A case of pleural and pericardium amyloidosis with effusion associated with multiple myeloma relapse.

An 80-year-old man with a history of Bence-Jones potein (BJP) λ-type multiple myeloma (MM), which had been in remission for 16 years, was examined for shortness of breath and was found to have bilateral pleural and pericardial effusions. A pleural fluid test and a pleural biopsy under local anaesthesia performed by a previous physician failed to make the diagnosis. Despite diuretic therapy, his condition necessitated frequent thoracentesis. The patient was referred to our hospital and thoracoscopic pleural and pericardial biopsies performed under general anaesthesia revealed λ-type AL amyloidosis, indicating a relapse of MM. Despite drug therapy for MM, the patient died from aspiration pneumonia. The case underscores the importance of considering amyloidosis in differential diagnoses for refractory effusions, especially in patients with a history of MM, even after long-term remission.

Recent advances in the diagnostic methods and therapeutic strategies of transthyretin cardiac amyloidosis.

Cardiac amyloidosis is a progressive disease characterized by the buildup of amyloid fibrils in the extracellular space of the heart. It is divided in 2 main types, immunoglobulin light chain amyloidosis and transthyretin amyloidosis (ATTR), and ATTR amyloidosis is further divided in 2 subtypes, non-hereditary wild type ATTR and hereditary mutant variant amyloidosis. Incidence and prevalence of ATTR cardiac amyloidosis is increasing over the last years due to the improvements in diagnostic methods. Survival rates are improving due to the development of novel therapeutic strategies. Tafamidis is the only disease-modifying approved therapy in ATTR amyloidosis so far. However, the most recent advances in medical therapies have added more options with the potential to become part of the therapeutic armamentarium of the disease. Agents including acoramidis, eplontersen, vutrisiran, patisiran and anti-monoclonal antibody NI006 are being investigated on cardiac function in large, multicenter controlled trials which are expected to be completed within the next 2-3 years, providing promising results in patients with ATTR cardiac amyloidosis. However, further and ongoing research is required in order to improve diagnostic methods that could provide an early diagnosis, as well as survival and quality of life of these patients.

Clinical characterization of patients with cardiac amyloidosis in a referral center of Colombia.

Objective: The objective of the study is to describe the characteristics of our first cohort of amyloidosis in a Latin America cardiovascular reference center in Colombia. Methods: This is a historic cohort study and data were taken from the electronic records of the Fundación Cardioinfantil-Instituto de cardiología; adult patients with a diagnosis of cardiac amyloidosis were included and a descriptive analysis was presented. Results: A total of 31 patients with amyloidosis were included. 17 were Transthyretin Amyloidosis (ATTR) subtype and 14 were AL subtype. An overall mortality of 25% was found. The mean age at diagnosis was 74 years, male sex predominant. More frequent comorbidities were hypertension and atrial fibrillation. The most frequent clinical presentation was congestive heart failure (75%), with mildly reduced ejection fraction (41.94%), followed by reduced ejection fraction (32.26%), and preserved ejection fraction (25.81%). In the ATTR subtype, a reduced ejection fraction was found at 41.18% and a mildly reduced ejection fraction at 35.29%. Conclusion: These results provide information on the most frequent type of amyloidosis and the late timing to diagnose in our historic cohort study, we present some of the baseline characteristics and most frequent approaches to diagnose Cardiac Amyloidosis that represents all challenges in clinical practice. Improvements are needed in the diagnosis and early treatment of these patients.

Objetivo: Describir las características de nuestra primera cohorte de amiloidosis en un centro de referencia cardiovascular de Latinoamérica en Colombia. Métodos: Los datos fueron tomados de los registros electrónicos de la Fundación Cardioinfantil- Instituto de cardiología; Se incluyeron pacientes adultos con diagnóstico de amiloidosis cardíaca y se presenta un análisis descriptivo. Resultados: Se incluyeron un total de 31 pacientes con amiloidosis. 17 eran ATTR y 14 eran AL. Se encontró una mortalidad global del 25%. La edad media al diagnóstico fue de 74 años, predominando el sexo masculino. Las comorbilidades más frecuentes fueron Hipertensión y Fibrilación auricular. La presentación clínica más frecuente fue insuficiencia cardíaca congestiva (75%), con fracción de eyección levemente reducida (41.94%), seguida de fracción de eyección reducida (32.26%) y fracción de eyección preservada (25.81%). En el subtipo ATTR, la fracción de eyección reducida se encontró en el 41.18% y la fracción de eyección levemente reducida en el 35.29%. Conclusión: Estos resultados brindan información sobre el tipo de amiloidosis más frecuente y el momento del diagnóstico, el cual fue tardío en nuestra cohorte, su prevalencia en el sexo masculino (61.29%), edad promedio al diagnóstico de 74 años, principal presentación clínica y abordaje más frecuente, mostrando el desafío que representa en la práctica clínica llegar al diagnóstico. Se necesitan mejoras en el diagnóstico y tratamiento precoz de estos pacientes.

Prevalence of transthyretin cardiac amyloidosis in patients with heart failure with preserved ejection fraction: the PRACTICA study.

INTRODUCTION AND OBJECTIVES: Transthyretin cardiac amyloidosis (ATTR-CA) is a frequent cause of heart failure with preserved ejection fraction (HFpEF). This study aimed to determine the prevalence of ATTR-CA in HFpEF patients in a multicenter nationwide study. METHODS: Consecutive ambulatory or hospitalized patients aged ≥ 50 years with HFpEF and left ventricle hypertrophy ≥ 12 mm were studied at 20 Spanish hospitals. Screening for CA was initiated according to the usual clinical practice at each center. Positive scintigraphs were analyzed centrally. RESULTS: A total of 422 patients were included, of whom 387 underwent further screening for CA. Sixty-five patients (16.8%) were diagnosed with ATTR-CA, and none was younger than 75 years. Prevalence increased with age. Among these patients, 60% were men, with a mean age of 85.3 ± 5.2 years, mean left ventricular ejection fraction of 60.3 ± 7.6%, and a mean maximum left ventricular wall thickness of 17.2 (range, 12-25) mm. Most of the patients were in New York Heart Association class II (48.4%) or III (46.8%). In addition to being older than patients without ATTR-CA, patients with ATTR-CA had higher median NT-proBNP levels (3801 [2266-7132] vs 2391 [1141-4796] pg/mL; P = .003). There was no statistically significant difference in the prevalence of ATTR-CA by sex (19.7% in men and 13.8% in women, P = .085). A genetic variant (ATTRv) was found in approximately 7% (4/56) of the patients. CONCLUSIONS: This multicenter nationwide study found that the prevalence of ATTR-CA was 16.8%, confirming it as a significant contributor to HFpEF in patients of both sexes with left ventricular hypertrophy older than 75 years.

Importance of fourth heart sound and preserved left atrial function in wild-type transthyretin amyloidosis.

AIMS: A fourth heart sound (S4) was reported to be almost never present in patients with amyloid light-chain cardiomyopathy. There have been no reports on S4 in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). This study aimed to clarify the clinical implications of S4 in patients with ATTRwt-CM. METHODS AND RESULTS: Seventy-six patients with ATTRwt-CM (mean age: 80.4 ± 5.4 years, 68 males) who had undergone phonocardiography (PCG) were retrospectively assessed. We measured S4 amplitude on digitally recorded PCG. S4 was considered to be present when its amplitude was 1.0 mm or greater on the PCG. Distinct S4 was defined as S4 with an amplitude of 2.0 mm or greater, which is usually recognizable by auscultation. According to the rhythm and presence or absence of S4, the patients were divided into three groups, namely, sinus rhythm (SR) with S4, SR without S4, and non-SR. Non-SR consisted of atrial fibrillation, atrial flutter, and atrial tachycardia. Thirty-six patients were in SR and the remaining 40 patients were in non-SR. In the 36 patients in SR, S4 was shown by PCG to be present in 17 patients (47%), and distinct S4 was recognized in 7 patients (19%) by auscultation. In patients who were in SR, those with S4 had higher systolic blood pressure (124 ± 15 vs. 99 ± 8 mmHg, P < 0.001), lower level of plasma B-type natriuretic peptide (308 [interquartile range (IQR): 165, 354] vs. 508 [389, 765] pg/mL, P = 0.034) and lower level of high-sensitivity cardiac troponin T (0.068 [0.046, 0.089] vs. 0.109 [0.063, 0.148] ng/mL, P = 0.042) than those without S4. There was no significant difference in left atrium (LA) volume index or LA reservoir strain between patients with S4 and without S4. Patients with S4 had more preserved LA systolic function than those without S4 (peak atrial filling velocity: 53 ± 25 vs. 34 ± 9 cm/s, P = 0.033; LA contractile strain: 4.1 ± 2.1 vs. 1.6 ± 2.0%, P = 0.012). Patients in SR without S4 had worse short-term prognosis compared with the other two groups (generalized Wilcoxon test, P = 0.033). CONCLUSIONS: S4 was present in 47% of the patients in SR with ATTRwt-CM. Patients in SR without S4 had more impaired LA systolic function than those in SR with S4. The absence of S4 portends a poor short-term prognosis in patients with ATTRwt-CM.

Cardiac Amyloidosis: A Comprehensive Review of Pathophysiology, Diagnostic Approach, Applications of Artificial Intelligence, and Management Strategies.

Cardiac amyloidosis (CA) is a serious and often fatal condition caused by the accumulation of amyloid fibrils in the heart, leading to progressive heart failure. It involves the misfolding of normally soluble proteins into insoluble amyloid fibrils, with transthyretin and light-chain amyloidosis being the most common forms affecting the heart. Advances in diagnostics, especially cardiac magnetic resonance imaging and non-invasive techniques, have improved early detection and disease management. Artificial intelligence has emerged as a diagnostic tool for cardiac amyloidosis, improving accuracy and enabling earlier intervention through advanced imaging analysis and pattern recognition. Management strategies include volume control, specific pharmacotherapies like tafamidis, and addressing arrhythmias and advanced heart failure. However, further research is needed for novel therapeutic approaches, the long-term effectiveness of emerging treatments, and the optimization of artificial intelligence applications in clinical practice for better patient outcomes. The article aims to provide an overview of CA, outlining its pathophysiology, diagnostic advancements, the role of artificial intelligence, management strategies, and the need for further research.

Connective tissue amyloidosis in patients referred for orthopedic surgery. CONNECT-AMY study. / Amiloidosis del tejido conectivo en pacientes referidos a cirugía ortopédica. Estudio CONNECT-AMY.

INTRODUCTION AND OBJECTIVE: Clinical manifestations secondary to amyloid deposition in connective tissue may allow early detection of amyloidosis. We sought to identify the prevalence of connective tissue amyloidosis in patients undergoing orthopedic surgery and evaluate for cardiac involvement. MATERIAL AND METHODS: Descriptive cross-sectional study that included patients >50 years referred for orthopedic surgery at our center. A sample of the affected connective tissue was taken during the intervention to evaluate the presence of amyloid material. Those with confirmed amyloidosis were further evaluated with complementary tests for cardiac involvement. RESULTS: Forty-eight patients were included. Mean age was 65.4 years and 41.7% were women. The most frequent surgery was supraspinatus tendon rupture (50%). Transthyretin amyloid deposits were detected in 2 patients (4.2%). The absence of variants in the protein gene established the diagnosis of ATTRwt in both cases. None of them presented cardiac involvement. CONCLUSIONS: In this study, 4.2% of patients referred for orthopedic surgery presented transthyretin amyloidosis in the affected connective tissue.

Long-Term Rehabilitation Therapy Is Effective for Physical Function in a Patient With Amyloid Light Chain Amyloidosis Complicated by Nephrotic Syndrome: A Case Report and Literature Review.

We report on the rehabilitation of a patient with amyloid light chain (AL) amyloidosis complicated by nephrotic syndrome. Various symptoms produced by AL amyloidosis, including nephrotic syndrome, complicate rehabilitation therapy. In this case report, long-term physical therapy was initiated prior to autologous peripheral blood stem cell transplantation owing to the risk of further decline in physical function due to decreased mobility and physical activity. Patients were instructed on how to perform home exercise therapy. Furthermore, compliance was monitored using a checklist and regular face-to-face feedback. There was no increase in skeletal muscle mass, but improvements in grip strength, lower extremity muscle strength, and phase angle were observed after 24 weeks of physical therapy. Despite the absence of partial remission (urinary protein level of 3.5 g/gCre or higher), nephrotic syndrome demonstrated a trend toward improvement. Since the effectiveness of physical therapy in such patients has not yet been fully established, this report suggests that long-term rehabilitation therapy for physical function in patients with nephrotic syndrome complicated by persistent proteinuria may be effective.

Intracerebral inoculation of healthy non-transgenic rats with a single aliquot of oligomeric amyloid-ß (1-42) profoundly and progressively alters brain function throughout life.

One of the puzzling aspects of sporadic Alzheimer's disease (AD) is how it commences. Changes in one key brain peptide, amyloid-beta (Aß), accompany disease progression, but whether this comprises a trigger or a consequence of AD is still a topic of debate. It is clear however that the cerebral presence of oligomeric Aß (1-42) is a key factor in early AD-pathogenesis. Furthermore, treatment of rodent brains with oligomeric Aß (1-42) either in vitro or in vivo, acutely impairs hippocampal synaptic plasticity, creating a link between Aß-pathology and learning impairments. Here, we show that a once-off inoculation of the brains of healthy adult rats with oligomeric Aß (1-42) exerts debilitating effects on the long-term viability of the hippocampus, one of the primary targets of AD. Changes are progressive: months after treatment, synaptic plasticity, neuronal firing and spatial learning are impaired and expression of plasticity-related proteins are changed, in the absence of amyloid plaques. Early changes relate to activation of microglia, whereas later changes are associated with a reconstruction of astroglial morphology. These data suggest that a disruption of Aß homeostasis may suffice to trigger an irreversible cascade, underlying progressive loss of hippocampal function, that parallels the early stages of AD.

Renal Amyloidosis in a Child with Recessive Dystrophic Epidermolysis Bullosa Due to a Novel Variant in COL7A1 Gene.

Secondary amyloidosis may complicate inherited dermatoses, but recessive dystrophic epidermolysis bullosa (RDEB) complicated by renal amyloidosis is rare. We report a case of a 12-year-old male child with RDEB presenting with progressive generalized anasarca for 20 days. Kidney biopsy showed diffuse expansion of mesangial matrix by pale acellular Periodic Acid-Schiff (PAS)-negative amorphous material, which was congophilic on Congo red stain and gave apple green birefringence on polarization and extending along the glomerular basement membrane, suggestive of amyloidosis. Genetic analysis showed a compound heterozygous pathogenic variant in the COL7A1 gene with autosomal recessive inheritance.

Experience with tafamidis in peritoneal dialysis for a patient diagnosed with transthyretin cardiac amyloidosis.

Cardiac amyloidosis is a cardiomyopathy resulting from the extracellular deposition of proteins such as transthyretin (TTR). We present the case of a 72-year-old male with hereditary cardiac amyloidosis. After confirming the diagnosis, tafamidis, a TTR stabilizer, was administered. Remarkably, tafamidis, when coupled with peritoneal dialysis for chronic kidney disease, maintained stability in both cardiac and renal functions. Previous studies have demonstrated the efficacy of tafamidis in reducing all-cause mortality and cardiovascular hospitalizations, although its use in severe renal failure lacks specific evaluation. This case suggests a potential application of tafamidis in moderate-severe kidney disease, emphasizing the need for further research in this population.

Anomalous Coronary Artery Identified Post Heart Transplantation.

The following case details a 67-year-old male with a history of heart failure with reduced ejection fraction secondary to cardiac amyloidosis who underwent orthotopic heart transplantation and was later found to have an anomalous left circumflex arising from the right coronary artery in the donor heart.

HOVON 104, long-term follow-up of bortezomib-dexamethasone induction therapy followed by autologous stem cell transplantation in newly diagnosed AL amyloidosis patients.

The HOVON 104 studied bortezomib-dexamethasone induction therapy and autologous stem cell transplantation in 50 patients, of whom 35 received an autologous stem cell transplantation (ASCT). We demonstrate a 5-year overall survival (OS) of 73% and progression-free survival (PFS) of 52% for all 50 patients with a median follow-up of 61.3 months. For the 35 transplanted patients, calculated from the date of ASCT, the 5-year OS and PFS were 91% and 68%, respectively. After ASCT, the rate of organ response improved over time but stabilized around 3 years. A complete cardiac response was seen in around 60% of patients and remained stable from 2 years onward. Reaching complete renal response was slower over time and achieved by 61% of the renal-affected patients at 5 years. We confirm the excellent outcomes after ASCT and demonstrate a 60% complete organ response with longer follow-up.

Cardiac amyloidosis red flags: What all the cardiologist have to know.

Cardiac amyloidosis is becoming increasingly important among cardiologist and an early diagnosis is very important. Amyloidosis is a systemic disease and many cardiac and extracardiac elements (red flags) should raise the suspicion of the disease. Electrocardiographic and imaging techniques (such as echocardiography, cardiac magnetic resonance and scintigraphy) are useful tools to make a diagnosis together with the presence of orthopedic issues, peripheral neuropathy or plasma cell dyscrasia. Cardiac amyloidosis is also often associated with valvular disorder, heart failure or cardiomyopathy. Red flags are crucial to raise suspicion and reach an early diagnosis, in order to start a targeted treatment strategy that could change the patient's outcome. Indeed, in the last years four new drugs were approved to treat transthyretin amyloidosis.

Dermoscopy of Amyloidosis Cutis Dyschromica.

Amyloidosis cutis dyschromica is a very rare form of primary cutaneous amyloidosis characterized by prepubertal onset of hyper and hypopigmented spots and amyloid deposits in the papillary dermis. We report two cases of this condition highlighting its dermoscopic findings.

Localized AL amyloidosis of the breast in a geriatric female.

Localized breast amyloidosis is often found incidentally on mammography or ultrasound, as amyloid deposits can be calcified and mimic malignancy. Although rare, breast amyloidosis should be considered a possible etiology of abnormal mammography findings in older women.

Emerging multisystem biomarkers in hereditary transthyretin amyloidosis: a pilot study.

Hereditary transthyretin (ATTRv) amyloidosis is a rare, adult-onset, progressive, multisystemic condition caused by TTR pathogenic variants. Reliable biomarkers are needed to allow early diagnosis and to monitor disease severity and progression. We measured serum concentrations of growth differentiation factor-15 (GDF-15) and uromodulin (Umod) in ATTRv patients to evaluate correlations with standard markers of disease severity (FAP stage and PND score). Blood samples were collected from 16 patients diagnosed with ATTRv amyloidosis and a verified TTR variant and from 26 healthy controls. ATTRv patients were stratified by clinical phenotype (neurologic vs. mixed), genotype (V30M vs. non-V30M), and disease severity. We found significantly higher levels of serum GDF-15 in ATTRv patients compared with controls. Mean serum Umod levels were significantly lower in patients with ATTRv than controls. A positive correlation was found between serum Umod and estimated glomerular filtration rate (eGFR), while an inverse correlation was found with cystatin C levels. Conversely, GDF-15 showed a negative correlation with eGFR, and a direct correlation with cystatin C levels. No correlation was demonstrated between GDF-15 or Umod levels and traditional cardiac biomarkers. The results identify alteration of serum levels of GDF-15 and Umod in ATTRv amyloidosis.