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Medscape
10 hours ago
- Health
- Medscape
Fast Five Quiz: ATTR-CM Presentation and Diagnosis
Transthyretin amyloid cardiomyopathy (ATTR-CM) presents with a diverse range of symptoms involving the cardiovascular and peripheral systems. The clinical manifestations of ATR-CM are typically related to the location of amyloid fibrils in various tissues. In individuals with hereditary transthyretin amyloid, the type of TTR mutation also influences the presentation. Owing to the heterogeneity of presentation, diagnosis might be delayed for several years after symptom onset. In addition, the true prevalence of the disease is unknown because many cases go undiagnosed and patients are also often misdiagnosed with more common conditions. Are you up to date on your understanding of ATTR-CM presentation and diagnosis? Test your knowledge with a quick quiz. ATTR-CM can affect several organ systems outside of the heart and periphery, disrupting gastrointestinal, genitourinary, auditory, and vision functions. Ocular manifestations (usually caused by vitreous deposits) include conjunctivitis, dry eye, floaters, reduced visual acuity, and eye pain. Regarding other extracardiac manifestations, neuropathic pain, a consequence of deposits in the peripheral nerves, can result in weakness and impaired sensation, as well as autonomic dysfunction that manifests as sexual or urinary dysfunction. Cardiac manifestations of ATTR-CM can include symptoms associated with chronic heart failure, such as dyspnea on exertion and peripheral edema, and arrythmias (such as syncope). Learn more about the clinical presentation of ATTR-CM. Echocardiography can reveal signs of amyloid deposition within the heart. Characteristic imaging findings can include increased ventricular wall thickness, increased septal thickness, valvular thickening, valvular insufficiency, and atrial enlargement. The myocardium might also appear to have a granular "sparkling" appearance, as indicated by bright spots in the image. Although this sign alone is not sufficient to confirm a diagnosis, it is suggestive of ATTR-CM and can help with diagnosis. Thinning of the valvular walls and reduced septal thickness are usually not indicative of cardiac amyloid deposition. Though increased diastolic volume might be seen in patients with cardiac amyloid deposition, this factor alone is not definitive. Specifically, a common presentation of cardiac amyloidosis is ' rapidly progressive diastolic dysfunction in a nondilated ventricle.' Learn more about cardiac imaging in AT TR-CM. Patients who exhibit possible signs of cardiac amyloidosis should be screened using electrophysiology and imaging to detect any abnormalities due to amyloid deposits. If those results are suggestive of cardiac amyloidosis, additional tests must be ordered to determine the amyloidosis type. The first step in the differential diagnostic pathway includes testing for the presence of monoclonal proteins. A serum/kappa lambda free light chain ratio of < 0.26 or > 1.65 or an abnormal serum/urine immunofixation electrophoresis can indicate amyloid light chain amyloidosis, but alone these factors are usually not definitive for ATTR-CM diagnosis. However, absence of monoclonal proteins and grade 2/3 uptake of 99mTc-pyrophosphate highly indicate AT TR-CM; these factors can be used for diagnosis. TTR mutation does not need to be present for ATTR-CM diagnosis and alone does not strongly indicate this disease; rather, genetic testing for TTR mutations should be conducted to distinguish between hereditary and wild-type ATTR-CM following diagnosis. Learn more about conducting a workup for ATTR-CM. Many neurologic symptoms associated with ATTR-CM overlap with those of other conditions, including Charcot-Marie-Tooth disease. Peripheral neuropathy is a common neurologic symptom of ATTR-CM. Other neurologic symptoms can include autonomic dysfunction, gastroparesis, orthostatic hypotension, erectile dysfunction, and urinary incontinence. As such, ATTR-CM might also be misdiagnosed as other hereditary motor and sensory neuropathies, such as Refsum disease. Therefore, these conditions should be included in a differential diagnosis in patients presenting with neurologic symptoms. Though some with ATTR-CM might experience seizures (usually in cases of patients with leptomeningeal amyloidosis), they are not common. Muscle weakness usually occurs distally in patients with ATTR-CM. Sudden onset of sensory impairment is less common in patients with ATTR-CM and is more characteristic of transthyretin amyloid polyneuropathy. Learn more about performing a differential diagnosis of ATTR-CM. Subcutaneous fat aspiration, which is most commonly used for tissue biopsy, can be sufficient for amyloid detection. While biopsy of samples from organs directly involved in ATTR-CM can be advantageous because sensitivity is reportedly higher, subcutaneous fat aspiration is a less invasive method that can be helpful in diagnosis. However, if tissue biopsy is negative in a patient with a high clinical suspicion of ATTR-CM, or if cardiac scintigraphy is unavailable or negative, endomyocardial biopsy should be performed. It is often used to confirm ATTR-CM diagnosis, along with other forms of cardiac amyloidosis. Learn more about approach considerations for ATTR-CM evaluation.
Yahoo
14-05-2025
- Health
- Yahoo
A NEW HOPE FOR PATIENTS SUFFERING FROM POTENTIALLY FATAL RARE HEART DISEASE: NUHCS IS FIRST IN ASIA TO RECRUIT PATIENTS FOR LANDMARK GENE EDITING CLINICAL TRIAL
The international study explores gene editing therapy to stop the production of proteins causing the disease in ATTR-CM patients SINGAPORE, May 14, 2025 /PRNewswire/ -- While receiving treatment for a car accident ten years ago, Mr Chua learnt that he had an abnormal build-up of protein in his heart vessels. This discovery led to the diagnosis of a condition known as transthyretin amyloid cardiomyopathy (ATTR-CM), a rare disease currently affecting approximately 150 patients in Singapore. ATTR-CM is caused by the build-up of misfolded, deformed transthyretin proteins in the heart, nerves and other organs due to genetic mutation or ageing. Symptoms of this potentially fatal rare disease are often vague and may include numbness in the hands and feet, lethargy and dizziness. If not diagnosed and treated promptly, ATTR-CM can lead to heart failure. Over time, Mr Chua's hands and legs became stiff, and the once active 62-year-old could no longer walk. The subsequent years following his diagnosis were riddled with frequent visits to the hospital due to episodes of heart failure and multiple injuries from falls resulting from nerve issues caused by the disease. Despite being on years of medication, Mr Chua's condition had continued to decline, and his growing need for assistance with simple everyday tasks had greatly affected his spirit. There is currently no cure for this debilitating illness. A new international clinical trial may be set to change the trajectory of this disease for patients suffering from ATTR-CM – including Mr Chua. The MAGNITUDE study involves a single-dose gene editing therapy administered intravenously that will alter the patient's DNA, slowing down the production of the abnormal protein that causes the disease. Novel treatment offers new hope for patients Assistant Professor Lin Weiqin, Clinical Director of the Heart Failure and Cardiomyopathy Programme at the National University Heart Centre, Singapore (NUHCS), is leading the Singapore arm of this trial. He shared that the double-blind study will investigate the impact of the gene editing research medicine Nexiguran Ziclumeran (nex-z, also known as NTLA-2001) on ATTR-CM. "Gene editing therapy has been approved in other countries, for use in some neuro-muscular conditions, cancers and inherited blood disorders. If this trial is successful, it will be the first DNA altering treatment used in the field of adult cardiology and offers new hope to patients living with ATTR-CM," explained Asst Prof Lin, who is also a Senior Consultant at NUHCS. In Asia, the first patient of the double-blind clinical trial was recruited in Singapore and received his infusion in September 2024 at NUHCS. Since then, four more patients have been involved in the study, including Mr Chua, who was the fifth and most recent participant. The gene editing therapy is administered alongside the standard treatment for ATTR-CM as part of the study. While it may take another two to three years to see the outcomes of this study, early results of the trial medication in early phase clinical trials have shown promising results, with "consistent, rapid, and durable reductions" in the abnormal protein that causes ATTR-CM, and minimal side effects.[1] The patients in Singapore have also not reported any side effects thus far. NUHCS is the coordinating site for the Singapore trial. The heart centre is still recruiting patients, who must fulfil the following criteria: Between 18 to 90 years old Diagnosed with heart failure due to ATTR On medication for heart failure and have experienced heart failure in the past year For females, they are only eligible if they can no longer have children. About the National University Heart Centre, Singapore (NUHCS) The National University Heart Centre, Singapore (NUHCS) is an academic, national specialist centre under the National University Health System (NUHS). NUHCS brings together the resources, expertise and capabilities in the areas of Cardiology, Cardiothoracic and Vascular Surgery to better meet the needs of the growing number of patients with heart disease and raise the future generation of medical professionals. As one of two national heart centres in Singapore for the treatment and management of complex cardiovascular diseases, NUHCS offers six core clinical programmes including Heart Failure & Cardiomyopathy, Structural Heart Disease, Acute Coronary Syndrome, Heart Rhythm, Congenital & Structural Heart Disease and Women's Heart Health. The centre has been awarded two institutional Peaks of Excellence for its Minimally-invasive Cardiothoracic Surgery and Aortic Centre Programme, and has been ranked top in Singapore for three consecutive years in 2022, 2023 and 2024 for the specialty of Cardiac Surgery in Newsweek's "World's Best Hospital" Award. Comprising a team of internationally-recognised cardiologists and surgeons from the cardiothoracic and vascular specialties, NUHCS serves as a referral national centre for cardiothoracic and vascular conditions and provides a comprehensive approach to the treatment of these patients. The holistic patient-care approach is backed by leading translational research at the Cardiovascular Research Institute (CVRI) and Cardiovascular Metabolic Translational Program, all of which complements these advanced quaternary clinical services to deliver state-of-the-art treatment solutions to the most challenging heart, lung and circulatory diseases. NUHCS services span across four locations to serve the western and central locations in Singapore: NUHCS at National University Hospital (NUH), Kent Ridge - Main Operations NUHCS Heart Clinic @ Ng Teng Fong General Hospital (NTFGH) NUHCS Heart Clinic @ Jurong Medical Centre (JMC) NUHCS Heart Clinic @ Alexandra Hospital (AH) For more information, visit: [1] Fontana M, Solomon SD, Kachadourian J, Walsh L, Rocha R, Lebwohl D, Smith D, Täubel J, Gane EJ, Pilebro B, Adams D, Razvi Y, Olbertz J, Haagensen A, Zhu P, Xu Y, Leung A, Sonderfan A, Gutstein DE, Gillmore JD. CRISPR-Cas9 Gene Editing with Nexiguran Ziclumeran for ATTR Cardiomyopathy. N Engl J Med. 2024 Dec 12;391(23):2231-2241. doi: 10.1056/NEJMoa2412309. Epub 2024 Nov 16. PMID: 39555828. 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