Cardiac amyloidosis is an infiltrative cardiomyopathy caused by the deposition of insoluble amyloid fibrils in the myocardium, leading to abnormal cardiac function and heart failure. Diagnosis is often challenging due to its diverse symptoms and related comorbidities. Although endomyocardial biopsy is the gold standard for diagnosis, a complete diagnostic approach often includes non-invasive methods such as Cardiac Magnetic Resonance (CMR) and nuclear medicine techniques. Nuclear medicine bone-seeking agents are useful for diagnosing the transthyretin (ATTR) amyloidosis subtype. CMR is especially useful when echocardiography results are inconclusive or for differentiating cardiac amyloidosis from other conditions like hypertrophic cardiomyopathy. CMR provides a comprehensive evaluation of morphological and functional abnormalities, inversion time, late gadolinium enhancement, and can include advanced techniques such as T1 mapping and extracellular volume quantification for diagnostic and prognostic purposes. This review outlines how CMR and nuclear medicine are integral to the diagnostic process for cardiac amyloidosis, emphasizing their crucial roles and the synergy between various diagnostic techniques in assessing suspected cases. ESSENTIALS: REQUIRED SUMMARY STATEMENT: Nuclear medicine PYP scans and CMR play a pivotal role in the non-invasive diagnosis of cardiac amyloidosis, alongside other essential diagnostic modalities.

99mTechnetium-pyrophosphate ([99mTc]Tc-PYP) scintigraphy is the gold standard for diagnosing transthyretin amyloid cardiomyopathy (ATTR-CM). Conventional metrics, such as heart-to-contralateral-chest (H/CL) ratio and visual Perugini score, can be influenced by physiological blood pool uptake, leading to false positives and additional patient burdens. This study aimed to develop and validate a simple quantitative metric widely applicable for ATTR-CM diagnosis.

This multicenter retrospective study enrolled 253 patients who underwent [99mTc]Tc-PYP SPECT/CT between April 2021 and September 2024. SPECT/CTs were acquired 3 h post-injection of 740 MBq [99mTc]Tc-PYP. A lateral wall-to-aorta (LW/Ao) ratio was obtained by dividing the average radiotracer count in the lateral wall of the left ventricle by the average count in the ascending aorta. The diagnosis of ATTR-CM diagnosis was determined by endomyocardial biopsy. As statistical analyses, area under receiver operating characteristic (AUC) was used to compare diagnostic accuracy, and intraclass correlation coefficient (ICC) was used to assess inter-rater agreement.

Among 52 patients (31 men; mean age 77) whose biopsy results were available, 11 were diagnosed with ATTR-CM. LW/Ao ratio showed a sensitivity of 100% (11/11), specificity of 97.6% (40/41), and positive likelihood ratio of 41.0. LW/Ao ratio showed higher AUC (0.99; 95% CI: 0.99-1.00) compared to H/CL ratio (AUC = 0.90, p = 0.04) and visual score (AUC = 0.87, p < 0.01). The ICC of LW/Ao ratio was excellent (0.91 ≥ 0.9).

The quantitative SPECT/CT metric demonstrated superior diagnostic accuracy for ATTR-CM compared to conventional methods.

Transthyretin cardiac amyloidosis is an increasingly recognized infiltrative cardiomyopathy that is implicated in a growing number of cases of heart failure. Although it was once considered a disease without a cure, there have been rapid advances in pharmacotherapy over recent decades. The agents currently approved by the United States Food and Drug Administration-tafamidis and acoramidis-are transthyretin stabilizers that prevent the breakdown of the physiologic transthyretin tetramer into fibril-forming monomers. While these agents help prevent disease progression, they do not reverse existing disease. ALXN2220 (previously called NI006) addresses this unmet need. A recombinant human IgG1 monoclonal antibody with high specificity for transthyretin monomers and amyloid fibrils, ALXN2220 stimulates macrophage-mediated phagocytosis of deposited amyloid fibrils. Phase 1 studies have demonstrated the tolerability of doses ranging from 0.3 to 60 mg/kg/month. At doses higher than 10 mg/kg/month, ALXN2220 has demonstrated the ability to decrease cardiac tracer uptake on scintigraphy and decrease the extracellular volume on cardiac magnetic resonance imaging at 4 and 12 months when compared with placebo. These imaging parameters are known surrogates for the burden of cardiac amyloid deposition. In addition, significant reductions in levels of n-terminal proBNP and troponin T, as well as improvements in Kansas City Cardiomyopathy Questionnaire scores were also noted. The adverse effect and immunogenicity profiles were encouraging as well. A multinational, placebo-controlled phase 3 trial (DepleTTR-CM) is ongoing to assess long-term efficacy, functional outcomes, and survival impact. These results are expected to provide critical real-world evidence on ALXN2220's role in transthyretin cardiac amyloidosis management.

Nuclear medicine scintigraphy using 99mTc-pyrophosphate has proven valuable in the diagnosis of cardiac transthyretin amyloidosis in recent years. However, there is still confusion over the optimal imaging time points. The American Society of Nuclear Cardiology has recommended different imaging time points over the last decade. We aimed to determine whether single- or dual-time-point imaging is required for reporting purposes and which time point would be the most appropriate if a single time point was to be considered. Methods: Cardiac amyloid scans using 99mTc-pyrophosphate acquired from 2017 to 2023 were retrieved from our Picture Archiving and Communications System. Scans with static views and SPECT/CT images of the chest for both imaging time points, at 1 h (early) and 3 h (delayed) after injection, were included. Each study was independently read by 3 nuclear medicine physicians. Original clinical reports using both imaging time points were used as a reference to calculate the accuracy of a single time point. Results: In total, 70 patients were included in this study. Reports of cardiac amyloid studies using any single-time-point imaging were highly sensitive, accurate, and specific. There was agreement among all readers. Of the 140 datasets reported by each reader, 4 scans were classified as equivocal, requiring more imaging for confident reporting. Conclusion: Single-time-point imaging showed an accuracy comparable to the dual-time-point imaging in diagnosing cardiac transthyretin amyloidosis. This was further validated by agreement among the 3 readers. Early time-point imaging is preferred, and additional delayed imaging can be acquired when the early result is equivocal.

Artificial intelligence is poised to transform cardio-oncology by enabling personalized care for patients with cancer, who are at a heightened risk of cardiovascular disease due to both the disease and its treatments. The rising prevalence of cancer and the availability of multiple new therapeutic options has resulted in improved survival among patients with cancer and has expanded the scope of cardio-oncology to not only short-term but also long-term cardiovascular risks resulting from both cancer and its treatments. However, there is considerable heterogeneity in cardiovascular risk, driven by the nature of the malignancy as well as each individual's unique characteristics. The use of novel therapies, such as targeted therapies and immune checkpoint inhibitors, across multiple cancer groups has also broadened the populations among which cardiotoxicity has become an important consideration of therapy. Therefore, the ability to understand and personalize cardiovascular risk management in patients with cancer is a key target for artificial intelligence, which can deduce and respond to complex patterns within the data. These advances necessitate an overview of established biomarkers of risk, spanning advanced imaging, diagnostic testing, and multi-omics, the evidence supporting their use, and the proven and proposed role of artificial intelligence in refining this risk to attain greater precision in risk prediction and management in cardio-oncologic care.

Cardiac amyloidosis represents a unique disease process characterized by amyloid fibril deposition within the myocardial extracellular space. Advances in multimodality cardiac imaging enable accurate diagnosis and facilitate prompt initiation of disease-modifying therapies. Furthermore, rapid advances in multimodality imaging have enriched understanding of the underlying pathogenesis, enhanced prognostication, and resulted in the development of imaging-based markers that reflect the amyloid burden, which is of increasing importance when assessing the response to treatment. Whereas conventional therapies have focused on reducing amyloid formation and subsequent stabilization of the cardiac disease process, novel agents are being developed to accelerate the immune-mediated removal of amyloid fibrils from the heart. In this context, the ability to track changes in the amyloid burden over time is of paramount importance. Although advanced imaging techniques have shown efficacy in tracking the treatment response, future research focused on improved precision through use of artificial intelligence may augment the detection of changes earlier in the course of treatment.

Amyloidosis is an infiltrative disease that may cause cardiomyopathy if the precursor protein that misfolds and forms the amyloid is transthyretic or plasma abnormal light chains. Transthyretin amyloid cardiomyopathy has to be diagnosed timely and accurately since there are specific treatment options to support the patients. Multimodality imaging including electrocardiography, echocardiography with strain imaging and cardiac magnetic resonance applying late gadolinium enhancement imaging, native T1 mapping and extracellular volume, raise a high suspicion of the disease and bone scintigraphy set the diagnosis even without the need of biopsy. However, the morbidity and mortality remain high and the need for risk stratification and assessment of the response to treatment are of paramount importance. Cardiac imaging biomarkers offer a thoughtful insight into the prognosis of these patients at diagnosis and after treatment. The current narrative review aims to enlighten the use of multimodality cardiac imaging in transthyretic amyloid cardiomyopathy throughout the disease pathogenesis and evolution from diagnosis to prognosis and response to treatment in a personalized manner.

Hereditary transthyretin amyloidosis (ATTRv) is an autosomal dominant genetic disease characterized by the misfolding and deposition of the transthyretin (TTR) protein. This study aimed to describe the clinical and genetic characteristics of ATTRv in a large multicenter Chinese cohort.

Patients from 14 centers were included in the study. The clinical and genetic characteristics of all patients were summarized. The peripheral blood white blood cell mitochondrial DNA (mtDNA) was detected in offspring from different genders.

A total of 202 individuals with ATTRv from 148 families were identified. The average age of onset was 50.6 ± 12.4 years. Among these cases, 117 (57.9%) were classified as late-onset (≥50 years) and 85 (42.1%) as early-onset. Overall, the length dependent axonal sensorimotor peripheral neuropathy was the predominant phenotype (89.1%). A total of 42 heterozygous missense variants and 1 deletion variant were identified. The most common variants were Val30Met (19.8%) and Ala97Ser (15.8%) and patients with Val30Met and Ala97Ser were mostly late-onset in our cohort. Thirty-nine of these patients died with a mean age of 56.1 ± 13.5 years. Anticipation according to gender groups of offspring-parent pairs was different, and mother-son pairs showed the largest anticipation. The copies of mtDNA in the mother's offspring outnumbered those of the father's offspring (p < 0.001).

This study highlights that ATTRv patients in China exhibit high heterogeneity in their initial symptoms. The most common variants observed in this cohort is Val30Met. The mtDNA copy number shows gender-linked effects. These results can impact ATTRv diagnosis and patient care strategies. ANN NEUROL 2025.

Cardiac amyloidosis (CA), predominantly caused by amyloid transthyretin (ATTR) or immunoglobulin light chain (AL), has a poor prognosis, and a precise diagnosis is crucial because the optimal treatments differ between the two conditions. However, diagnosing AL-CA is challenging because of the unavailability of effective AL-detecting antibodies, particularly in cases with coexisting AL- and ATTR-CA. This report presents a successfully diagnosed case of complicated AL- and ATTR-CA that was successfully treated with tafamidis for ATTR-CA and combination chemotherapy for AL-CA. This case highlights the importance of a precise diagnosis of CA and supports the efficacy and safety of concurrent treatment for coexisting amyloidosis.

The 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.

This 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).

Tafamidis 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).

Tafamidis 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.

Transthyretin amyloidosis (ATTR) is a rare disease that results in amyloid fibril misfolding and deposition in multiple organs, including the heart, leading to the development of ATTR cardiomyopathy (ATTR-CM), which is associated with poor outcomes. In the last decade, several disease-modifying medications are in advanced stages of clinical development or have been approved to treat ATTR-CM. The purpose of this review is to critically evaluate clinical trial data investigating the use of approved and investigational medications for the treatment of ATTR-CM. We performed a comprehensive literature search via PubMed and EMBASE to identify randomized controlled trials evaluating medications for the treatment of ATTR-CM published through August 2024. This narrative review describes the pathophysiology of ATTR-CM, highlights important screening and diagnostic work-up, and summarizes the existing clinical evidence resulting from our literature search. Several classes of disease-modifying medications are in development for ATTR-CM. The tetramer stabilizers and transthyretin silencers have proven to be the most effective therapies to date. Tafamidis and acoramidis are currently approved for ATTR-CM while vutrisiran approval for ATTR-CM may be forthcoming. Other disease-modifying medication classes in development include antisense oligonucleotides, gene editing therapies, and monoclonal antibodies. However, several unmet needs exist including the lack of cost-effectiveness due to the extremely high acquisition costs of these medications. Disease-modifying medications approved and in development to treat ATTR-CM offer hope for patients with this disease, but their lack of affordability is the biggest barrier to their use.

Transthyretin cardiac amyloidosis (ATTR-CA) involves the buildup of transthyretin protein in the heart muscle in the form of amyloid fibrils, which can affect heart structure and function. Common ECG findings of ATTR-CA include low QRS voltage and a pseudo-myocardial infarction (MI) pattern, defined as pathological Q waves or QS complexes in two consecutive leads without a history of MI or echocardiographic evidence of akinetic areas. Here, we present a case of ATTR-CA in a very elderly patient, in whom pathological Q waves on ECG were true indicators of a prior inferior MI. A 96-year-old woman with a history of inferior MI presented to her primary care clinic with a one-week history of nocturnal dyspnea. She had undergone coronary stent placement in the distal right coronary artery five years earlier for inferior MI. An ECG revealed abnormal Q waves, ST elevation of 0.5 mm, and T wave inversion in limb leads III and aVF, with no significant findings suggestive of left ventricular (LV) hypertrophy. Over a two-year period, QRS voltage progressively decreased in all leads, while the ST-T changes remained unchanged. Transthoracic echocardiogram (TTE) showed LV concentric hypertrophy with an increased wall thickness of 14 mm, except in the infero-septal region. In basal and mid-short-axis views, infero-septal wall motion was severely reduced, with notable wall thinning in contrast to the global LV hypertrophy observed elsewhere - findings consistent with prior inferior MI. The patient was ultimately diagnosed with ATTR-CA based on technetium-99m-pyrophosphate scintigraphy and monoclonal protein detection tests. Clinicians should recognize that pathological Q waves in ATTR-CA do not always indicate a pseudo-MI pattern. When both ECG and TTE suggest an MI pattern, further evaluation for coronary artery disease is warranted as part of the ATTR-CA diagnostic workup. In patients with both ATTR-CA and prior MI, a comprehensive clinical approach addressing both conditions is essential for optimizing prognosis.

In the last decade, we have witnessed dramatic improvements in the diagnosis, workup, management, and monitoring of patients with hereditary transthyretin amyloidosis (ATTRv). Updated imaging techniques (e.g., 99mTc-PYP scan) are increasingly being used in place of tissue biopsies for confirmation of disease. Novel treatments now include antisense oligonucleotide and RNA interference drugs, whereas new applications such as CRISPR and amyloid antibodies are being studied for potential use in the future. These treatments have dramatically improved quality of life and increased survival in patients with ATTRv. Despite these breakthroughs, many challenges remain. Some of these challenges include early recognition and diagnosis of ATTRv, monitoring and initiation of treatment in asymptomatic or paucisymptomatic carriers, adequate treatment in people with mixed phenotype (i.e., cardiac and neurological), and the emergence of new phenotypes in people living longer with the disease (i.e., central nervous system and ocular complications). Research in those areas of deficit is ongoing, and in the future, we may have preventive therapies, better biomarkers, more efficient therapies for organs that we cannot currently target, and enhanced diagnostic techniques with the help of novel imaging techniques and artificial intelligence. In this review, we will summarize the current knowledge about polyneuropathy related to ATTRv and its management, discuss methods to improve early diagnosis and monitoring, and discuss emerging trends.

To evaluate right ventricular (RV) uptake measured by quantitative [99mTc]Tc-DPD SPECT/CT to investigate its role in predicting and evaluating prognosis and therapeutic outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CA).

Patients with ATTR-CA were consecutively enrolled for quantitative [99mTc]Tc-DPD SPECT/CT. Ventricular amyloid burden was quantified by SUVmax and TBR. Differences in RV uptake (focal or diffuse) and associations with clinical characteristics and CMR data were evaluated. The primary endpoint was major adverse cardiac events (MACEs), including all-cause deaths, heart failure hospitalizations, complete atrioventricular block, sustained ventricular tachycardia, and atrial fibrillation/flutter. Prognostic associations were evaluated using Cox regression and Kaplan-Meier survival analysis. A secondary endpoint involved a longitudinal SPECT/CT analysis during Tafamidis therapy.

The study included 76 patients, all showing both RV and LV uptake on SPECT imaging. Compared with patients with focal RV uptake, patients with diffuse RV uptake had higher serum troponin T levels (P < 0.05), septal thickness (P < 0.01), and external cardiac circulation volume (ECV) (P < 0.05). RV uptake was correlated with septal thickness, ECV, LV uptake, NT-proBNP and troponin-T (all P < 0.05). Among 53 patients, high LV and RV uptake significantly predicted MACEs (P < 0.001), with a median follow-up time of 16 months. A subgroup of 20 patients showed significant reductions in LV and RV uptake after Tafamidis treatment (P < 0.001).

Increasing RV amyloid burden quantified by SPECT/CT is associated with advanced disease stage and predicts MACEs, serving as valuable markers for prognosis and treatment monitoring in ATTR-CA.

Quantification of cardiac [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake enhances diagnostic capabilities and may facilitate prognostic stratification in patients with transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to evaluate the association of quantitative left ventricular (LV) DPD uptake with myocardial structure and function, and their implications on outcome in ATTR-CA.

Consecutive ATTR-CA patients (n = 100) undergoing planar DPD scintigraphy with Perugini grade 2 or 3, alongside quantitative DPD single-photon emission computed tomography/computed tomography imaging and speckle-tracking echocardiography between 2019 and 2023, were included and divided into two cohorts based on median DPD retention index (low DPD uptake: ≤5.4, n = 50; high DPD uptake: >5.4, n = 50). The DPD retention index showed significant, albeit weak to modest, correlations with LV global longitudinal strain (LV-GLS: r = 0.366, P < 0.001), right ventricular free wall longitudinal strain (RV-FW-LS: r = 0.316, P = 0.002), LV diastolic function (E/e' average: r = 0.304, P = 0.013), NT-proBNP (r = 0.332, P < 0.001), troponin T (r = 0.233, P = 0.022), 6 min walk distance (6MWD: r = -0.222, P = 0.033), and National Amyloidosis Centre (NAC) stage (r = 0.294, P = 0.003). ATTR-CA patients in the high DPD uptake cohort demonstrated more advanced disease severity regarding longitudinal cardiac function (LV-GLS: P = 0.012, RV-FW-LS: P = 0.036), LV diastolic function (E/e' average: P = 0.035), cardiac biomarkers (NT-proBNP: P = 0.012, troponin T: P = 0.044), exercise capacity (6MWD: P = 0.035), and disease stage (NAC stage I: P = 0.045, III: P = 0.006), and experienced adverse outcomes compared with the low DPD uptake cohort [composite endpoint: all-cause death or heart failure hospitalization, HR: 2.873 (95% CI: 1.439-5.737), P = 0.003; DPD retention index: adjusted HR 1.221 (95% CI: 1.078-1.383), P = 0.002].

In ATTR-CA, enhanced quantitative LV DPD uptake indicates advanced disease severity and is associated with adverse outcome. DPD quantification may facilitate prognostic stratification when diagnosing patients with ATTR-CA.

This study aimed to evaluate the diagnostic performance of 99m Tc-hydroxymethylene diphosphonate ( 99m Tc-HMDP) imaging for cardiac amyloidosis and to demonstrate changes in cardiac uptake of 99m Tc-HMDP after tafamidis treatment.

Seventy-five patients with suspected cardiac amyloidosis who underwent 99m Tc-HMDP imaging were included. We compared visual Perugini grades and semiquantitative heart-to-contralateral (H/CL) area ratios, myocardial maximum standardized uptake value (SUVmax), and peak of SUV (SUVpeak) between cardiac transthyretin amyloidosis (ATTR) and amyloid light-chain amyloidosis (AL). Comparison of interobserver reproducibility between H/CL ratios and myocardial SUVmax/SUVpeak was performed. H/CL ratio of 99m Tc-HMDP and myocardial SUVmax/SUVpeak were compared before and after tafamidis administration for cardiac wild-type ATTR.

Among 75 patients, 20 patients (26.7%) were visually positive based on Perugini grade. Fifteen and three patients were pathologically identified as cardiac ATTR and AL, respectively. ATTR group ( n  = 15) had significantly higher H/CL ratios of 99m Tc-HMDP than AL group ( n  = 3) ( P  = 0.003). ATTR group ( n  = 15) had significantly higher myocardial SUVmax/SUVpeak of 99m Tc-HMDP than AL group ( n  = 2) ( P  = 0.015). Myocardial SUVmax/SUVpeak had better interobserver reproducibility than H/CL ratios. After tafamidis treatment for cardiac wild-type ATTR, the decrease in myocardial SUVpeak was significant but not in H/CL ratios and myocardial SUVmax.

H/CL ratio and SUVmax/SUVpeak in 99m Tc-HMDP imaging were useful for diagnosing cardiac ATTR. Myocardial SUVpeak may be useful for monitoring changes in cardiac uptake after tafamidis treatment for cardiac ATTR.

The prevalence of wild-type transthyretin (ATTR) amyloidosis is increasing with advancements in diagnostic techniques and growing awareness of the disease worldwide. 99mTc-labeled pyrophosphate (99mTc-PYP) scintigraphy exhibits high performance in diagnosing ATTR cardiac amyloidosis. This study aimed to validate the characteristics of patients with positive 99mTc-PYP scintigraphy results in a multicenter setting to provide more accurate case selection criteria.

In total, 180 patients with suspected ATTR amyloidosis underwent 99mTc-PYP scintigraphy in participating institutions in Japan between January 2018 and July 2022. Of 135 patients included in the analysis, 62 were 99mTc-PYP-positive. Logistic regression analysis was performed, and the following five factors were adopted to create a scoring system, with each weighted according to its odds ratio value; 1 point was scored for the absence of hypertension, existence of peripheral entrapment neuropathy (carpal tunnel syndrome or spinal canal stenosis), conduction disturbance (the presence of QRS complex ≥120 ms, first-degree atrioventricular block, higher degree of atrioventricular block, or presence of pacemaker implantation), and left ventricular hypertrophy and 2 points for troponin I/T ≥ 0.06 ng/mL. 99mTc-PYP scintigraphy positivity rate in the 0-point group was 0 %, whereas that in the 6-point group was 100 %. The area under the curve of the criteria was 0.820 (95 % confidence interval, 0.752-0.888; P < 0.001).

The combination of clinical information, which is easily available in local clinics, can provide accurate pretest prediction of positive 99mTc-PYP scintigraphy results. This will help clinicians to make an early diagnosis of ATTR amyloidosis.

The prognostic value of bone scintigraphy in cardiac amyloidosis (CA) remains undetermined. We conducted a systematic review and meta-analysis on the association of cardiac uptake on bone scintigraphy with mortality in known or suspected CA.

PubMed, Embase, and Cochrane library databases were searched up to November 2023 for studies that evaluated cardiac uptake on bone scintigraphy as a prognostic factor in the workup of CA. Hazards ratios (HRs) of high cardiac uptake for outcomes of all-cause or cardiac death were pooled and analyzed with stratifications according to the study populations, analytical methodologies, and radiotracers.

Fourteen studies (3325 patients) were finally included. In studies regarding known or suspected CA, visual grades were not prognostically significant, regardless of the threshold used, with pooled HRs of 2.25 (95% confidence interval [CI], 0.93-5.48), 1.55 (95% CI, 0.89-2.68), and 1.53 (95% CI, 0.95-2.47) for visual grades ≥1, ≥2, and ≥3, respectively. By contrast, high cardiac uptake on semiquantitative measurements (heart-to-contralateral lung ratio, n = 6; heart-to-whole-body ratio, n = 1) was associated with increased mortality (pooled HR = 2.27 [95% CI, 1.87-2.76] for all semiquantitative measurements; 2.26 [1.86-2.74] for heart-to-contralateral lung ratio only). No difference in prognostic significance was found across 3 different 99m Tc-radiotracers ( P = 0.619). However, high cardiac uptake was not predictive of mortality in aortic stenosis-related CA (pooled HR = 1.13 [95% CI, 0.96-1.32]).

High semiquantitative cardiac uptake on bone scintigraphy is associated with an increased risk of mortality in patients with known or suspected CA.

Quantifying myocardial extracellular volume (ECV) using computed tomography (CT) has been shown to be useful in the evaluation of cardiac amyloidosis. However, the reproducibility of CT measurements for myocardial ECV, is not well-established in patients with proven cardiac amyloidosis.

This prospective single-center study enrolled cardiac amyloidosis patients to undergo dual-energy CT for myocardial fibrosis assessment. Delayed imaging at 7 and 8 ​min post-contrast and independent evaluations by two blinded cardiologists were performed for ECV quantification using 16-segment (ECVglobal) and septal sampling (ECVseptal). Inter- and intraobserver variability and test-retest reliability were measured using Spearman's rank correlation, Bland-Altman analysis, and intraclass correlation coefficients (ICC).

Among the 24 participants (median age ​= ​78, 67 ​% male), CT ECVglobal and ECVseptal showed median values of 53.6 ​% and 49.1 ​% at 7 ​min, and 53.3 ​% and 50.1 ​% at 8 ​min, respectively. Inter- and intraobserver variability and test-retest reliability for CT ECVglobal (ICC ​= ​0.798, 0.912, and 0.894, respectively) and ECVseptal (ICC ​= ​0.791, 0.898, and 0.852, respectively) indicated good reproducibility, with no evidence of systemic bias between observers or scans.

Dual-energy CT-derived ECV measurements demonstrated good reproducibility in patients with proven cardiac amyloidosis, suggesting potential utility as a repeatable imaging biomarker for this disease.

Although the relative apical sparing (RAPS) pattern of left ventricular (LV) longitudinal strain is a hallmark of cardiac amyloidosis, recent studies have raised concerns about its accuracy. The aim of this systematic review was to investigate diagnostic test accuracy (DTA) and prognostic impact of RAPS in cardiac amyloidosis.

We searched PubMed, Embase, and Scopus for manuscripts that could potentially be used in the DTA arm and prognosis arm. Thirty-seven studies were used for DTA analysis. The pooled sensitivity, specificity, and diagnostic odds ratio were 61% (95% confidence interval [CI] 54-68%), 83% (95% CI 80-86%), and 8.9 (95% CI 6.1-13.1), respectively. These values did not differ regardless of the presence of aortic stenosis, but the diagnostic odds ratio differed significantly among analytical software packages. For the prognosis arm, 6 studies were dichotomously assessed for RAPS, and 5 were assessed quantitatively. The pooled proportion of RAPS was 49% and the pooled estimate of the RAPS ratio was 1.40. Although RAPS was associated with outcome (hazard ratio [HR] 1.87; 95% CI 1.15-3.04; P=0.011), its significance disappeared after trim and fill analysis (HR 1.42; 95% CI 0.85-2.38; P=0.184).

RAPS has a modest DTA with a significant vendor dependency and does not provide robust prognostic information.

Exercise capacity is related to mortality and morbidity in heart failure (HF) patients. Determinants of exercise capacity in transthyretin cardiac amyloidosis (ATTR-CA) have not been established.

This single-center study retrospectively evaluated ATTR-CA patients and patients with non-amyloidosis HF with preserved/mildly reduced ejection fraction (HFpEF/HFmrEF) (n=32 and n=51, respectively). In the ATTR-CA group, the median age was 75.5 years (interquartile range [IQR] 71.3-78.8 years), 90.6% were male, and the median left ventricular (LV) ejection fraction was 53.5% (IQR 41.4-65.6%). Cardiopulmonary exercise tests revealed a median peak oxygen consumption and anaerobic threshold of 15.9 (IQR 11.6-17.4) and 10.6 (IQR 8.5-12.0] mL/min/kg, respectively, and ventilatory efficiency (minute ventilation/carbon dioxide production [V̇E/V̇CO2] slope) of 35.5 (IQR 32.0-42.5). Among exercise variables, V̇E/V̇CO2slope has the greatest prognostic value. Univariate analysis revealed a significant correlation between V̇E/V̇CO2slope and age, LV global longitudinal strain, tricuspid annular plain systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) ratio, and mixed venous oxygen saturation. In multivariate analyses, the TAPSE/PASP ratio was an independent predictor of V̇E/V̇CO2slope (95% confidence interval -44.5, -10.8; P=0.0067). In non-amyloidosis HFpEF/HFmrEF patients, the TAPSE/PASP ratio was not independently correlated with V̇E/V̇CO2slope.

Right ventricular-pulmonary artery coupling estimated by the TAPSE/PASP ratio determines exercise capacity in ATTR-CA patients. This highlights the importance of early therapeutic intervention against underappreciated right ventricular dysfunction associated with ATTR-CA.

High-sensitivity cardiac troponin T (hs-cTnT) was proposed as a simple and useful diagnostic tool for cardiac amyloidosis (CA). We performed exploratory systemic screening using hs-cTnT to detect wild-type transthyretin CA (ATTRwt-CA) in outpatient and community-based settings.

This study was a prospective multicenter study including 8 internal medicine clinics in Kochi Prefecture, Japan. Consecutive individuals aged ≥70 years who visited those clinics as outpatients were enrolled. Patients with a prior diagnosis of CA or a history of heart failure hospitalization were excluded. We measured hs-cTnT levels in the enrolled individuals at each clinic, and those with elevated hs-cTnT levels (≥0.03ng/mL) received further detailed examination, including remeasurement of hs-cTnT. The diagnosis of ATTRwt-CA was confirmed by biopsy-proven transthyretin. Of 1,141 individuals enrolled in the study, 55 (4.8%) had elevated hs-cTnT levels. Of the 33 patients who underwent further examination, 22 had elevated hs-cTnT levels at remeasurement. Finally, 2 men were diagnosed with ATTRwt-CA. The prevalence of ATTRwt-CA was 9.1% (2/22) among patients with elevated hs-cTnT levels at two examinations, and at least 0.18% (2/1,141) in the whole study population.

Measurement of hs-cTnT will help to screen for patients with undiagnosed ATTRwt-CA in primary care practice.

Cardiac amyloidosis (CA) is an underdiagnosed, progressive and lethal disease. Machine learning applied to common measurements derived from routine echocardiogram studies can inform suspicion of CA.

Our objectives were to test a random forest (RF) model in detecting CA.

We used 3603 echocardiogram studies from 636 patients at Cedars-Sinai Medical Center to train an RF model to predict CA from echocardiographic parameters. 231 patients with CA were compared with 405 control patients with negative pyrophosphate scans or clinical diagnosis of hypertrophic cardiomyopathy. 19 common echocardiographic measurements from echocardiogram reports were used as input into the RF model. Data was split by patient into a training data set of 2882 studies from 486 patients and a test data set of 721 studies from 150 patients. The performance of the model was evaluated by area under the receiver operative curve (AUC), sensitivity, specificity and positive predictive value (PPV) on the test data set.

The RF model identified CA with an AUC of 0.84, sensitivity of 0.82, specificity of 0.73 and PPV of 0.76. Some echocardiographic measurements had high missingness, suggesting gaps in measurement in routine clinical practice. Features that were large contributors to the model included mitral A-wave velocity, global longitudinal strain (GLS), left ventricle posterior wall diameter end diastolic (LVPWd) and left atrial area.

Machine learning on echocardiographic parameters can detect patients with CA with accuracy. Our model identified several features that were major contributors towards identifying CA including GLS, mitral A peak velocity and LVPWd. Further study is needed to evaluate its external validity and application in clinical settings.

Transthyretin cardiac amyloidosis (ATTRCA) is a prevalent disease, and it can be associated with heart failure (HF), left ventricle hypertrophy (LVH), atrial fibrillation (AF), and aortic stenosis (AS).

The study aims to detect the prevalence of ATTRCA in the symptomatic AS population.

A single-center prospective study screening for ATTRCA in patients diagnosed with symptomatic severe AS undergoing aortic valve (AV) intervention.

A total of 27 patients were enrolled, of which 15 (56%) were men. The mean age was 72.8 ± 10.5 years. HF symptoms were present in 11 (40.7%) patients at New York Heart Association (NYHA) class II, while 15 (55.6%) patients had NYHA class III symptoms. AF was present in 6 (22.2%) patients. The mean left ventricle ejection fraction (LVEF) was 49.4 ± 9.75%, and the mean stroke volume (SV) was 37.4 ± 8.7 ml/m2. The interventricular septal thickness (IVS) was 1.2 ± 0.18 cm. The AS mean gradient was 46 ± 12 mmHg, and the aortic valve area (AVA) was 0.69 ± 0.16 cm2. The ATTRCA was diagnosed by bone scintigraphy in 5 (18.5%) AS patients. Perugini scores of 2 and 3 were considered positive for ATTRCA with the heart/contralateral lung (H/CL) ratio of 1.48 ± 0.35. There was no difference in LVEF between patients with ATTRCA and those without ATTRCA 50 ± 9.8% vs 47 ± 9.3%; p-value 0.55. The ATTRCA had a lower SV of 33.9 ± 6.9 ml/m2 compared to patients without ATTRCA 37.5 ± 8.8 ml/m2; p-value of 0.34. There was no significant difference in LVH or IVS thickness between the patients with ATTRCA and those without ATTRCA. The left ventricle (LV) mass index in ATTRCA was 87 ± 21 g/m2 compared to patients without ATTRCA 98.7 ± 26 g/m2, with a p-value 0.38, and the IVS thickness was 1.1 ± 0.22 cm compared to patients without ATTRCA 1.2 ± 0.18 cm; p-value 0.17. The left atrial (LA) volumes were significantly higher in the ATTRCA group 55.5 ± 25.6 ml/m2 compared to patients without ATTRCA 37.5 ± 10.9 ml/m2 with a significant p-value 0.028. The mean AV gradient was lower in ATTRCA patients at 40.8 ± 8.4 mmHg, compared to patients without ATTRCA at 46.1 ± 12.1 mmHg; it did not reach a statistical significance p-value 0.3. There was a significant difference in LV relative longitudinal strain (LS) between patients with ATTRCA 11.8 ± 3.2 and those without ATTRCA 63.3 ± 22.6 with a significant p-value 0.001.

ATTRCA is prevalent in AS patients; bone scintigraphy is recommended for screening AS patients for ATTRCA.

Bone scintigraphy is key to non-invasively diagnosing wild-type transthyretin (ATTRwt) amyloidosis, and is mainly used to assess cardiac radiotracer uptake. However, extracardiac radiotracer uptake is also observed. We investigated whether intensity of soft tissue radiotracer uptake is associated with amyloid load in subcutaneous abdominal fat tissue and with mortality.

This prospective cohort study included 94 ATTRwt amyloidosis patients and 26 amyloid-negative heart failure controls who underwent whole-body [99mTc]Tc-hydroxydiphosphonate scintigraphy. Site-to-background ratios were calculated for heart, elbows, subcutaneous tissue, shoulders and wrists on anterior planar bone scintigraphy images using rib and whole-body radiotracer uptake as background. Fat tissue aspirates were stained with Congo red to grade amyloid load. Site-to-rib ratios were compared between ATTRwt amyloidosis patients and controls, and associations of site-to-background ratio with Congo red score and all-cause mortality were studied.

ATTRwt amyloidosis patients had higher soft tissue-to-rib, heart-to-rib and heart-to-whole body ratios compared with controls. The intensity of soft tissue uptake was positively associated with amyloid load in fat tissue in ATTRwt amyloidosis patients. Estimated glomerular filtration rate, N-terminal brain natriuretic propeptide, high-sensitivity cardiac troponin T (hs-cTnT), and the prognostic Mayo and NAC staging system were associated with all-cause mortality in univariable models. Soft tissue/rib ratio, hs-cTnT and the prognostic staging systems were the only two variables that were independently associated withall-cause mortality.

Soft tissue radiotracer uptake on bone scintigraphy in ATTRwt amyloidosis patients is positively associated with amyloid load in abdominal fat tissue and is independently associated with mortality.

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.

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).

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.

Amyloids consist of fibrils that can be formed by a large variety of different precursor proteins. In localized amyloidosis, amyloids accumulate at the production site with a single organ being affected, whereas in systemic amyloidosis several organs are affected, with the heart being the most common, followed by the kidneys, liver, and the nervous system. The two most frequent systemic amyloidosis types affecting the heart in the vast majority (>95%) of cases are immunoglobulin light chain (AL) amyloidosis and transthyretin (TTR) amyloidosis (ATTR amyloidosis). Patients with amyloid cardiopathy (CA) often present with non-specific heart failure symptoms as well as other clinical manifestations depending on the organ or systems involved. However, there are some findings associated with amyloidosis called "red flags" (clinical, echocardiographic, magnetic resonance imaging), which may assist in guiding the physician to the correct diagnosis. The present state-of-the-art review summarizes the features of the various cardiac phenotypic expressions of amyloidosis, proposes a simplified pathway for its diagnosis, and highlights the rapidly evolving therapeutic landscape.

Purpose: We aimed to clarify the clinical characteristics of global and regional myocardial perfusion in patients with transthyretin type of cardiac amyloidosis (ATTR) using dual single-photon emission computed tomography (SPECT) with 99mTc pyrophosphate (PYP) and 201TL (TL). Methods: Consecutive 178 (mean age 78±12, male 79) patients known or suspect of ATTR who underwent PYP-TL dual SPECT were retrospectively enrolled. Patients were categorized according to the visual grading for planar PYP uptake using Perugini grading, and the patients with grade greater than or equal to 2 were analyzed. In planar analysis, the heart/contralateral ratio (H/CL) for PYP, and heart/lung ratio (H/L) for TL were obtained to evaluate global myocardial uptake. In TL-SPECT polar map analysis, the heterogeneity of myocardial uptake was evaluated using segmental mean %uptake. Cardiac function and left ventricular function and end-diastolic ventricular mass (LVmass) were measured by echocardiography. Results: Among 178 patients, 39 patients showed PYP uptake with grade 2 or 3 and H/CL >1.3 (81±5 ys, male 28). Of those, 4 patients showed significant perfusion defect in TL scan. Among 35 patients without perfusion defect, H/L showed a significant inverse correlation to H/CL, and LVmass (r=-0.3, p=0.02; r=-0.4, p=0.03. 95% confidence interval -0.4 to 0.2, and -0.7 to -0.04 for H/CL and LVmass). Polar map analysis demonstrated significantly lower mean %uptake for TL in septum compared to lateral (79.4±8.4 vs. 84.3±6.2, p=0.006 for TL in septum vs. lateral, respectively). Conclusion: In ATTR, TL uptake surrogated the reduction of global myocardial perfusion. A significant regional heterogeneity was observed with a notable reduction in septum despite the diffuse hypertrophy.

Background: This study investigated the feasibility of using a quantitative diagnostic method based on 99mTc-pyrophosphate scintigraphy (PYP) lateral planar images to differentiate between PYP-positive (myocardial uptake) and false-positive (blood pool uptake) scans. Methods: The study included 93 consecutive patients with suspected transthyretin amyloid cardiomyopathy (ATTR-CM) who underwent PYP between April 2022 and December 2023. Patients were categorized using planar anterior PYP images according to the Perugini visual grading system; patients with grades ≥ 2 were analyzed. Whether the uptake of the ventricle was in the blood pool or the myocardium was confirmed by transaxial single-photon emission tomography (SPECT). The heart-to-mediastinum ratios (H/M ratio) of the left lateral planar images at 1- and 3-h were calculated by placing a circular region of interest in the heart and cephalodorsal side of the heart to determine optimal cut-off values. Results: Among the PYP images, the study analyzed 15 positives diagnosed as ATTR-CM and 10 false positives. Significant differences were observed in the H/M ratio at 1- and 3-h (both p<0.01), with 100% sensitivity and specificity using cut-off values of 1.22 and 1.21 at 1- and 3-h, respectively. The interclass correlation coefficients (2, 1) between the two readers were 0.919 and 0.958 for the 1- and 3-h H/M ratios, respectively. Conclusions: Lateral planar PYP imaging can exclude PYP false-positive cases caused by blood pools in a simple and quantitative manner using only a 1-h planar image, possibly obviating the need for SPECT imaging.

Cardiac amyloidosis (CA) is a cardiac storage disease caused by the progressive extracellular deposition of misfolded proteins in the myocardium. Despite the increasing interest in this pathology, it remains an underdiagnosed condition. Non-invasive diagnostic techniques play a central role in the suspicion and detection of CA, also thanks to the continuous scientific and technological advances in these tools. The 12-lead electrocardiography is an inexpensive and reproducible test with a diagnostic accuracy that, in some cases, exceeds that of imaging techniques, as recent studies have shown. Echocardiography is the first-line imaging modality, although none of its parameters are pathognomonic. According to the 2023 ESC Guidelines, a left ventricular wall thickness ≥ 12 mm is mandatory for the suspicion of CA, making this technique crucial. Cardiac magnetic resonance provides high-resolution images associated with tissue characterization. The use of contrast and non-contrast sequences enhances the diagnostic power of this imaging modality. Nuclear imaging techniques, including bone scintigraphy and positron emission tomography, allow the detection of amyloid deposition in the heart, and their role is also central in assessing the prognosis and response to therapy. The role of computed tomography was recently evaluated by several studies, above in population affected by aortic stenosis undergoing transcatheter aortic valve replacement, with promising results. Finally, machine learning and artificial intelligence-derived algorithms are gaining ground in this scenario and provide the basis for future research. Understanding the new insights into non-invasive diagnostic techniques is critical to better diagnose and manage patients with CA and improve their survival.

Awareness of transthyretin amyloid cardiomyopathy (ATTR-CM) has increased over the years due to diagnostic and therapeutic developments. Timely initiation of novel disease-modifying treatments improves both morbidity and mortality, which underlines the necessity for a prompt diagnosis. Nevertheless, early diagnosis of ATTR-CM remains challenging. This is a retrospective observational cohort study of patients diagnosed with ATTR-CM. Between 2016 and 2023, 87 patients were diagnosed with cardiac amyloidosis of which 65 (75%) patients with ATTR-CM and 22 (25%) patients with light chain amyloidosis. This study included 65 ATTR-CM patients (mean age 77 ± 7 years; 86% male) of whom 59 (91%) with wild-type ATTR-CM (ATTRwt) and six (9%) with variant ATTR-CM. We observed a surge in ATTR-CM diagnoses from 3 patients/year (2016-2020) to 16 patients/year (2021-2023), driven by ATTRwt. Nevertheless, the interval between the onset of heart failure symptoms and ATTR-CM diagnosis has not changed significantly (2016-2020 27.3 months [18.6-62.4]; 2021-2023 30.0 months [8.6-57.2]; p = 0.546), driven by time to referral. Red flags for ATTR-CM preceded diagnosis by several years: left ventricular hypertrophy (79%, 5.8 years [3.3-7.0]) and carpal tunnel syndrome (49%, 6.8 years [2.3-12.1]). Despite the presence of typical red flags, symptom-to-diagnosis duration has remained similar driven by time to referral. Improved recognition of red flags for ATTR-CM could reduce the time to diagnosis and improve overall recognition.

Cardiac amyloidosis (CA) is caused by the misfolding, accumulation and aggregation of proteins into large fibrils in the extracellular compartment of the myocardium, leading to restrictive cardiomyopathy, heart failure and death. The major forms are transthyretin (ATTR) CA and light-chain (AL) CA, based on the respective precursor protein. Each of them requires early diagnosis for a timely treatment initiation that will improve patient outcomes. For this, radionuclide imaging is essentially used as single-photon emission computed tomography (SPECT) with bone-avid radiotracers or as positron emission tomography (PET) with amyloid-binding radiotracers. Both offer unprecedented specificity for the diagnostic of CA. SPECT has even revolutionized the diagnosis of ATTR-CA by making it non-invasive. Indeed, SPECT has now entered the standard diagnostic pathway to CA and has led to earlier diagnosis of the disease. SPECT also modified the epidemiology of ATTR-CA, highlighting that the disease is much more frequent than previously believed, and showing that ATTR-CA plays a substantial role in HFpEF and aortic stenosis, particularly among elderly patients. In parallel, amyloid-binding radiotracers for PET have accumulated a substantial amount of evidence, but are not approved for clinical use in CA yet. Further studies are needed to refine acquisition protocols and validate results in broader populations. Unlike bone-avid SPECT radiotracers, PET radiotracers have been specifically created to bind to amyloid fibrils. Thus, PET is the only imaging method that is truly specific for amyloid deposits and very sensitive to any amyloid type. Indeed, PET can not only detect ATTR-CA, but also AL-CA and rare hereditary forms. For both SPECT and PET, advances in quantitation of myocardial uptake have generated more granular and reproducible findings, paving the way for progress in earlier diagnosis, risk stratification and therapeutic response monitoring. Encouraging findings have shown that SPECT and PET are sensitive to early CA when other diagnostic methods are negative. Both radionuclide imaging techniques can predict adverse outcomes, but more evidence is needed to determine how to use them in conjunction with usual prognostic staging scores. Studies on follow-up imaging after therapy suggested that SPECT and PET can capture myocardial changes in CA, but again, more data are needed to meaningfully interpret such changes. Based on all these promising results, radionuclide imaging has the potential to further impact the landscape of CA in diagnosis, prognosis and follow-up, but also to substantially contribute to the assessment of novel therapies that will improve the lives of patients with CA.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is often accompanied by atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT), which are difficult to control because beta-blockers and antiarrhythmic drugs can worsen heart failure (HF). This study aimed to investigate the outcomes of catheter ablation (CA) for AF/AFL/AT in patients with ATTRwt-CM and propose a treatment strategy for CA.

A cohort study was conducted on 233 patients diagnosed with ATTRwt-CM, including 54 who underwent CA for AF/AFL/AT. The background of each arrhythmia and the details of the CA and its outcomes were investigated. The recurrence-free rate of AF/AFL/AT overall in ATTRwt-CM patients with multiple CA was 70.1% at 1-year, 57.6% at 2-year, and 44.0% at 5-year follow-up, but CA significantly reduced all-cause mortality [hazard ratio (HR): 0.342, 95% confidence interval (CI): 0.133-0.876, P = 0.025], cardiovascular mortality (HR: 0.378, 95% CI: 0.146-0.981, P = 0.045), and HF hospitalization (HR: 0.488, 95% CI: 0.269-0.889, P = 0.019) compared with those without CA. There was no recurrence of the cavotricuspid isthmus (CTI)-dependent AFL, non-CTI-dependent simple AFL terminated by one linear ablation, and focal AT originating from the atrioventricular (AV) annulus or crista terminalis eventually. Twelve of 13 patients with paroxysmal AF and 27 of 29 patients with persistent AF did not have recurrence as AF. However, all three patients with non-CTI-dependent complex AFL not terminated by a single linear ablation and 10 of 13 cases with focal AT or multiple focal ATs originating beyond the AV annulus or crista terminalis recurred even after multiple CA.

The outcomes of CA for ATTRwt-CM were acceptable, except for multiple focal AT and complex AFL. Catheter ablation may be aggressively considered as a treatment strategy with the expectation of improving mortality and hospitalization for HF.