Cardiac amyloidosis (CA) involves the deposition of misfolded proteins in the heart, most commonly light-chains (AL) or transthyretin (ATTR). Advancements in non-invasive diagnostics have challenged the classification of CA as a rare disease. The Cardiac Amyloidosis RegistRY (CARRY) provides updated insights into CA's epidemiology, diagnosis, and clinical features. CARRY is a prospective, multicenter study across 20 hospitals in Tuscany and Umbria. All patients aged ≥18 years with suspected CA were enrolled between January and December 2022. Baseline demographic, clinical, laboratory, and imaging data were collected, including all tests required to confirm or rule out CA diagnosis. Among 553 patients with complete data (median age 79 years [interquartile range, IQR, 74-84], 70 % male), 87 % reported mild dyspnea, 32 % had a history of heart failure, and one-third reported carpal tunnel syndrome. Elevated cardiac biomarkers were prevalent, with a median NT-proBNP of 1015 ng/L (IQR 275-3198). Most patients exhibited a heart failure with preserved ejection fraction phenotype. No significant differences in clinical features were found between patients from university (referral centers) and non-university hospitals, though referral centers more often reported patients with hematologic disorders. Echocardiographic signs of overt CA were more frequent in non-university centers. The CARRY registry highlights the clinical characteristics of patients with suspected CA, revealing that despite educational efforts, suspicion remains biased towards older patients with advanced disease. Increased awareness and earlier diagnosis, particularly with available disease-modifying therapies, are critical for improving outcomes.

Variant transthyretin amyloidosis (ATTRv) is a rare multisystemic disorder caused by mutations in the transthyretin (TTR) gene. The aim of the present work was to describe the clinical profile of asymptomatic carriers (AC) and Coutinho stage 1 ATTRv patients in Spain. National, multicentre, cross-sectional study that included 86 AC and 19 patients diagnosed in the previous 12 months to enrolment. Clinical and demographical data, TTR gene mutations, red flags anamnesis, neurological and cardiological assessments were collected. The mean age of patients was 56.8 years at onset and 58.6 years at diagnosis; 53% of patients and 51% of AC were from non-endemic areas. Val50Met was the most frequent mutation in both groups. Neuropathy impairment score data (mean 17.7 ± 20.5) and small-fibre function in lower limbs assessed with SUDOSCAN revealed that patients were diagnosed at early stages of neurological impairment. Peripheral polyneuropathy (84.2%), autonomic neuropathy (73.7%), cardiac (63.2%) and gastrointestinal (47.4%) alterations were the most common symptoms in patients. Autonomic neuropathy, gastrointestinal impairment, carpal tunnel syndrome, cardiac and ocular alterations were potentially related to ATTRv in the AC group. The EMPATIa study provides a detailed description of AC and Coutinho stage 1 ATTRv patients across Spain, confirming the multisystemic clinical profile of the disease. This study reveals a diagnosis delay around 1.8 years, highlighting the importance of a profound disease awareness to reach a diagnose in earlier stages of neurological impairment.

Transthyretin cardiac amyloidosis (ATTR-CA) is a rare and potentially fatal disease caused by the accumulation of insoluble transthyretin (TTR) amyloid fibrils in the heart. The symptoms of ATTR-CA are often non-specific, often leading to underdiagnosis. Early diagnosis and treatment have a significant impact on disease progression and mortality. In this case we report a 73-year-old male presented with dyspnea on exertion. The patient had a medical history of peripheral neuropathy, bilateral carpal tunnel syndrome, spinal fusion, and a family history of coronary artery disease. Upon his presentation at the Cardiology department, cardiac echo study revealed left and right ventricular hypertrophy with pulmonary hypertension, diastolic dysfunction and a restrictive pattern. Because of the high probability of amyloidosis, the patient underwent a technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) bone scintigraphic study, which confirmed the diagnosis of ATTR-CA. Transthyretin gene sequencing analysis revealed the rare p. Pro24Ser pathogenic variant. Final diagnosis was ATTR-CA associated with the proline replaced by serine at position 24 (Pro24Ser) TTR variant, which is rare and only a few cases have been reported worldwide. The patient was treated with tafamidis and inotersen and followed up. This case highlights the importance of considering amyloidosis as a differential diagnosis for non-specific symptoms and the need for early diagnosis and management of ATTR-CA.

Although transthyretin cardiac amyloidosis (ATTR-CA) is often underdiagnosed, clinical suspicion is essential for early diagnosis. The aim of this study was to develop and validate a feasible prediction model and score to facilitate the diagnosis of ATTR-CA. This retrospective multicenter study enrolled consecutive patients who underwent 99mTc-DPD scintigraphy for suspected ATTR-CA. ATTR-CA was diagnosed if Grade 2 or 3 cardiac uptake was evidenced on 99mTc-DPD scintigraphy in the absence of a detectable monoclonal component or by demonstration of amyloid by biopsy. A prediction model for ATTR-CA diagnosis was developed in a derivation sample of 227 patients from 2 centers using multivariable logistic regression with clinical, electrocardiography, analytical, and transthoracic echocardiography variables. A simplified score was also created. Both of them were validated in an external cohort (n = 895) from 11 centers. The obtained prediction model combined age, gender, carpal tunnel syndrome, interventricular septum in diastole thickness, and low QRS interval voltages, with an area under the curve (AUC) of 0.92. The score had an AUC of 0.86. Both the T-Amylo prediction model and the score showed a good performance in the validation sample (ie, AUC: 0.84 and 0.82, respectively). They were tested in 3 clinical scenarios of the validation cohort: 1) hypertensive cardiomyopathy (n = 327); 2) severe aortic stenosis (n = 105); and 3) heart failure with preserved ejection fraction (n = 604), all with good diagnostic accuracy. The T-Amylo is a simple prediction model that improves the prediction of ATTR-CA diagnosis in patients with suspected ATTR-CA.

Carpal tunnel syndrome (CTS) is a very common clinical syndrome manifested by signs and symptoms of irritation of the median nerve at the carpal tunnel in the wrist. Direct and indirect costs of CTS are substantial, with estimated costs of two billion US dollars for CTS surgery in the USA in 1995 alone. Local corticosteroid injection has been used as a non-surgical treatment for CTS many years, but its effectiveness is still debated. To evaluate the benefits and harms of corticosteroids injected in or around the carpal tunnel for the treatment of carpal tunnel syndrome compared to no treatment or a placebo injection. We used standard, extensive Cochrane search Methods. The searches were 7 June 2020 and 26 May 2022. We included randomised controlled trials (RCTs) or quasi-randomised trials of adults with CTS that included at least one comparison group of local injection of corticosteroid (LCI) into the wrist and one group that received a placebo or no treatment. We used standard Cochrane methods. Our primary outcome was 1. improvement in symptoms at up to three months of follow-up. Our secondary outcomes were 2. functional improvement, 3. improvement in symptoms at greater than three months of follow-up, 4. improvement in neurophysiological parameters, 5. improvement in imaging parameters, 6. requirement for carpal tunnel surgery, 7. improvement in quality of life and 8. We used GRADE to assess the certainty of evidence for each outcome. We included 14 trials with 994 participants/hands with CTS. Only nine studies (639 participants/hands) had useable data quantitatively and in general, these studies were at low risk of bias except for one quite high-risk study. The trials were conducted in hospital-based clinics across North America, Europe, Asia and the Middle East. All trials used participant-reported outcome measures for symptoms, function and quality of life. There is probably an improvement in symptoms measured at up to three months of follow-up favouring LCI (standardised mean difference (SMD) -0.77, 95% confidence interval (CI) -0.94 to -0.59; 8 RCTs, 579 participants; moderate-certainty evidence). Up to six months this was still evident favouring LCI (SMD -0.58, 95% CI -0.89 to -0.28; 4 RCTs, 234 participants/hands; moderate-certainty evidence). There is probably an improvement in function measured at up to three months favouring LCI (SMD -0.62, 95% CI -0.87 to -0.38; 7 RCTs, 499 participants; moderate-certainty evidence). We are uncertain if there is a difference in median nerve DML at up to three months of follow-up (mean difference (MD) -0.37 ms, 95% CI -0.75 to 0.02; 6 RCTs, 359 participants/hands; very low-certainty evidence). The requirement for surgery probably reduces slightly in the LCI group at one year (risk ratio 0.84, 95% CI 0.72 to 0.98; 1 RCT, 111 participants, moderate-certainty evidence). Quality of life, measured at up to three months of follow-up using the Short-Form 6 Dimensions questionnaire (scale from 0.29 to 1.0; higher is better) probably improved slightly in the LCI group (MD 0.07, 95% CI 0.02 to 0.12; 1 RCT, 111 participants; moderate-certainty evidence). Adverse events were uncommon (low-certainty evidence). One study reported 2/364 injections resulted in severe pain which resolved over "several weeks" and 1/364 injections caused a "sympathetic reaction" with a cool, pale hand that completely resolved in 20 minutes. One study (111 participants) reported no serious adverse events, but 65% of LCI-injected and 16% of the placebo-injected participants experienced mild-to-moderate pain lasting less than two weeks. About 9% of participants experienced localised swelling lasting less than two weeks. Four studies (229 participants) reported that they experienced no adverse events in their studies. Three studies (220 participants) did not specifically report adverse events. Local corticosteroid injection is effective for the treatment of mild and moderate CTS with benefits lasting up to six months and a reduced need for surgery up to 12 months. Where serious adverse events were reported, they were rare.