protrusions and bleeding tendencies. An 80-year-old man with abdominal pain was suspected of having jejunal intussusception on computed tomography. He had been prescribed warfarin for atrial fibrillation, and excessive anticoagulation was observed with a prolonged prothrombin time/international normalized ratio of 5.44 at presentation. After the excessive anticoagulation was resolved, emergency surgery was performed. The intussuscepted jejunum was resected, and a 7 cm long dark-red pedunculated polyp was identified as the lead point, which was accompanied by multiple small pedunculated polyps. Histopathological examination showed that these were all hemorrhagic polyps. Amyloid depositions were observed in the muscularis mucosae, submucosa, and the walls of the blood vessels. Immunohistochemical analysis revealed immunoglobulin light chain amyloidosis. This case is informative to discuss the clinical sequelae of gastrointestinal amyloid deposition.

Efficacy of topical gabapentin in women with primary macular amyloidosis: A side-by-side triple-blinded randomized clinical trial.

BACKGROUND: Primary cutaneous macular amyloidosis (PCMA) is a chronic pruritic cutaneous disease characterized by heterogeneous extracellular deposition of amyloid protein in the skin. AIMS: This study aimed to evaluate the efficacy of topical 6% gabapentin cream for the treatment of patients with PCMA. MATERIALS AND METHODS: In this triple-blind clinical trial, a total of 34 patients, who were diagnosed with PCMA, treated using two different strategies of topical gabapentin as the active group and vehicle cream as the control group. RESULTS: Pruritus score reduction in both groups was statistically significant compared with the baseline value (p < 0.001). There was a significant pigmentation score reduction in intervention group compared with control group after 1 month of the study (p < 0.001). The differences of pigmentation score changes between the groups were not significant at month 2 (p = 0.52) and month 3 (p = 0.22). CONCLUSIONS: The results of this study suggest that topical gabapentin cream may be effective as a topical agent in the treatment of pruritus associated with PCMA without any significant adverse effects. It is recommended to perform similar studies with a larger sample size and longer duration in both sexes.

[A Case of Transverse Colon Cancer with Gastrointestinal Amyloidosis Prevented from Anastomotic Leakage by Multidimensional Approach].

The patient was a 68-year-old woman who was on hemodialysis due to systemic amyloidosis and nephrotic syndrome. Biopsy revealed amyloid deposition in the stomach, duodenum, and colon. A transverse colon tumor was found on a follow- up CT after the aortic dissection surgery. We performed lower gastrointestinal endoscopy and contrast-enhanced CT and diagnosed transverse colon cancer with gastric wall infiltration(cStage Ⅲc). We considered that transverse colon resection was oncologically sufficient. However, due to concurrent gastrointestinal amyloidosis, which increased the risk of anastomotic leakage we performed laparoscopic extended right hemicolectomy to avoid colon-colon anastomosis with partial gastrectomy. Additionally intraoperative indocyanine green(ICG)fluorescence imaging showed that the fluorescence signal in the small intestinal wall was satisfactory, while it was weak in the colon wall. As a result, we suspected of impaired blood flow of colon wall due to an amyloidosis, so we additionally created a loop ileostomy. It is said that gastrointestinal amyloidosis raises the risk of anastomotic leakage. A case of transverse colon cancer complicated by gastrointestinal amyloidosis in which we successfully prevented anastomotic leakage through a multidimensional evaluation and approach is reported, along with a literature review.

Unraveling the genome: Familial Mediterranean fever.

ABSTRACT: Familial Mediterranean fever (FMF) is an inherited, autoinflammatory disease with a high prevalence in Middle Eastern and Mediterranean populations including Turks, Iranian, Spanish, Sephardic Jews, Arabs, and other Mediterranean ethnic groups. Autoinflammatory diseases are genetically predetermined disorders with multisystem effects primarily caused by defects in innate immunity. Although primarily known for an autosomal recessive mode of inheritance, there are increasing case reports associated with single Mediterranean fever (MEFV) mutation or dominant transmission. There have been over 300 variants identified in the MEFV gene; however, roughly 9-11 variants are responsible for the phenotypical expression seen with FMF. Symptoms include recurrent episodes of fever of unknown origin, abdominal, chest, or joint pain because of serosal inflammation. Persistent elevations in serum amyloid A can lead to complications like renal amyloidosis, kidney dysfunction, and end-stage kidney disease. Familial Mediterranean fever is diagnosed clinically using the Tel-Hashomer criteria and confirmed through genetic testing. Treatment includes initiation of colchicine with the goal of stopping attacks and preventing renal dysfunction and end-stage kidney disease. Genetic testing helps to identify the specific mutation allowing the provider to create a patient-specific treatment plan, monitor for complications such as renal amyloidosis, and enhance knowledge on the genetic heterogeneity and possible epigenetic factors.

Adult patient diagnosed with Muckle-Wells syndrome, antiphospholipid syndrome and glomerular haematuria.

Muckle-Wells syndrome (MWS) is a genetic periodic fever syndrome characterised by urticaria, fever and malaise starting in childhood with the development of perceptive hearing loss and risk of amyloidosis later in life.Patient A, in his 60s, was referred to a nephrologist because of glomerular haematuria and elevated erythrocyte sedimentation rate. He appeared to have periodic fevers since childhood, skin changes in cold circumstances and progressive deafness since he was 30 years of age. Genetic analysis revealed a pathogenic variant in the NLRP3 gene compatible with MWS. Treatment with anakinra (interleukin 1 antagonist) improved his symptoms, but only mild episodic arthralgia remained. Glomerular erythrocyturia diminished during treatment, supposing a relation between MWS and haematuria.This case report shows that rare genetic fever syndromes starting from early childhood can still be diagnosed in adult patients, with important therapeutic consequences. Symptoms can be relieved and amyloidosis with potential renal failure may be prevented.

An interesting case of AL amyloidosis and MM: a complex scenario with cardiac involvement.

Our patient presented with complaints of progressive shortness of breath for 1 month. She was diagnosed with a case of infiltrative type of restrictive cardiomyopathy (RCM) based on echocardiography and cardiac MRI findings. Her fat pad biopsy was suggestive of AL type of amyloidosis (AL). She was diagnosed with a case of multiple myeloma (MM) based on bone marrow biopsy findings with 48% plasma cells and a skeletal survey with lytic bone lesions on the skull, thus meeting the Crab criteria. We want to highlight the complex nature of this case and the difficulties associated with making a diagnosis. This case report presents an excellent opportunity to touch on the interesting topics of RCM, amyloidosis and MM.

A case of bilateral amyloidosis localized to extraocular muscles mimicking thyroid eye disease.

BACKGROUND: Amyloidosis is a rare condition characterized by the abnormal deposition of amyloid proteins in various tissues and organs. While systemic amyloidosis has been well-documented, amyloid deposition in extraocular muscles is an exceptionally rare occurrence, with only 35 reported cases. This case report sheds light on the importance of considering amyloidosis in the differential diagnosis of patients presenting with proptosis and diplopia, which are often associated with thyroid eye disease. CASE PRESENTATION: A woman in her twenties sought medical attention due to a complaint of diplopia. Her ocular examination revealed almost normal findings except for exotropia and proptosis. Orbital magnetic resonance imaging displayed fusiform enlargement of nearly all eye muscles, a presentation typically observed in thyroid eye disease. However, despite corticosteroid therapy, her symptoms showed no improvement. Given the unusual lack of response to conventional treatment, and inhomogeneous enhancement of the muscle, an extraocular muscle biopsy was conducted. This biopsy yielded a unique finding-amyloid deposition within the muscle tissue. This discovery was particularly intriguing due to the extreme rarity of amyloidosis affecting extraocular muscles, with fewer than three dozen documented cases worldwide. CONCLUSION: This unique case underscores the critical need for a comprehensive approach to diagnosing patients with proptosis and diplopia. While these symptoms are commonly attributed to thyroid eye disease, it is essential to consider alternative diagnoses such as amyloidosis, especially when standard treatments fail to yield results. The discovery of amyloid deposition in the extraocular muscles, although exceedingly rare, emphasizes the significance of a thorough differential diagnosis. In conclusion, this case report highlights the importance of vigilance in clinical practice, encouraging ophthalmologists to explore less common diagnostic possibilities when faced with challenging cases. Further research and clinical investigation are warranted to better understand the mechanisms and potential treatments for amyloidosis affecting the extraocular muscles.

Albuminuria in transthyretin cardiac amyloidosis: Prevalence, progression and prognostic importance.

AIMS: Transthyretin cardiac amyloidosis (ATTR-CA) is an infiltrative cardiomyopathy that commonly presents with concomitant chronic kidney disease. Albuminuria is common in heart failure and associated with worse outcomes, but its prevalence and relationship to outcome in ATTR-CA remains unclear. METHODS AND RESULTS: A total of 1181 patients with ATTR-CA were studied (mean age 78.1 ± 7.9 years; 1022 [86.5%] male; median estimated glomerular filtration rate 59 ml/min/1.73m2 [interquartile range: 47-74]). Albuminuria was present in 563 (47.7%) patients (499 [88.6%] with microalbuminuria and 64 [11.4%] with macroalbuminuria). Patients with albuminuria had a more severe cardiac phenotype evidenced by higher serum cardiac biomarkers (median N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 4027 ng/L [2173-6889] vs. 1851 ng/L [997-3209], p < 0.001; median troponin T: 69 ng/L [46-101] vs. 48 ng/L [34-68], p < 0.001) and worse echocardiographic indices of systolic (longitudinal strain: -10.0 ± 3.6% vs. -11.6 ± 3.8%, p < 0.001) and diastolic function (E/e': 17.5 ± 6.4 vs. 16.4 ± 6.7, p < 0.001) than those with a normal urinary albumin to creatinine ratio (UACR). Microalbuminuria and macroalbuminuria were independently associated with mortality in the overall population (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.13-1.92, p = 0.005 and HR 1.87, 95% CI 1.15-3.05, p = 0.012, respectively). In a subgroup of patients (n = 349) without concomitant hypertension, diabetes mellitus or chronic kidney disease, albuminuria was also associated with mortality (HR 2.98, 95% CI 1.72-5.17, p < 0.001). At 12 months, 330 patients had a repeat UACR measurement; those in whom UACR increased by 30% or more (n = 148, 44.8%) had an increased risk of mortality (HR 1.84, 95% CI 1.06-3.19, p = 0.030). CONCLUSIONS: Albuminuria is common in patients with ATTR-CA, and more prevalent in those with a more severe cardiac phenotype. Albuminuria at diagnosis and a significant increase in UACR during follow-up are associated with mortality.