Amyloid Cardiomyopathy Research Articles

Tracking the Preclinical Progression of Transthyretin Amyloid Cardiomyopathy Using Artificial Intelligence-Enabled Electrocardiography and Echocardiography.

The diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) requires advanced imaging, precluding large-scale pre-clinical testing. Artificial intelligence (AI)-enabled transthoracic echocardiography (TTE) and electrocardiography (ECG) may provide a scalable strategy for pre-clinical monitoring. This was a retrospective analysis of individuals referred for nuclear cardiac amyloid testing at Yale-New Haven Health System (YNHHS, internal cohort) and Houston Methodist Hospitals (HMH, external cohort). Deep learning models trained to discriminate ATTR-CM from age/sex-matched controls on TTE videos (AI-Echo) and ECG images (AI-ECG) were deployed to generate study-level ATTR-CM probabilities (0-100%). Longitudinal trends in AI-derived probabilities were examined using age/sex-adjusted linear mixed models, and their discrimination of future disease was evaluated across preclinical stages. Among 984 participants at YNHHS (median age 74 years, 44.3% female) and 806 at HMH (69 years, 34.5% female), 112 (11.4%) and 174 (21.6%) tested positive for ATTR-CM, respectively. Across cohorts and modalities, AI-derived ATTR-CM probabilities from 7,352 TTEs and 32,205 ECGs diverged as early as 3 years before diagnosis in cases versus controls ( p time(x)group interaction ≤ 0.004). Among those with both AI-Echo and AI-ECG available one-to-three years before nuclear testing (n=433 [YNHHS] and 174 [HMH]), a double-negative screen at a 0.05 threshold (164 [37.9%] and 66 [37.9%], vs all else) had 90.9% and 85.7% sensitivity (specificity of 40.3% and 41.2%), whereas a double-positive screen (78 [18.0%] and 26 [14.9%], vs all else) had 85.5% and 88.9% specificity (sensitivity of 60.6% and 42.9%). AI-enabled echocardiography and electrocardiography may enable scalable risk stratification of ATTR-CM during its pre-clinical course.

Cardiac diagnoses and long-term outcomes in ring-like late gadolinium enhancement evaluated by cardiac magnetic resonance.

Non-ischaemic ring-like late gadolinium enhancement (LGE) in the left ventricle (LV) detected by cardiac magnetic resonance (CMR) is an emerging biomarker associated with adverse outcomes. Data regarding ring-like LGE are limited to small patient cohorts. We aimed to assess the prevalence of ring-like LGE, its association with morpho-functional phenotypes, aetiologic background, and prognostic implications. This single-centre observational retrospective study included consecutive patients undergoing LGE-CMR between 2002 and 2024. Ring-like LGE was defined as continuous enhancement in ≥3 adjacent segments. Ischaemic and amyloid cardiomyopathies (CMPs) were excluded. Clinical records were reviewed for etiologic diagnosis and clinical outcomes. The primary endpoint was a composite of all-cause mortality, heart transplantation, or LV assist device implantation. The secondary endpoint included sustained ventricular tachycardia, appropriate implantable cardioverter-defibrillator therapies, or sudden cardiac death. Among 14 091 unique patients who underwent LGE-CMR, ring-like LGE was identified in 152 patients (1.1%) with a median number of 10 segments, mostly involving the inferolateral segments. The most frequent morpho-functional phenotypes were dilated and non-dilated LV CMP. Genetic testing identified likely pathogenic/pathogenic variants in 59 (58.4%) patients, affecting both desmosomal and non-desmosomal genes. Inflammatory CMP was diagnosed in 15.8%. Other rare aetiologies included genetic neuromuscular diseases and inborn errors of metabolism. Primary and secondary endpoints occurred in 17.8 and 17.1%, respectively, over a median follow-up of 3 years. Ring-like LGE is an uncommon, non-disease-specific feature found in various morpho-functional CMP phenotypes. It is associated with frequent genetically determined aetiologies and a high burden of adverse outcomes.

Guideline-Directed Medical Therapy for Heart Failure in Transthyretin Amyloid Cardiomyopathy.

Cardiac amyloidosis is an underdiagnosed cause of infiltrative cardiomyopathy, leading to heart failure across the spectrum of ejection fractions. Although there are approved disease-modulating therapies for the transthyretin subtype (transthyretin amyloid cardiomyopathy [ATTR-CM]), the role of heart failure medications remains uncertain and challenging in clinical practice. Their effects on clinical outcomes, such as mortality and hospitalization, are unknown for ATTR-CM. This review aims to explore the use of these medications in ATTR-CM, considering the disease's stage and patient-specific issues, such as fluid homeostasis, autonomic dysfunction, conduction disorders, low and fixed stroke volumes, and decreased functional capacity. As our understanding of this condition deepens, it is important to reassess the impact of contemporary heart failure medication in ATTR-CM. Finally, the relevance of guideline recommendations for heart failure drugs based on left ventricular ejection fraction should be reconsidered in the context of ATTR-CM.

Silencers versus stabilizers in amyloid cardiomyopathy. Are we asking the wrong questions?

Silencers versus stabilizers in amyloid cardiomyopathy. Are we asking the wrong questions?

Effects of tafamidis on serial [99mTc]Tc-DPD scintigraphy in transthyretin amyloid cardiomyopathy

PurposeThe relevance of repetitive [99mTc]Tc-DPD scintigraphy in wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) remains unclear. We investigated the impact of tafamidis on cardiac [99mTc]Tc-DPD uptake, clinical, and laboratory markers at 6 and 12 months, and correlated 12 months [99mTc]Tc-DPD uptake regression with survival.MethodsThis single-center study enrolled 39 ATTRwt-CM patients. Upon treatment initiation with tafamidis, patients underwent follow-up [99mTc]Tc-DPD scintigraphy, and clinical and laboratory evaluations at 6 months (n = 6) and 12 months (n = 13), or both (n = 20).ResultsTafamidis resulted in a significant decline in Perugini score (6 months p = 0.008, 12 months p < 0.001), and (semi-)quantitative [99mTc]Tc-DPD uptake (total cardiac uptake: baseline 816 [522–933] cps, vs. 6 months 634 [502–734] cps, p = 0.003, vs. 12 months 523 [108–754] cps, p = 0.001). Clinical and laboratory improvements were observed (NYHA: 6 months p = 0.007, 12 months p = 0.033; NT-proBNP: baseline 2586 [1271–5561] ng/L, vs. 6 months 2526 [1109–4786] ng/L, p = 0.016, vs. 12 months 2340 [1411–4749] ng/L, p = 0.012). In Kaplan–Meier analysis, a decrease in right ventricular [99mTc]Tc-DPD tracer uptake equal to or greater than the median value at 12 months (-30%) was associated with improved survival (log-rank p = 0.021).ConclusionsTafamidis in ATTRwt-CM resulted in significant reductions of cardiac [99mTc]Tc-DPD uptake, NYHA class, and cardiac biomarkers at 6 and 12 months. Regression of right ventricular [99mTc]Tc-DPD uptake at 12 months was associated with improved survival.

Artificial intelligence-based cardiac transthyretin amyloidosis detection and scoring in scintigraphy imaging: multi-tracer, multi-scanner, and multi-center development and evaluation study

IntroductionProviding tools for comprehensively evaluating scintigraphy images could enhance transthyretin amyloid cardiomyopathy (ATTR-CM) diagnosis. This study aims to automatically detect and score ATTR-CM in total body scintigraphy images using deep learning on multi-tracer, multi-scanner, and multi-center datasets.MethodsIn the current study, we employed six datasets (from 12 cameras) for various tasks and purposes. Dataset #1 (93 patients, 99mTc-MDP) was used to develop the 2D-planar segmentation and localization models. Dataset #2 (216 patients, 99mTc-DPD) was used for the detection (grade 0 vs. grades 1, 2, and 3) and scoring (0 and 1 vs. grades 2 and 3) of ATTR-CM. Datasets #3 (41 patients, 99mTc-HDP), #4 (53 patients, 99mTc-PYP), and #5 (129 patients, 99mTc-DPD) were used as external centers. ATTR-CM detection and scouring were performed by two physicians in each center. Moreover, Dataset #6 consisting of 3215 patients without labels, was employed for retrospective model performance evaluation. Different regions of interest were cropped and fed into the classification model for the detection and scoring of ATTR-CM. Ensembling was performed on the outputs of different models to improve their performance. Model performance was measured by classification accuracy, sensitivity, specificity, and AUC. Grad-CAM and saliency maps were generated to explain the models’ decision-making process.ResultsIn the internal test set, all models for detection and scoring achieved an AUC of more than 0.95 and an F1 score of more than 0.90. For detection in the external dataset, AUCs of 0.93, 0.95, and 1 were achieved for datasets 3, 4, and 5, respectively. For the scoring task, AUCs of 0.95, 0.83, and 0.96 were achieved for these datasets, respectively. In dataset #6, we found ten cases flagged as ATTR-CM by the network. Out of these, four cases were confirmed by a nuclear medicine specialist as possibly having ATTR-CM. GradCam and saliency maps showed that the deep-learning models focused on clinically relevant cardiac areas.ConclusionIn the current study, we developed and evaluated a fully automated pipeline to detect and score ATTR-CM using large multi-tracer, multi-scanner, and multi-center datasets, achieving high performance on total body images. This fully automated pipeline could lead to more timely and accurate diagnoses, ultimately improving patient outcomes.

Atrial fibrillation burden and management in cardiomyopathies: Current evidence and unmet needs.

Atrial fibrillation burden and management in cardiomyopathies: Current evidence and unmet needs.

Suspicion and referral of patients with transthyretin amyloid cardiomyopathy: Recommendations by a Portuguese multidisciplinary expert panel.

Suspicion and referral of patients with transthyretin amyloid cardiomyopathy: Recommendations by a Portuguese multidisciplinary expert panel.

Portuguese recommendations for the management of transthyretin amyloid cardiomyopathy (Part 1 of 2): Screening, diagnosis and treatment. Developed by the Task Force on the management of transthyretin amyloid cardiomyopathy of the Working Group on Myocardial and Pericardial Diseases of the Portuguese Society of Cardiology.

Portuguese recommendations for the management of transthyretin amyloid cardiomyopathy (Part 1 of 2): Screening, diagnosis and treatment. Developed by the Task Force on the management of transthyretin amyloid cardiomyopathy of the Working Group on Myocardial and Pericardial Diseases of the Portuguese Society of Cardiology.

Left atrial mechanics and left ventricular function in cardiac amyloidosis patients treated with tafamidis

Abstract Introduction and aims Patients with amyloid cardiomyopathy (ATTR-CM) present with a restrictive phenotype characterized by decreased ventricular compliance and increased filling pressures, with progressive loss of atrial function and increased stiffness, which are associated with poor clinical outcomes. Tafamidis improves clinical outcomes and slows disease progression but its effects in left ventricle (LV) and atrium (LA) mechanics are still unclear, with recent studies (reference 1.) suggesting improvement of LA function (as assesses by LA strain [LAS]) in patients with sinus rythm (SR). Our study aimed to characterize the 1-year evolution of LV function and LA mechanics in ATTR-CM patients treated with tafamidis. Methods We prospectively evaluated a cohort of patients with ATTR-CM treated with tafamidis in a single-centre. Results Out of 41 patients treated, 13 were excluded due to incomplete follow-up or poor quality of echocardiographic images that precluded LAS analysis. A total of 28 patients (75% male) were included, with a mean age of 80 ± 10 years at the start of treatment and a median follow up of 14 months. 11 pts (39%) were in sinus rhythm (SR group) and 17 (61%) were not (non-SR group). At the start of the treatment with tafamidis, mean LV ejection fraction (LVEF) was 55.5 ± 11.4%, GLS was -10.7 ± 4.3%, E/e’ 17.2 ± 5.4 and indexed LA volume (LAVi) 47.4 ± 15.3 mL/m2. Median NTproBNP was 2031 (3143) pg/mL and pts walked 313 ± 121m on the 6-minute walk test (6MWT). Regarding LAS, there was significant reduction in all atrial functional components in both SR (LAS reservoir 13.1 ± 12, LAS conduit -6.5 ± 4.2, LA contraction -6.6 ± 3.6) and non-SR groups (LAS reservoir 5.1 ± 3.6) as well as significantly increased LA stiffness (SR – 1.4 ± 0.9, non-SR – 6.1 ±6.0). Our analysis showed stabilization, with no statistically significant differences in LVEF, GLS, diastolic function parameters, LAS or LA stiffness, as well as NTproBNP and 6MWT after 1-year treatment with tafamidis (tables 1 and 2). We found a moderate correlation between LAS contraction and NTproBNP in the SR group (r=0.650, p=0.031) – meaning that worse (less negative) LAS contraction associated with higher NTproBNP values – despite there being no correlation between other echocardiographic variables ante NTproBNP or 6MWT. Conclusions In our cohort of patients, patients presented with significantly reduced atrial function and increased stiffness. 12-month treatment with tafamidis allowed stabilization of LA and LV performance, as well as of NTproBNP and 6MWT. We found a moderate correlation between LA contraction objectively evaluated by strain analysis and NTproBNP in SR patients, highlighting the importance of LA mechanical contraction preservation in patients with a restrictive cardiomyopathy phenotype.

Valvular heart disease in transthyretin cardiac amyloidosis

Abstract Introduction Amyloidosis cardiomyopathy (CM) is known to be associated with valvular heart disease (VHD) and particularly with aortic stenosis (AS). However, previous studies included both immunoglobulin light-chain CM and transthyretin amyloid CM (ATTR-CM), with limited data focussing specifically on ATTR-CM. Furthermore, VHD assessment was mostly limited to isolated significant VHD, and the difference in outcome between isolated and multiple VHD is largely unknown. Aim To evaluate the prevalence and prognostic value of significant VHD in ATTR-CM patients, including the differences in outcome between isolated and multiple significant VHD, with or without AS. Methods Patients with ATTR-CM were retrospectively included in this multicentric study. Significant VHD was defined as at least moderate VHD. The study endpoint was a composite of heart failure hospitalisations and all-cause death. Results A total of 694 ATTR-CM patients (mean age 75 ±13 years, 74% male) were included, and 302 (44%) presented with significant VHD (Figure 1). These patients were older (81±9 vs. 71±13, p&amp;lt;0. 001), had more cardiovascular risk factors, lower left ventricular ejection fraction (50±12 vs. 54±12, p&amp;lt;0.001) and more pulmonary arterial hypertension (76% vs. 45%, p&amp;lt;0.001), as compared to patients without significant VHD. Among patients with significant VHD, only 98 patients had VHD including AS (isolated AS in 45%; multiple VHD with AS in 55%), while the majority (n=204) had VHD without AS (isolated in 64%, multiple VHD in 36%) (Figure 1). During a median follow-up of 16 (6 - 33) months, 214 (31%) patients reached the study endpoint. Univariable Cox regression analysis identified significant VHD as a predictor of worse outcomes (HR: 3.486; 95% CI: 2.627 - 4.626; p &amp;lt; 0.001), which remained significant in the multivariable Cox regression analysis (HR: 1.879;95%CI:1.182 - 2.987;p=0.008), after adjusting for transthyretin amyloid cardiomyopathy phenotype, disease-modifying treatment, coronary artery disease, atrial fibrillation, renal function, New York Heart Association III-IV, polyneuropathy, electrocardiographic abnormalities, left ventricular stroke volume, interventricular septum thickness, left atrial dilatation, tricuspid annular plane systolic excursion, and arterial pulmonary hypertension(Figure2). Further stratification based on the presence of significant AS, and according to isolated or multiple VHD, revealed that patients isolated significant AS (HR:2.399;95%CI 1.179 – 4.884;p=0.016), and patients with multiple VHD including significant AS, had the highest risk for adverse outcomes (HR:3.542; 95%CI: 1.809 - 6.935;p&amp;lt;0.001)(Figure 2). Conclusion In ATTR-CM, significant VHD is strongly associated with poor prognosis, with the highest risk for adverse events in patients with significant multiple VHD including AS. These findings underscore the importance of VHD assessment for risk stratification and possibly targeted treatment in this patient population. The distribution of significant VHD.

Patient Journey to Transthyretin Cardiac Amyloidosis Diagnosis ― A Japanese Claims Database Study ―

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) in older adults. Delayed ATTR-CM diagnosis may result in more advanced symptoms. This study describes the journey of Japanese patients with ATTR-CM. This retrospective non-interventional study used the DeSC Healthcare database. Patients aged ≥18 years at the index date (date when ATTR-CM was first diagnosed or date of first tafamidis 80 mg prescription, whichever was earlier) and who had received ≥1 tafamidis 80 mg prescription or ≥1 specific ATTR-CM diagnosis, excepting "suspected diagnosis", at any time between April 1, 2014 and August 31, 2021 were included. The median age of patients was 79.0 years, and 79.9% (n=239) were male. The most frequently observed comorbidities defined as indicating the onset of ATTR-CM were HF (87.9%), atrial fibrillation/atrial flutter (50.2%), and conduction disorders (17.2%), with a median time from onset to index date of 15.5, 14.0, and 9.0 months for each comorbidity, respectively. Lumbar spinal stenosis (23.9%), neuropathy (13.0%), and carpal tunnel syndrome (7.5%) were common extracardiac symptoms, with a median time from the appearance of these symptoms to index date of 19.0, 5.0, and 18.0 months, respectively. There was a delay between the appearance of cardiac and extracardiac comorbidities of ATTR-CM and its diagnosis in real-world Japanese clinical settings, emphasizing the need for early diagnosis of ATTR-CM.

Diagnostic Utility of Relative Apical Sparing Index in Cardiac Amyloidosis Subtypes: A Comparative Study of Immunoglobulin Light Chain and Transthyretin Amyloid Cardiomyopathy.

Speckles tracking echocardiography imaging enables clinicians to detect subtle systolic dysfunction. The aim of the present study was to elucidate the differences in speckle tracking echocardiographic findings between immunoglobulin light chain amyloid cardiomyopathy (AL-CM) and transthyretin amyloid cardiomyopathy (TTR-CM). The patients with a confirmed diagnosis of cardiac amyloidosis through cardiac biopsy from March 2013 to October 2022 were included. The relative apical sparing index (RASI) was calculated using speckle tracking echocardiography by the following equation; average apical strain/(average basal strain+mid strain). The final study population consisted of 35 patients with cardiac amyloidosis (AL-CM: 10 patients, TTR-CM: 25 patients). The mean age was 74±12years. Although both subgroups had a gradual change of strain values from basal to apical segments, RASI was significantly lower in AL-CM compared to TTR-CM (0.92±0.29 vs. 1.46±0.53, p=0.001). A RASI cutoff value of <1.0 proved useful in differentiating the diagnosis of AL-CM from TTR-CM (sensitivity: 81%, specificity: 70%, AUC: 0.82). A significant positive correlation with left ventricular mass index and RASI was found in AL-CM, but not in TTR-CM. The apical sparing phenomenon was more remarkable in TTR-CM compared with AL-CM. RASI might be useful for the discrimination of cardiac amyloidosis subtypes. There was a difference in the relationship of RASI with left ventricular wall thickness between the cardiac amyloidosis subtypes.

Comparison of in-clinic assessment of 6MWT by conventional method and using wearable sensors for patients with ATTR-CM.

The 6-minute walk test (6MWT) is used to assess submaximal exercise capacity in clinical trials. Conducting the 6MWT can be challenging when patients cannot visit the clinic due to physical/travel limitations. This pilot study assessed the feasibility of conducting the 6MWT using wearable sensors for patients with transthyretin amyloid cardiomyopathy. Participants were enrolled in the phase 3 ATTRibute-CM trial. Sensors were positioned on patients' feet and lower back during the 6MWT. The 6-minute walk distance (6MWD) was compared with the distance measured by a trained observer during a concurrent conventional test. Pearson and concordance correlation coefficients were estimated. Twelve participants from five centers participated; 11had evaluable data. Mean 6MWD was 330.3 m (conventional method) and 335.1 m (wearable sensors); mean difference (SD) was 4.7 m (10.95). Pearson and concordance correlation coefficients for 6MWD were 0.998 (95% CI: 0.992-0.999) and 0.997 (95% CI: 0.991-0.999), respectively. The 6MWD measured using wearable sensors and by the conventional method were closely correlated. Conducting the 6MWT with wearable sensors may be feasible and as reliable as the conventional method in a monitored clinic setting. Whether at-home 6MWD measured by wearable sensors correlates with in-clinic monitoring deserves further study. ClinicalTrials.gov identifier is NCT03860935.

The Accuracy of Technetium-99m Pyrophosphate Imaging in Diagnosing Transthyretin Cardiac Amyloidosis and Its Impact on Patient Management.

This review evaluates recent advancements in Technetium-99m pyrophosphate (99mTc-PYP) imaging for transthyretin amyloid cardiomyopathy (ATTR-CM). We summarize the advantages of single-photon emission computed tomography (SPECT) over planar imaging, the potential impact of quantitative methods, and emerging data for quantifying response to therapy. The current literature demonstrates the superior diagnostic accuracy of SPECT compared with planar imaging in 99mTc-PYP studies. Emerging quantitative methods, using hybrid SPECT/CT and artificial intelligence, show promise for enhancing diagnostic precision and risk assessment. Recent studies have also highlighted the potential of 99mTc-PYP quantification for monitoring treatment response. 99mTc-PYP SPECT imaging has exceptional diagnostic accuracy for ATTR-CM. Quantitative techniques, which can be facilitated by artificial intelligence, improve risk stratification and may aid in treatment monitoring. Future research should focus on clarifying the clinical role and optimal approach for quantification.

Three-Dimensional Echocardiographic Assessment of Right Ventricular Global Myocardial Work and Ventricular-Pulmonary Coupling in ATTR Cardiac Amyloidosis.

Background: Right ventricular (RV) function is inadequately investigated and routinely overlooked in transthyretin amyloid cardiomyopathy (ATTR-CM). Novel imaging distinguishers between intrinsic RV myocardial disease in ATTR-CM and primary RV overload disorder phenotypes may enhance mechanistic and pathophysiological understanding of RV dysfunction. We aimed to investigate RV performance in ATTR-CM employing comprehensive 2D and 3D echocardiography, and to compare these indices with primary RV afterload disease. Methods: We investigated conventional and novel indices of RV contractile function, myocardial work and ventricular-vascular coupling in 21 well-characterized ATTR-CM patients, 10 PAH patients and 12 healthy controls. RV long axis function and pulmonary artery (PA) systolic pressure were evaluated using 2D Doppler echocardiography. RV ejection fraction (RVEF), volumes, global longitudinal strain (GLS) and novel myocardial work indices were analyzed by 3D echocardiography. RV elastance (Ees), afterload (Ea) and RV-PA coupling (Ees/Ea) were estimated using the single-beat volume method. Results: ATTR-CM showed lower RVEF, GLS and Ees, and a higher RV global myocardial work index (GWI), constructive work (GCW), Ea and reduced RV-PA coupling compared with controls. RV EF, stroke volume, GLS and circumferential strain did not differ between ATTR-CM and PAH. However, GWI, GCW, Ees and Ea were lower in ATTR-CM. RV-pulmonary coupling displayed strong association with RV 3D strain (r = 0.84, p < 0.001), whereas RV Ees (contractility) was related to RV GWI (r = 0.54, p < 0.001). Conclusions: ATTR-CM displayed lower RV performance, higher GMW and reduced RV-PA coupling. Myocardial work indices Ees and Ea are novel distinguishers of RV dysfunction phenotypes. The clinical and prognostic value of these novel variables warrant further investigation.

Usefulness of the Columbia score for predicting outcomes in patients with transthyretin amyloid cardiomyopathy. Analysis of the Galician registry of cardiac amyloidosis

Aims To evaluate the predictive value of the Columbia score in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Methods Observational study based in a prospective, multi-centre registry of patients with ATTR-CM recruited between January–2018 and December–2023 in 7 Spanish hospitals. The Baseline Columbia score was correlated by means of multivariable Cox’s regression with study endpoints all-cause death and all-cause death or heart failure (HF) hospitalisation. Discriminative capacity was evaluated by means of Harrell’s C statistics and area under 2-year time-dependent receiver-operator curves. Results We studied 374 patients with ATTR-CM. Columbia score was independently associated with increased risk of all-cause death (adjusted HR per 1 point = 1.30, 95% CI 1.17–1.45) and all-cause death or HF hospitalisation (adjusted HR per 1 point = 1.38, 95% 1.26–1.50). The score showed moderate discriminative capacity for all-cause death (Harrell’s C = 0.653) and all-cause death or HF hospitalisation (Harrell’s C = 0.697). The area under the 2-year time-dependent receiver-operator curve was 0.594 for all-cause death and 0.669 for all-cause death or HF hospitalisation. Columbia’s score was adequately calibrated for both outcomes. Conclusions We studied the prognostic performance of the Columbia score in a Spanish prospective cohort of patients with ATTR-CM. The score showed adequate calibration and moderate discriminative capacity for predicting death and HF hospitalisations.

Clinical significance of the estimation of pulmonary-right ventricular uncoupling in patients with transthyretin amyloid cardiomyopathy.

There are few data on the prognostic impact of pulmonary-right ventricular (RV) uncoupling in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). Among the 174 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from 2002 to 2021, 143 patients who met the current Japanese guideline and had sufficient information for two-dimensional speckle tracking echocardiography were retrospectively analysed. During a median follow-up of 1209 days, 39 cardiac deaths occurred. Compared with patients in the non-event group, those in the cardiac death group were significantly older (79.3 ± 6.7 vs. 76.4 ± 6.2, respectively; P < 0.05). Additionally, RV global longitudinal strain (RV-GLS)/systolic pulmonary artery pressure (sPAP), an index of pulmonary-RV uncoupling, was significantly lower in patients in the cardiac death group vs. the non-event group [0.29 (0.18-0.35) vs. 0.40 (0.29-0.57), P < 0.01]. Multivariate Cox proportional hazards regression analysis demonstrated that RV-GLS/sPAP was significantly associated with cardiac death after adjusting for tricuspid annular plane systolic excursion/sPAP (P < 0.01), sPAP (P < 0.05), and conventional prognostic factors including age and hospitalization for heart failure (<0.01), laboratory finding including high-sensitivity cardiac troponin T, and B-type natriuretic peptide (P < 0.01). Receiver operating characteristic analysis showed that the area under the curve for RV-GLS/sPAP for cardiac death was 0.72 and that the best cut off value for RV-GLS/sPAP was 0.34 (sensitivity, 76%; specificity, 65%). In the Kaplan-Meier analysis, patients with ATTRwt-CM who had low vs. high RV-GLS/sPAP (cut-off value 0.34) had a significantly higher probability of cardiac death (P < 0.01). Pulmonary-RV uncoupling has significantly higher prognostic value compared with conventional prognostic factors in ATTRwt-CM.

Impact of Tafamidis on [99mTc]Tc-pyrophosphate Scintigraphy in Ala97Ser Hereditary Transthyretin amyloid cardiomyopathy: significant initial reduction with stable Long-Term effects.

Tafamidis has shown potential in slowing disease progression in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This study aimed to evaluate serial changes on [99mTc]Tc-pyrophosphate (PYP) scintigraphy during tafamidis treatment for hereditary ATTR-CM. We retrospectively analyzed a prospectively collected cohort of Ala97Ser (A97S) hereditary ATTR-CM patients treated with tafamidis (61mg/day) and a control group comprising A97S hereditary ATTR-CM patients who had not received disease-modifying medications. The tafamidis group was further divided into two cohorts: cohort A received [99mTc]Tc-PYP SPECT/CT scans at baseline, 1 year, and 2 years; cohort B at baseline, 2 years, and 3 years. Visual score, planar heart to contralateral lung (H/CL) ratio, and volumetric heart to lung (H/L) ratio were measured. Nineteen patients were enrolled in the tafamidis group and nine in the control group. After 2 years of follow-up, a significant decrease in volumetric H/L ratio (3.86 ± 0.91 to 3.01 ± 0.19, p < 0.001) was noted in the tafamidis group, while there was no significant change in the control group. When evaluated over time, a significant decrease in volumetric H/L ratio was observed during the first year of tafamidis treatment (3.75 ± 0.37 to 2.82 ± 0.15, p = 0.004), followed by stable [99mTc]Tc-PYP uptake in the subsequent two years (2.82 ± 0.15 to 2.83 ± 0.18, p = 0.934 and 3.20 ± 0.14 to 3.09 ± 0.16, p = 0.404, respectively). A significant reduction in [99mTc]Tc-PYP uptake was observed in hereditary ATTR-CM patients after tafamidis treatment, particularly within the first year. While the effect appeared to be sustained, stable [99mTc]Tc-PYP uptake without further significant reductions was observed in the subsequent years.

Role of 99mTc-pyrophosphate myocardial scintigraphy in assessing the efficiency of tafamidis therapy: a case series

Introduction. In recent years, the detection rate of transthyretin amyloid cardiomyopathy has been rapidly increasing. The only drug registered as a pathogenetic therapy in Russia is tafamidis. To date, there is no single protocol for assessing disease progression, and the role of scintigraphy with phosphate complexes is not reflected in current documents due to the lack of evidence.Brief description. The article presents a case series including patients who received tafamidis therapy for at least 12 months. During therapy, there were no signs of disease progression, and in some cases, according to myocardial scintigraphy with phosphate complexes, a decrease in radiopharmaceutical uptake was noted.Discussion. The role of myocardial scintigraphy with phosphate complexes for monitoring the effectiveness of tafamidis therapy was discussed.