Tafamidis improves myocardial longitudinal strain in A97S transthyretin cardiac amyloidosis.

Background: Transthyretin cardiomyopathy (ATTR-CM) is a debilitating disease that has received much attention since the emergence of novel treatments. The Transthyretin Cardiomyopathy Clinical Trial showed that tafamidis, a transthyretin tetramer stabilizer, effectively reduced the declines in functional capacity and quality of life. However, Ala97Ser (A97S) hereditary ATTR-CM is underrepresented in major ATTR-CM tafamidis trials. Objectives: We aim to investigate the change in global longitudinal strain (GLS) of A97S ATTR-CM patients after 12 months of tafamidis treatment. Methods: We retrospectively analysed a prospective cohort of patients with A97S ATTR-CM who received tafamidis meglumine (61 mg/day) at the National Taiwan University Hospital. Echocardiography with speckle tracking strain analysis was performed at baseline and 12 months after treatment. Results: In all, 20 patients were included in the cohort. The baseline left ventricular ejection fraction (LVEF) and interventricular septum (IVS) thickness were 59.20 ± 13.23% and 15.10 ± 3.43 mm, respectively. After 12 months of tafamidis treatment, the LVEF and IVS were 61.83 ± 15.60% (p = 0.244) and 14.59 ± 3.03 mm (p = 0.623), respectively. GLS significantly improved from -12.70 ± 3.31% to -13.72 ± 3.17% (p = 0.048), and longitudinal strain (LS) in apical and middle segments significantly improved from -16.05 ± 4.82% to -17.95 ± 3.48% (p = 0.039) and -11.89 ± 4.38% to -13.58 ± 3.12% (p = 0.039), respectively. Subgroup analysis showed that patients with LVEF < 50% had a better treatment response and improvement in GLS. The patients with an IVS ⩾ 13 mm had an improvement in two-chamber LS from -10.92 ± 4.25% to -13.15 ± 3.87% (p = 0.042) and an improvement in apical left ventricular LS from -15.30 ± 5.35% to -17.82 ± 3.99% (p = 0.031). Conclusion: Tafamidis significantly improved GLS, and particularly apical and middle LS in A97S ATTR-CM patients.

Tafamidis improves myocardial longitudinal strain in A97S transthyretin cardiac amyloidosis Transthyretin cardiomyopathy (ATTR-CM) is a severe heart condition that has gained attention due to recent advancements in treatments. One of these treatments, called tafamidis, has been shown to be effective in maintaining heart function and quality of life. However, there has been limited research on a specific genetic variation of ATTR-CM: A97S. Our aim was to determine whether A97S ATTR-CM patients experienced improved heart function after one year of tafamidis treatment. We conducted this study at the National Taiwan University Hospital, where we enrolled 20 A97S ATTR-CM patients. We used echocardiography to evaluate their heart function, focusing on a parameter called global longitudinal strain. The results showed that after one year of tafamidis treatment, these patients experienced a significant improvement in their global longitudinal strain, particularly in the apical and middle regions of the heart. In conclusion, tafamidis appears to be beneficial for A97S ATTR-CM patients by enhancing their heart's global longitudinal strain, which is a positive sign for their cardiac health.

Use of Technetium-99m-Pyrophosphate Single-Photon Emission Computed Tomography/Computed Tomography in Monitoring Therapeutic Changes of Eplontersen in Patients With Hereditary Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: Hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) is a progressive and fatal disease. Recent evidence indicates that bone scintigraphy may serve as a tool to monitor the effectiveness of hATTR-CM treatment. The objective of this study was to examine how eplontersen therapy influences the semiquantitative uptake of technetium-99m-pyrophosphate in individuals diagnosed with hATTR-CM. METHODS AND RESULTS: We retrospectively analyzed a prospective cohort from the NEURO-TTRansform trial, including patients with hATTR-CM receiving eplontersen (45 mg/4 weeks). A control group comprised patients with hATTR-CM who had not received eplontersen, inotersen, tafamidis, or patisiran. Technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography was conducted at baseline and during follow-up. Thirteen patients with hATTR-CM were enrolled, with 6 receiving eplontersen and 7 serving as the control group. The median follow-up time was 544 days. The eplontersen group exhibited a significant decrease in volumetric heart and lung ratio (3.774 to 2.979, P=0.028), whereas the control group showed no significant change (4.079 to 3.915, P=0.237). Patients receiving eplontersen demonstrated a significantly greater reduction in volumetric heart and lung ratio compared with the control group (-20.7% versus -3.4%, P=0.007). CONCLUSIONS: The volumetric heart and lung ratio used to quantify technetium-99m-pyrophosphate uptake showed a significant reduction subsequent to eplontersen treatment in individuals diagnosed with hATTR-CM. These findings suggest the potential efficacy of eplontersen in treating hATTR-CM and highlight the value of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography as a tool for monitoring therapeutic effectiveness.

Efficacy of Tafamidis in Patients with Ala97Ser Hereditary Transthyretin Cardiac Amyloidosis: A Six-Month Follow-Up Study.

Background: Hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal disease. A97S (p.Ala117Ser) is the most common transthyretin genetic mutation in Taiwan. Tafamidis is a transthyretin stabilizer, and it has been shown to improve outcomes. However, its effect on A97S ATTR-CM subtypes remains unknown. Objectives: This study aimed to investigate the efficacy of tafamidis in patients with hereditary A97S ATTR-CM after 6 months of treatment. Methods: We retrospectively analyzed ATTR-CM patients who received tafamidis (61 mg/day) treatment at National Taiwan University Hospital. Functional status, biochemistry and echocardiography were measured at baseline and after 6 months of tafamidis treatment. The outcome measure was to compare the N-terminal pro-brain natriuretic peptide (NT-proBNP) level at baseline and after 6 months of tafamidis treatment. Results: Twenty patients were enrolled in this study. Their mean age was 63.0 ± 5.8 years and 75% were men. The baseline left ventricular (LV) mass index was 200.9 ± 63.9 g/m2, and the baseline LV ejection fraction was 58.9 ± 13.5%. After 6 months of treatment, the log NT-proBNP level significantly improved from 2.9 ± 0.6 to 2.7 ± 0.5 (p = 0.036). Subgroup analysis showed that the LV posterior wall thickness and left atrial diameter were significantly higher in the patients with improved NT-proBNP, suggesting the benefits of tafamidis for ATTR-CM patients with severe cardiac involvement. Conclusions: The patients with hereditary A97S ATTR-CM in this study had decreased levels of NT-proBNP after 6 months of tafamidis treatment, and this reduction was especially pronounced in those with more severe cardiac involvement.

Coexistence of atrioventricular accessory pathways and drug-induced type 1 Brugada pattern.

BACKGROUND: Atrial arrhythmias, particularly atrioventricular nodal reentrant tachycardia, can coexist with drug-induced type 1 Brugada electrocardiogram (ECG) pattern (DI-Type1-BrP). The present study was designed to determine the prevalence of DI-Type1-BrP in patients with atrioventricular accessory pathways (AV-APs) and to investigate the clinical, electrocardiographic, electrophysiologic, and genetic characteristics of these patients. METHODS: One-hundred twenty-four consecutive cases of AV-APs and 84 controls underwent an ajmaline challenge test to unmask DI-Type1-BrP. Genetic screening and analysis was performed in 55 of the cases (19 with and 36 without DI-Type1-BrP). RESULTS: Patients with AV-APs were significantly more likely than controls to have a Type1-BrP unmasked (16.1 vs 4.8%, P = 0.012). At baseline, patients with DI-Type1-BrP had higher prevalence of chest pain, QR/rSr' pattern in V1 and QRS notching/slurring in V2 and aVL during preexcitation, rSr' pattern in V1 -V2 , and QRS notching/slurring in aVL during orthodromic atrioventricular reentrant tachycardia (AVRT) compared to patients without DI-Type1-BrP. Abnormal QRS configuration (QRS notching/slurring and/or fragmentation) in V2 during preexcitation was present in all patients with DI-Type1 BrP. The prevalence of spontaneous preexcited atrial fibrillation (AF) and history of AF were similar (15% vs 18.3%, P = 0.726) in patients with and without DI-Type1-BrP, respectively. The prevalence of mutations in Brugada-susceptibility genes was higher (36.8% vs 8.3%, P = 0.02) in patients with DI-Type1-BrP compared to patients without DI-Type1-BrP. CONCLUSIONS: DI-Type1-BrP is relatively common in patients with AV-APs. We identify 12-lead ECG characteristics during preexcitation and orthodromic AVRT that point to an underlying type1-BrP, portending an increased probability for development of malignant arrhythmias.