Wild-type Transthyretin Cardiac Amyloidosis Research Articles

A Novel Approach to Cardiac Magnetic Resonance Scar Characterization in Patients Affected by Cardiac Amyloidosis: A Pilot Study.

Background and Objectives: Cardiac magnetic resonance (CMR) imaging has become an essential instrument in the study of cardiomyopathies; it has recently been integrated into the diagnostic workflow for cardiac amyloidosis (CA) with remarkable results. An additional emerging role is the stratification of the arrhythmogenic risk by scar analysis and the possibility of merging these data with electro-anatomical maps. This is made possible by using a software (ADAS 3D, Galgo Medical, Barcelona, Spain) able to provide 3D heart models by detecting fibrosis along the whole thickness of the myocardial walls. Little is known regarding the applications of this software in the wide spectrum of cardiomyopathies and the potential benefits have yet to be discovered. In this study, we tried to apply the ADAS 3D in the context of CA. Materials and Methods: This study was a retrospectively analysis of consecutive CMR imaging of patients affected by CA that were treated in our center (Marche University Hospital). Wherever possible, the data were processed with the ADAS 3D software and analyzed for a correlation between the morphometric parameters and follow-up events. The outcome was a composite of all-cause mortality, unplanned cardiovascular hospitalizations, sustained ventricular arrhythmias (VAs), permanent reduction in left ventricular ejection fraction, and pacemaker implantation. The secondary outcomes were the need for a pacemaker implantation and sustained VAs. Results: A total of 14 patients were deemed eligible for the software analysis: 8 patients with wild type transthyretin CA, 5 with light chain CA, and 1 with transthyretin hereditary CA. The vast majority of imaging features was not related to the composite outcome, but atrial wall thickening displayed a significant association with both the primary (p = 0.003) and the secondary outcome of pacemaker implantation (p = 0.003). The software was able to differentiate between core zones and border zones of scars, with the latter being the most extensively represented in all patients. Interestingly, in a huge percentage of CMR images, the software identified the highest degree of core zone fibrosis among the epicardial layers and, in those patients, we found a higher incidence of the primary outcome, without reaching statistical significance (p = 0.18). Channels were found in the scar zones in a substantial percentage of patients without a clear correlation with follow-up events. Conclusions: CMR imaging plays a pivotal role in cardiovascular diagnostics. Our analysis shows the feasibility and applicability of such instrument for all types of CA. We could not only differentiate between different layers of scars, but we were also able to identify the presence of fibrosis channels among the different scar zones. None of the data derived from the ADAS 3D software seemed to be related to cardiac events in the follow-up, but this might be imputable to the restricted number of patients enrolled in the study.

Wild-Type Transthyretin Cardiac Amyloidosis is Not Rare in Elderly Subjects: the CATCH Screening Study.

Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) affects older adults and is currently considered as a rare disorder. We investigated for the first time the prevalence of ATTRwt-CA in elderly individuals from the general population. General practitioners from Pisa, Italy, proposed a screening for ATTRwt-CA to all their patients aged 65-90 years, until 1,000 accepted. The following red flags were searched: interventricular septal thickness ≥12 mm, any echocardiographic, ECG or clinical hallmark of CA, or high sensitivity-troponin T ≥14 ng/L. Individuals with at least one red flag (n=346) were asked to undergo the search for a monoclonal protein and bone scintigraphy, and 216 accepted. Four patients received a non-invasive diagnosis of ATTRwt-CA. All complained of dyspnea on moderate effort. A woman and a man aged 79 and 85 years, respectively, showed an intense cardiac tracer uptake (grade 3), left ventricular (LV) wall thickening, grade 2 to 3 diastolic dysfunction, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) >1,000 ng/L. Two other patients (a man aged 74 years and a woman aged 83 years) showed a grade 2 uptake, an increased LV septal thickness, but preserved diastolic function, and NT-proBNP <300 ng/L. The prevalence of ATTR-CA in subjects ≥65 years was calculated as 0.46% (i.e., 4 out of the 870 subjects completing the screening, namely 654 not meeting the criteria for Step 2 and 216 progressing to Step 2). ATTRwt-CA is uncommon in elderly subjects from the general population, but more frequent than expected for a rare disease.

Performance of 99mTc-PYP scintigraphy in the diagnosis of hereditary transthyretin cardiac amyloidosis.

Most reported research has primarily investigated wild-type transthyretin cardiac amyloidosis (ATTRwt-CA). However, the application of bone scintigraphy for hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has not been systematically investigated. Therefore, in this study, we aimed to evaluate the diagnostic value of 99mTc-PYP scintigraphy in ATTRv-CA. Fifty-four patients were enrolled in a highly suspected cardiac amyloidosis cohort. Transthyretin (TTR) gene characteristics were summarized in the ATTRv-CA group. In 99mTc-PYP scintigraphy, the diagnostic efficiency of the visual score (VGS) and heart-to-contralateral chest (H/CL) ratio were evaluated. Furthermore, the interobserver consistency among the diagnosticians was investigated. Twenty-eight patients were diagnosed with ATTRv-CA with eight genotypes. The Ala97Ser genotype accounts for 46% (n = 13) with a mean age of disease onset, definite diagnosis, and interval of 61.6 ± 1.9, 66.5 ± 1.3, and 4.0 (3.0, 6.2) years, respectively. Their VGS is Grade 3, and their H/CL ratio is higher than that of the non-Ala97Ser group, but no statistical significance exists (mean H/CL: 1.95 ± 0.06 vs. 1.87 ± 0.02, p = 0.844). Additionally, ATTRv-CA patients showed VGS ≥ 2, and mean H/CL ratio of 2.09 ± 0.06. The sensitivity and specificity of VGS were 100% and 65%, respectively. And the interobserver consistency analysis of VGS showed the intraclass correlation coefficient is 0.522. The best cutoff value of H/CL ratio was 1.51 (AUC = 0.996), and the diagnostic consistency of H/CL (bias: 0.018) was high. Ala97Ser is the most common genotype in ATTRv-CA in our cohort, with characteristics of later onset and rapid progression, but delayed diagnosis and extensive 99mTc-PYP uptake. Overall, ATTRv-CA patients showed moderate-to-extensive myocardial 99mTc-PYP uptake. Additionally, VGS carries subjectivity, low specialty and interobserver consistency. But H/CL exhibit high diagnostic efficacy and interobserver consistency. The H/CL ratio is more useful than VGS.

Effects of tafamidis on the left ventricular and left atrial strain in patients with wild-type transthyretin cardiac amyloidosis.

Although tafamidis is used in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA), its specific effect on cardiac function is unclear. Thus, this study aimed to investigate the effect of tafamidis on left atrial (LA) and left ventricular function using speckle-tracking echocardiography for 1 year of treatment in patients with ATTRwt-CA. We included 23 patients (mean age, 76 years) with ATTRwt-CA confirmed via biopsy. We analysed the left ventricular and LA strain using 2D speckle-tracking echocardiography and compared these parameters before and 1 year after starting treatment with tafamidis between 16 patients with sinus rhythm (SR) and 7 patients with atrial fibrillation (AF). In ATTRwt-CA patients with SR, LA reservoir strain significantly improved by 1-year tafamidis treatment (10.5 ± 5.0% to 11.9 ± 5.3%, P = 0.0307) although global longitudinal strain (GLS) did not (-10.6 ± 3.1% to -11.3 ± 3.0%, P = 0.0608). In contrast, LA reservoir strain was not significantly changed (5.4 ± 2.9% to 4.9 ± 1.7%, P = 0.4571), and GLS deteriorated (-8.4 ± 2.3% to -6.8 ± 1.4%, P = 0.0267) in ATTRwt-CA patients with AF. LA function improved with tafamidis treatment in ATTRwt-CA patients with SR but not left ventricular function. However, these cardiac functions did not improve with tafamidis treatment in ATTRwt-CA patients with AF.

Impact of SARS-CoV-2 infection in patients with cardiac amyloidosis: Results of a multicentre registry

BackgroundDescriptions on impact of SARS-CoV-2 infection in patients with cardiac amyloidosis (CA) are lacking. Our aim was to describe the prognosis of those patients. MethodsRetrospective observational study of unvaccinated patients with CA who developed SARS-CoV-2 infection enrolled in eleven centres (March 2020 to May 2021). Descriptive analysis of basal characteristics, hospitalization, mortality, and severe clinical course was performed. Comparisons to a population-based control group were made. ResultsForty-one patients were identified. Most patients had wild-type transthyretin CA (61%) and were on NYHA Class II–III (80.5%). CA patients were commonly hospitalized (73.2%) and those were more symptomatic than outpatients (p=0.035). The 24.4% of CA patients died as consequence of SARS-CoV-2 infection. Patients with CA had an increased risk of hospitalization [OR 6.23 (3.05–12.74), p<0.001] and mortality [OR 2.18 (1.01–4.68), p=0.047] when compared to control population after adjustment by age and sex. After a medium follow-time of 311 days, 41.5% of the CA cohort died. ConclusionsSARS-CoV-2 infection is associated with high mortality and hospitalization rates in patients with CA, which exceed that expected by their sex and advanced age.

Prevalence of cardiac amyloidosis in patients undergoing carpal tunnel release with amyloid deposition in removed tenosynovium

Abstract Background Carpal tunnel syndrome (CTS) is an early symptom and important clinical indicator for the diagnosis of cardiac amyloidosis. Amyloid deposition in removed tenosynovium during carpal tunnel release (CTR) is often confirmed; however, the prevalence of concomitant cardiac amyloidosis is not yet understood. Purpose This study aimed to evaluate the prevalence of amyloid deposition in removed tenosynovium in patients who underwent CTR and to clarify the prevalence of concomitant cardiac amyloidosis in patients who had amyloid deposition in removed tenosynovium. Methods Overall, 669 patients who underwent CTR were prospectively examined and evaluated for amyloid deposition after tenosynovium removal. Invitation and proposal letters for cardiac screening were sent to patients with amyloid deposition. Electrocardiography, echocardiography, and biomarkers were evaluated to assess the likelihood of cardiac amyloidosis. Results Amyloid deposition was observed in 261 (39%) patients, who were significantly older and predominantly male (p&amp;lt;0.05). Among them, 111 patients (mean age; 70.8 ± 7.3 years old; men: 55%) agreed to cardiac screening. 99mTc-labeled pyrophosphate (99mTc-PYP) scintigraphy was performed in 12 patients who met the following criteria: 1) interventricular septum diameter (IVSd) ≥14 mm or 2) 12 mm ≤ IVSd &amp;lt;14 mm with above-normal limits in high-sensitivity cardiac troponin T (hs-cTnT; &amp;gt;0.014 ng/mL). Six patients (50%) had positive findings on 99mTc-PYP scintigraphy and were diagnosed with wild-type transthyretin cardiac amyloidosis with Mayo prognostic stage I. The prevalence of concomitant cardiac amyloidosis was observed in 6/111 (5.4%) CTR patients with amyloid deposition and 50% (6/12) in patients with left ventricular hypertrophy (≥12 mm) with increased hs-cTnT levels. Conclusion Amyloid deposition in removed tenosynovium was frequently observed in elderly men with CTS. Cardiac screening may be useful for the early diagnosis of cardiac amyloidosis in patients undergoing CTR with amyloid deposition. This knowledge should be shared with orthopedic surgeons and cardiologists for the early diagnosis of cardiac amyloidosis.Flowchart of participant selectionGraphical Abstract

Advanced echocardiographic assessment in wild-type and hereditary transthyretin cardiac amyloidosis: the role of myocardial work and left atrial strain

Abstract Introduction Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive infiltrative cardiomyopathy caused by extracellular deposition of insoluble transthyretin (TTR) amyloid fibrils in the myocardium. ATTR-CA can be classified as wild type ATTR-CA (ATTRwt-CA), caused by age-related misfolding of TTR, and hereditary ATTR-CA (ATTRv-CA), an autosomal dominant disease in which gene mutations lead to changes in TTR protein. Speckle tracking echocardiography and myocardial work (MW) analysis can better characterize left ventricular and left atrial (LA) function in ATTRwt-CA and in ATTRv-CA. Aims to investigate differences in myocardial work and left atrial strain parameters between patients affected by ATTRwt-CA and patients affected by ATTRv-CA. Material and methods 40 male patients affected by ATTR-CA were prospectively enrolled, distinguishing between 20 patients with ATTRwt-CA (76 ± 7 yrs) and 20 patients with ATTRv-CA (74 ± 6 yrs) (1 pts with Val30Met mutation, 6 pts with Val122Ile mutation; 8 pts with Glu89Gln mutation; 5 pts with Phe64Leu mutation). All underwent a transthoracic echcoardiogram to calculate global longitudinal strain (GLS), MW parameters and LA strain. Results No difference was found between the two groups (ATTRwt-CA vs ATTRv-CA) for what regards age (76 ± 7 vs 74 ± 6 yrs, p = 0,06), BMI (27,2 ± 2,2 vs 26,6 kg/mq; p = 0,3), BSA (1,8 ± 0,2 vs 1,7 ± 0,1 mq; p = 0,1) and left ventricle mass index (LVMi) (183,41 ± 45,2 vs 148,5 ± 47,3 g/mq; p = 0,07). In ATTRwt-CA patients, ejection fraction (EF) is lower, but without any statistical significance (50 ± 6,9 vs 54 ± 6,4 %, p = 0,06). On the other hand, in ATTRwt-CA patients GLS is significantly higher than in ATTRv-CA patients (-9,8 ± 3,2 vs -15,0 ± 2,5 %; p &amp;lt; 0,0001). Global work index (GWI) (853,6 ± 367,6 vs 1431,6 ± 318,3 mmHg%; p &amp;lt; 0,0001), global constructive work (GCW) (1169 ± 303 vs 1726,5 ± 310,3 mmHg %; p &amp;lt; 0,0001) and global work efficiency (GWE) (83,2 ± 9,4 vs 89 ± 5,3 %; p = 0,04) are significantly reduced in ATTRwt-CA in comparison with ATTRv-CA. For what regards atrial function, in ATTwt-CA patients LA reservoir (9,7 ± 3,7 vs 17,6 ± 7,5 %; p = 0,004) and LA ejection fraction (LAFE) (28,9 ± 13,6 vs 46,2 ± 8,9; p = 0,02) are reduced, while LA booster is higher (-2,5 ± 3,1 vs -10 ± 4,7 %; p &amp;lt; 0, 0001). Conclusion In patients with ATTR-CA advanced echocardiographic assessment can better differentiate left atrial and left ventricular involvement in ATTRwt-CA versus ATTRv-CA.TablesGraphs

Abstract 16467: The Prevalence, Racial Distribution, and In Hospital Outcome of Percutaneous Coronary Intervention in Non ST Elevation Myocardial Infarction With Patients With Wild Type Transthyretin Cardiac Amyloidosis

Introduction: Epicardial coronary arteries are also a target for intramural amyloid deposits in cardiac amyloidosis beyond the myocardium. For patients with restrictive cardiomyopathy and some degree of stable chronic angina, the role of coronary revascularization has not been clearly shown to have additional benefits over medical management. In unstable angina and Non-ST-elevation acute coronary syndrome (NSTE-ACS) population, isolated observations have painted a grimmer prognosis. Hypothesis: We hypothesized that wild-type ATTR-CA patients with NSTEMI undergoing Percutaneous coronary interventions (PCI) had poor outcomes. We sought to establish their prevalence and uncover the determinants of these outcomes. Methods: A five-year retrospective inquiry of the National Inpatient Sample (NIS) database from 2016 to 2020 on all the patients admitted with a matching diagnosis to the ICD-10 code of interest. Results: Over the five-year span of our observation, about 1,116,170 patients were admitted to the hospital in the US with an NSTE-ACS diagnosis, of which 99% underwent PCI during the same hospitalization (1,116,065). Among the latter 1,505 patients (1%) had ATTR-CA. The most represented demographics in that subpopulation were men (69%), elderly about 74 years old on average (80%), and Whites (60%). The cumulative mortality rate among the ATTR-CA PCI group was higher (18%) than the general NSTE-ACS PCI (14%). Factors associated with survival at hospital discharge were female sex (p-value 0.008), and black race (p-value 0.019). Meanwhile, Asian race (p-value 0.0001), being in a teaching hospital (p-value 0.0001), medium to large size hospital (p-value 0.0001) were harbingers of poor outcomes including death (18%), prolonged hospitalization (about 9.5 days), and higher healthcare costs (about $127,319). Conclusions: PCI has mortality benefits in STEMI and unstable CAD. However, in the ATTR-CA with unstable CAD, this might not be the case as seen with the staggering 28% risk increase in mortality rates in our study. Percutaneous revascularization in wild-type ATTR-CA deserves its own category when clinicians are weighing the benefits and a multidisciplinary approach should be preferred.

Two autopsy cases of wild-type transthyretin cardiac amyloidosis who died 10 days after technetium-99m-pyrophosphate scintigraphy

Two autopsy cases of wild-type transthyretin cardiac amyloidosis who died 10 days after technetium-99m-pyrophosphate scintigraphy

Incidence and determinants of atrial fibrillation in patients with wild-type transthyretin cardiac amyloidosis

BackgroundData on the incidence and factors associated with de novo atrial fibrillation (AF) in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is limited. We described the incidence and factors associated with de novo AF in patients diagnosed with ATTRwt-CA to drive tailored arrhythmia screening. MethodsMulticenter, retrospective, observational cohort study performed in six referral centers for CA. All consecutive patients diagnosed with ATTRwt-CA between 2004 and 2020 with >6-month follow up (FU) were enrolled and divided into three groups according to presence of AF: (1)patients with ‘known AF’; (2)patients in ‘sinus rhythm’ and (3)patients developing ‘de novo AF’ during FU. Incidence and factors associated with AF in patients with ATTRwt were the primary outcomes. ResultsOverall, 266 patients were followed for a median of 19 [11−33] months: 148 (56%) with known AF, 84 (31.6%) with sinus rhythm, and 34 (12.8%) with de novo AF. At Fine-Gray competing risk analysis to account for mortality, PR (sub-distribution hazard ratio [SHR] per Δms: 1.008, 95% C.I. 1.001–1.013, p = 0.008), QRS (SHR per Δms: 1.012, 95% C.I. 1.001–1.022, p = 0.046) and left atrial diameter ≥ 50 mm (SHR: 2.815,95% C.I. 1.483–5.342, p = 0.002) were associated with de novo AF. Patients with at least two risk factors (PR ≥ 200 ms, QRS ≥ 120 ms or LAD≥50 mm) had a higher risk of developing de novo AF compared to patients with no risk factors (HR 14.918 95% C.I. 3.242–31.646, p = 0.008). ConclusionsAt the end of the study almost 70% patients had AF. Longer PR and QRS duration and left atrial dilation are associated with arrhythmia onset.

Impact of SARS-CoV-2 infection in patients with cardiac amyloidosis: Results of a multicentre registry

BackgroundDescriptions on impact of SARS-CoV-2 infection in patients with cardiac amyloidosis (CA) are lacking. Our aim was to describe the prognosis of those patients. MethodsRetrospective observational study of unvaccinated patients with CA who developed SARS-CoV-2 infection enrolled in eleven centres (March 2020 to May 2021). Descriptive analysis of basal characteristics, hospitalization, mortality, and severe clinical course was performed. Comparisons to a population-based control group were made. ResultsForty-one patients were identified. Most patients had wild-type transthyretin CA (61%) and were on NYHA Class II–III (80.5%). CA patients were commonly hospitalized (73.2%) and those were more symptomatic than outpatients (p=0.035). The 24.4% of CA patients died as consequence of SARS-CoV-2 infection. Patients with CA had an increased risk of hospitalization [OR 6.23 (3.05–12.74), p<0.001] and mortality [OR 2.18 (1.01–4.68), p=0.047] when compared to control population after adjustment by age and sex. After a medium follow-time of 311 days, 41.5% of the CA cohort died. ConclusionsSARS-CoV-2 infection is associated with high mortality and hospitalization rates in patients with CA, which exceed that expected by their sex and advanced age.

Strain-derived myocardial work in wild-type transthyretin cardiac amyloidosis with aortic stenosis-diagnosis and prognosis.

Several echocardiographic parameters have been suggested to differentiate wild-type transthyretin cardiac amyloidosis (ATTRwt) from other causes of hypertrophy. These studies have all been performed in small samples of mixed cardiac amyloidosis. The purpose of this study was to investigate the role of echocardiographic parameters in patients with ATTRwt and aortic stenosis (AS) versus patients with AS. The secondary aim was to investigate the role of myocardial work in the prognosis of patients with ATTRwt. The sensitivity and specificity of the relative apical sparing ratio (RAS), the apical-to-basal ratio (AB), the ejection-fraction-to-global-longitudinal-strain ratio (EF/GLS), and the global myocardial work index (GWI) were calculated using receiver-operated characteristics curves and area under the curve (AUC) in patients with ATTRwt and AS (n=50) versus patients with AS (n=354). Multivariable regression was used to assess the prognostic value of GWI in patients with ATTRwt (n=212). When used to identify AS from ATTRwt+AS, GWI had a sensitivity of 80% and specificity of 70%. The AUC of GWI was larger than that of AB (p=.01) and EF/GLS (p>.01) but not RAS (p=.15). In patients with ATTRwt multivariable regression found age predicted mortality with an estimate of HR=1.086 (CI: 1.034-1.141) while GWI predicted survival with an estimate of HR=.837 (CI: .733-.956) per 100mmHg*% increase. GWI was demonstrated to be a viable classifier in ATTRwt and AS versus AS. GWI was demonstrated to independently predict survival in patients with ATTRwt. Further studies examining the role of myocardial work in ATTRwt are warranted.

Prevalence of Cardiac Amyloidosis in Patients Undergoing Carpal Tunnel Release With Amyloid Deposition.

Carpal tunnel syndrome (CTS) is considered an early sign of cardiac amyloidosis (CA) because amyloid deposition is often confirmed in the tenosynovium removed during carpal tunnel release (CTR); however, the prevalence of concomitant CA is unclear.Methods and Results: We prospectively examined 700 patients who underwent CTR and evaluated amyloid deposition after tenosynovium removal. Amyloid deposition was observed in 261 (37%) patients, who were significantly older and predominantly male (P<0.05). Of them, 120 agreed to cardiac screening. We performed 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy in 12 patients who met either of the following criteria: (1) interventricular septal diameter (IVSd) ≥14 mm or (2) 12 mm ≤ IVSd < 14 mm with above-normal limits in high-sensitivity cardiac troponin T (hs-cTnT). Six patients (50%) had positive findings on 99 mTc-PYP scintigraphy and were diagnosed with wild-type transthyretin CA. Concomitant CA was observed in 6/120 (5%) CTR patients with amyloid deposition and 50% (6/12) in patients with left ventricular hypertrophy (≥12 mm) with increased hs-cTnT levels. Amyloid deposition was frequently observed in the removed tenosynovium of elderly men with CTS. Cardiac screening may be useful for early diagnosis of CA in patients undergoing CTR with amyloid deposition.

Technetium-99m-pyrophosphate imaging-based computed tomography-guided core-needle biopsy of internal oblique muscle in wild-type transthyretin cardiac amyloidosis

Background Technetium-99m-pyrophosphate (99mTc-PYP) uptake in the internal oblique muscle (IOM), which is often observed in patients with wild-type transthyretin cardiac amyloidosis (ATTR-CA), indicates amyloid transthyretin (ATTR) deposition. Objective This study aimed to assess the safety and efficacy of 99mTc-PYP imaging-based computed tomography (CT)-guided core-needle biopsy of the IOM as a new extracardiac screening biopsy for confirming the presence of ATTR deposits. Methods Patients with suspected ATTR-CA in whom myocardial tracer uptake was detected on chest- and abdomen-centered images of 99mTc-PYP scintigraphy underwent CT-guided core-needle biopsy at the site with the highest tracer uptake in the IOM between September 2021 and November 2022. Results All 18 consecutive patients (mean age, 86.3 years ± 6.5; 61.1% male) enrolled in the study showed 99mTc-PYP uptake into the IOM. Adequate tissue samples were obtained from all patients except one without serious complications. Immunohistochemical analysis confirmed ATTR deposits in 16/18 (88.9%) patients. In the remaining two patients, ATTR deposits were observed via endomyocardial biopsy. All patients were diagnosed with wild-type ATTR-CA based on transthyretin gene sequence testing results. Conclusion In wild-type ATTR-CA, 99mTc-PYP imaging-based CT-guided core-needle biopsy of the IOM could be used as an extracardiac screening biopsy to confirm the presence of ATTR deposits.

PO-03-232 PROGNOSTIC IMPACT OF NON-SUSTAINED VENTRICULAR TACHYCARDIA IN WILD-TYPE TRANSTHYRETIN CARDIAC AMYLOIDOSIS

Non-sustained ventricular tachycardia (NSVT) detected on rhythm monitoring is common in AL amyloidosis, but data on its prevalence and prognostic impact in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) are sparse. To investigate the prevalence of NSVT detected during clinically-indicated ambulatory Holter monitoring and its association with incident sustained VT and ventricular fibrillation (VF) in ATTRwt-CA patients. A single-center retrospective cohort of ATTRwt-CA patients without known history of sustained VT/VF was included (2011-2022). The presence and characteristics of NSVT (≥3 beats) at the first Holter after the ATTRwt-CA diagnosis at our institution were documented. The endpoint was the first occurrence of sustained VT or VF recorded by an implantable cardioverter-defibrillator (ICD) or other methods (in patients without ICD), and it was comparatively assessed in patients with and without NSVT with Kaplan-Meier analysis. Multivariate Cox regression analyses using stepwise variable selection were also performed to identify predictors of incident VT/VF. A total of 219 patients with ATTRwt-CA were included (mean age 74.9 years; 95% males; mean LVEF 52%). Of them, 8 had an ICD at baseline while 14 underwent ICD implantation within a 6-month window from baseline. Mean Holter monitoring duration was 25.6 hours and 53% of patients had at least one NSVT run at index Holter monitor with mean total ventricular ectopy burden 3.8%. After mean follow up 35.2 months, 17 patients experienced the primary outcome. Patients with NSVT had a lower survival free of VT/VF compared to those without NSVT (log-rank p=0.01; figure). In multivariable analysis, the presence of NSVT (HR 3.95, 95% CI 1.10-14.0) and the number of NSVT runs (HR 1.003, 95% 1.00-1.01, per run) were significant predictors of future VT/VF. NSVT is highly prevalent among patients with ATTRwt-CA and confers an increased risk of incident sustained ventricular arrhythmias. This finding has implications in the risk stratification and decision-making for the prevention of sudden cardiac death in these patients.

580 INCIDENCE AND FACTORS ASSOCIATED WITH DE NOVO ATRIAL FIBRILLATION IN PATIENTS WITH WILD-TYPE TRANSTHYRETIN CARDIAC AMYLOIDOSIS - A MULTICENTER STUDY

Abstract Purpose We described the incidence and ECG factors associated with de novo atrial fibrillation (AF) in patients diagnosed with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) to drive tailored arrhythmia screening. Background Data on the incidence rate and factors associated with de novo AF in patients with ATTRwt CA is limited. Methods Multicenter, retrospective, observational cohort study performed in six referral centers for CA. All consecutive patients diagnosed with ATTRwt-CA between 2004 and 2020 with &amp;gt;1-year follow up (FU) were enrolled in the study and were divided into three groups according to presence of AF: (1)patients with ‘known AF’; (2)patients in ‘sinus rhythm’ and (3)patients developing ‘de novo AF’ during FU. Incidence and factors associated with AF in patients with ATTRwt were the primary outcomes. Results Overall, 266 patients were followed for a median of 469 days: 148 (56%) with known AF, 84 (31.6%) with sinus rhythm, and 34 (12.8%) with de novo AF. Age and gender were similarly distributed. At multivariable analysis, PR (Hazard Ratio[HR]: 1.008 95% C.I. 1.001-1.016), QRS (HR: 1.022 95% C.I. 1.002-1.043) and left atrial dilatation&amp;gt;50mm (HR: 3.429 95% C.I. 1.565-7.329) were associated with de novo AF at FU. Patients presenting with at least two risk factors (PR&amp;gt;200ms, QRS&amp;gt;120ms or LAD&amp;gt;50mm) had a higher risk of developing de novo AF compared to patients with no risk factors (HR 14.918 95% C.I. 3.242-31.646). Conclusions Incidence of de novo AF in patients with ATTRwt is 20.7%/year. Longer PR and QRS duration and left atrial dilation are associated with arrhythmia onset.

Incidence and factors associated with de novo atrial fibrillation in patients with wild-type transthyretin cardiac amyloidosis

Abstract Purpose We described the incidence and ECG factors associated with de novo atrial fibrillation (AF) in patients diagnosed with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) to drive tailored arrhythmia screening. Background Data on the incidence rate and factors associated with de novo AF in patients with ATTRwt-CA is limited. Methods Multicenter, retrospective, observational cohort study performed in six referral centers for CA. All consecutive patients diagnosed with ATTRwt-CA between 2004 and 2020 with &amp;gt;1-year follow up (FU) were enrolled in the study and were divided into three groups according to presence of AF: (1) patients with “known AF”; (2) patients in “sinus rhythm” and (3) patients developing “de novo AF” during FU. Incidence and factors associated with AF in patients with ATTRwt were the primary outcomes. Results Overall, 266 patients were followed for a median of 469 days: 148 (56%) with known AF, 84 (31.6%) with sinus rhythm, and 34 (12.8%) with de novo AF. Age and gender were similarly distributed. At multivariable analysis, PR (Hazard Ratio [HR]: 1.008; 95% CI: 1.001–1.016), QRS (HR: 1.022; 95% CI: 1.002–1.043) and left atrial dilatation &amp;gt;50mm (HR: 3.429, 95% CI: 1.565–7.329) were associated with de novo AF at FU. Patients presenting with at least two risk factors (PR &amp;gt;200ms, QRS &amp;gt;120ms or LAD &amp;gt;50mm) had a higher risk of developing de novo AF compared to patients with no risk factors (HR 14.918; 95% CI: 3.242–31.646). Conclusions Incidence of de novo AF in patients with ATTRwt is 20.7%/year. Longer PR and QRS duration and left atrial dilation are associated with arrhythmia onset. Funding Acknowledgement Type of funding sources: None.

Identification of wild-type transthyretin cardiac amyloidosis in patients with carpal tunnel syndrome surgery (CACTuS).

Wild-type transthyretin cardiac amyloidosis (ATTRwt) is an infiltrative cardiomyopathy with a poor prognosis. The condition is associated with carpal tunnel syndrome (CTS), which often precedes the ATTRwt diagnosis by several years. The aim of the study was (i) to screen patients with a recent history of CTS for ATTRwt using red flags, (ii) to determine whether patients with screened ATTRwt had less advanced disease compared with patients with clinical ATTRwt, and (iii) to assess the sensitivity and specificity of known red flags in ATTRwt. Patients aged ≥60years at the time of CTS surgery were invited for screening. Red flags were defined as elevated biomarker levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) or cardiac troponin, an electrocardiogram pattern associated with ATTRwt, left ventricular hypertrophy (LVH), and impaired longitudinal strain with apical sparring. All patients with a red flag were referred for a diagnostic scintigraphy. Patients with ATTRwt diagnosed by screening were compared with patients with clinical ATTRwt (n=51) matched by age, gender, and CTS surgery. Among the 120 enrolled subjects (mean age 74.5years, 90% male), the suspicion of ATTR was raised in 67 (55.8%), and 10 (8.3%) were diagnosed with ATTRwt. Patients identified with ATTRwt were predominantly asymptomatic and had mildly elevated NT-proBNP, mildly increased LVH, preserved left ventricular ejection fraction, and systolic longitudinal function, which differed significantly from clinical ATTRwt controls (P<0.001). The study found an ATTRwt prevalence of 8.3% in a population of age and gender-selected patients with a recent history of CTS. The identified patients with ATTRwt had less structural and functional cardiac involvement than clinical ATTRwt controls.

Assessment of clinical characteristics of cardiac amyloidosis as a potential underlying etiology in patients diagnosed with heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is heterogeneous clinical syndrome. Transthyretin cardiac amyloidosis (CA) is an underdiagnosed cause of HFpEF. Red flags are extremely useful for suspecting CA. We aimed to evaluate the frequency of cardiac and extracardiac manifestations of CA in HFpEF patients based on red flags. Baseline characteristics of 85 patients were recorded during admission. Electrocardiogram and echocardiography were performed. All patients were examined for red flags. Cardiac scintigraphy was performed in 85 patients. The mean (standard deviation [SD]) age of the study group was 67.9 (9.8) years, and 52 (61.2%) patients were female. At least 1 red flag was observed in 67% of HFpEF patients. Only 4 of the patients had more than 3 red flags. The mean number of red flags in a patient with HFpEF was 1.3. Extracardiac clinical red flags were observed in only 9 (10.5%) patients. Cardiac clinical red flags were extremely rare. An electrocardiographic red flag was detected in 2 out of 10 patients and an echocardiographic red flag in 4 out of 10 patients with HFpEF. Scintigraphy showed that 17.6% of all patients have had a grade 2 or 3 cardiac uptake. The patients with wild-type transthyretin CA had twice as many red flags as those without. The results of the study showed that patients diagnosed with HFpEF had an average of 1.3 red flags suggestive of CA. In real life, extracardiac red flags are rare, while electrocardiographic and echocardiographic red flags are more common in patients with HFpEF.

Early Experience of Tafamidis Treatment in Japanese Patients With Wild-Type Transthyretin Cardiac Amyloidosis From the Kochi Amyloidosis Cohort.

Tafamidis has emerged as an effective treatment for patients with wild-type transthyretin cardiac amyloidosis (ATTRwt CA). The early experience of tafamidis treatment for Japanese patients with ATTRwt CA is reported here.Methods and Results: Over the past 2 years, in 82 patients with ATTRwt CA (mean age of 81.7±6.0 years), tafamidis treatment was initiated for 38 patients. The remaining 44 patients were not administered tafamidis. The most frequent reason for non-administration of tafamidis was advanced heart failure and the second most reason was the patient's frailty. In patients who received tafamidis treatment, there was no discontinuation of tafamidis due to adverse events, the rate of cardiovascular-related hospitalizations per year was 0.19, and the 1-year survival rate was 92%. In the patients who continued tafamidis for 12-18 months, there was no significant deterioration from baseline for high-sensitivity cardiac troponin T level, plasma B-type natriuretic peptide level, left ventricular ejection fraction, inter-ventricular septum wall thickness, or value of left ventricular longitudinal strain. Tafamidis treatment was introduced for approximately half of the study patients with ATTRwt CA in real-world practice. Tafamidis is likely to be safe and may maintain the status of disease severity in the short-term in selected Japanese patients with ATTRwt CA. Further research is needed to determine appropriate patient selection for tafamidis treatment and efficacy of tafamidis in the long term.