BACKGROUND: There is a paucity of data regarding the impact of cardiac conduction disease (CD) on clinical outcomes in patients with cardiac amyloidosis (CA).
METHODS: The National Inpatient Sample (NIS) was queried to identify all CA admissions and those with CD using ICD-10 codes from 2016 to 2019. We explored baseline characteristics and used multivariate logistic regression to assess the association between CD and several clinical outcomes during index admission; a p-value of <0.05 was significant. Propensity score matching (PSM) was performed to validate our results.
RESULTS: A total of 12,185 patients with CA were identified. Of these, 920 (7.6 %) had CD. The median age of the sample was 72 years (IQR: 64-80). After multivariate adjustment and PSM, the presence of CD in CA was associated with higher odds of ventricular arrhythmias (VA) (aOR = 2.97, 95 % CI 1.78-4.96, p < 0.001), syncope (aOR = 3.44, 95 % CI 1.51-7.83, p = 0.003), and cardiovascular implantable electronic device (CIED) implantation (aOR = 12.86, 95 % CI 5.50-30.04, p < 0.001) but not with sudden cardiac arrest (p = 0.092), acute heart failure (p = 0.060), all-cause in-hospital mortality (p = 0.384), and non-routine discharge in patients admitted for CA (p = 0.271).
CONCLUSIONS: Although CD was not associated with all-cause in-hospital mortality, there was a significant association with VAs and syncope. Syncope is associated with worse survival in patients with CA. Further studies that prospectively follow patients are needed to determine the true effect of cardiac CD on mortality in patients with CA.

Background: In recent years, many advances have been made in the treatment of hereditary transthyretin amyloidosis (ATTRv). Patisiran is a small-interfering RNA used to treat ATTRv with only polyneuropathy or polyneuropathy and cardiomyopathy. The aim of our study was to assess the effect of patisiran on cardiac function in ATTRv patients using speckle tracking echocardiography (STE) analysis. Methods: A single-center prospective study was performed enrolling 21 patients with ATTRv (11 M-52% of the population; 10 F-48% of the population; median age 66 ± 8.4 years old). A total of 7 patients had cardiac amyloidosis and polyneuropathy, and 14 patients had only polyneuropathy without cardiac involvement. Cardiological evaluation including electrocardiograms, echocardiography with STE, and assessment of myocardial work parameters was performed in all patients before starting patisiran and after 9-18 months. Functional capacity was assessed using the 6 min walk test; quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Results: We did not find a significant difference in gender prevalence of ATTR amyloidosis in all of the population (p-value 0.79), but we found that cardiac amyloidosis significantly predominated in the male sex compared to patients with only neuropathy. In all patients, we found a slight improvement in functional capacity and quality of life. We did not find significant changes in left ventricular ejection fraction (LVEF), but we found a significant improvement in left ventricular global longitudinal strain (GLS), global work waste (GWW), and global work efficiency (GWE), especially in patients with cardiac amyloidosis; E/e\' average and left atrial stiffness also improved significantly in patients with cardiac amyloidosis. Conclusions: Our study confirms a positive effect of patisiran on cardiac function, particularly the absence of signs of subclinical deterioration as detected by very sensitive STE parameters such as GLS, MW, and atrial stiffness during follow up in patients treated with patisiran.

Left-to-right differences in the histopathologic patterns of transthyretin-derived amyloid (ATTR) deposition in the atria of older adults have not yet been investigated. Hence, this study evaluated heart specimens from 325 serial autopsy subjects. The amount of ATTR deposits in the seven cardiac regions, including both sides of atria and atrial appendages, was evaluated semiquantitatively. Using digital pathology, we quantitatively evaluated the immunohistochemical deposition burden of ATTR in the myocardium. We identified 20 sporadic ATTR cardiac amyloidosis cases (nine males). All patients had ATTR deposition in the left atrial regions of the myocardium. In the semiquantitative analysis, 14 of the 20 cases showed more severe ATTR deposition on the left atrial regions than on the right side, with statistically significant differences in the pathology grading (p < 0.01 for both the atrium and atrial appendage). Quantitative analysis further supported the difference. Moreover, six had ATTR deposition in the epineurium and/or neural fibers of the atria. Cluster analysis revealed that ATTR deposition in the myocardium was significantly more severe in males than in females. The heterogeneous distribution of amyloid deposits between atria revealed in this study may impair the orderly transmission of the cardiac conduction system and induce arrhythmias, which may be further aggravated by additional neuropathy in the advanced phase. This impairment could be more severe among males. These findings emphasize that atrial evaluation is important for individuals with sporadic ATTR cardiac amyloidosis, particularly for early detection.

OBJECTIVE: Transthyretin cardiac amyloidosis (ATTR-CA) is a frequent cause of heart failure with preserved ejection fraction (HFpEF). This study sought to determine the prevalence of ATTR-CA among HFpEF patients in a multicenter nationwide study.
METHODS: Consecutive ambulatory or hospitalized patients aged ≥ 50 years with HFpEF and left ventricle hypertrophy ≥ 12mm were studied at 20 Spanish hospitals. Screening for cardiac amyloidosis was initiated according to the usual clinical practice of each center. Positive scintigraphs were centrally analyzed.
RESULTS: 422 patients were included, of whom 387 underwent further screening for cardiac amyloidosis. A total of 65 patients (16.8%) were diagnosed with ATTR-CA, none below 75 years. There was an increase of prevalence with age. Of them, 60% were male, with a mean age of 85.3±5.2 years, mean left ventricle ejection fraction of 60.3±7.6% and a mean maximum left ventricle wall thickness of 17.2 [12-25] mm. Most of the patients were New York Heart Association class II (48.4%) or III (46.8%). Besides being older than non-ATTR-CA patients, ATTR-CA patients had higher median NT-proBNP levels (3801 [2266-7132] vs 2391 [1141-4796] pg/mL; P=.003). There was no statistical difference in the prevalence of ATTR-CA by sex (19.7% for men and 13.8% for women, P=.085). A ∼7% (4/56) of the patients exhibited a genetic variant (ATTRv).
CONCLUSIONS: This multicenter nationwide study found a prevalence of 16.8%, confirming that ATTR-CA is a significant contributor to HFpEF in male and female patients with left ventricle hypertrophy and more than 75 years.

The frequency of cardiac amyloidosis potentially present in patients with atrial fibrillation (AF) remains unclear. The purpose of this study is to determine the frequency and clinical characteristics of cardiac amyloidosis latent in AF by performing cardiac magnetic resonance imaging (MRI) in patients scheduled for AF ablation. We retrospectively analyzed 193 consecutive patients who underwent CA and cardiac MRI for atrial fibrillation. The primary endpoint of the study was the frequency of histologically confirmed cardiac amyloidosis or suspected cardiac amyloidosis [positive imaging findings on cardiac MRI strongly suspecting cardiac amyloidosis (diffuse subendocardial late gadolinium enhancement or MRI-derived extracellular volume of > 0.40)]. Among the 193 patients, 8 were confirmed or suspected cases of cardiac amyloidosis, representing a frequency of 4% (8/193 patients). Multivariate analysis identified interventricular septal thickness at end-diastole (LVSd) as an independent and significant predictor of cardiac amyloidosis (OR: 1.72, 95% CI 1.12-2.87, p = 0.020).The optimal cut-off value for IVSd was determined to be > 12.9 mm based on the Youden index. At this cut-off, the sensitivity was 75.0% (95% CI 34.9-96.8%) and the specificity was 92.3% (95% CI 87.4-95.7%), allowing for the identification of patients with definite or suspected cardiac amyloidosis. The frequency of confirmed and suspected cases of cardiac amyloidosis among patients with an IVSd > 12.9 mm was 30% (6/20 patients). In addition, prevalence of biopsy-proven cardiac amyloidosis was 10% (2/20). The prevalence of cardiac amyloidosis in atrial fibrillation patients scheduled for ablation with cardiac hypertrophy is not negligible.

OBJECTIVE: Cardiac amyloidosis (CA) is a common pathology in elderly patients that usually presents as heart failure (HF). However, it is not clear whether CA associated with HF has a worse prognosis compared with HF due to other etiologies.
METHODS: Prospective, observational cohort study that recruited patients ≥65 years of age with HF in 30 Spanish centers. The cohort was divided according to whether the patients had AC or not. Patients were followed for 1 year.
RESULTS: A total of 484 patients were included in the analysis. The population was elderly (median 86 years) and 49% were women CA was present in 23.8 % of the included patients. In the CA group, there was a lower prevalence of diabetes mellitus and valvular disease. At one year of follow-up, mortality was significantly more frequent in patients with CA compared to those without (33.0 vs.14.9%, p < 0.001). However, there were no differences between both groups in visits to the emergency room or readmissions. In the multivariate analysis, the variables that were shown to predict all-cause mortality at one year of follow-up were chronic kidney disease (HR 1.75 (1.01-3.05) p 0.045), NT-proBNP levels (HR 2.51 (1.46-4.30) p < 0.001), confusion (HR 2.05 (1.01-4.17), p 0.048), and the presence of CA (HR 1.77 (1.11-2.84), p 0.017).
CONCLUSIONS: The presence of CA in elderly patients with HF is related to a worse prognosis at one year of follow-up. Early diagnosis of the pathology and multidisciplinary management can help improve patient outcomes.

BACKGROUND: Aortic stenosis (AS) and transthyretin (ATTR) cardiac amyloidosis (CA) share the same clinical profiles and cardiac phenotype. Amyloid deposits have been frequently reported in aortic valves of patients with severe AS referred for surgical aortic valve replacement (SAVR). The aim of this study was to determine the clinical and myocardial status of patients with aortic valve amyloidosis after aortic valve surgery.
RESULTS: We performed a retrospective descriptive study of 46 patients who underwent SAVR for severe AS with amyloid deposits upon histological analysis. All patients were screened for cardiac involvement. Amyloid deposits typing was successful in 35 (76%) patients and 28 (80%) were ATTR. Two (4%) had positive bone scintigraphy and among the 5 myocardial biopsies performed during surgery, 80% were positive for ATTR deposits.
CONCLUSIONS: ATTR is the predominant type in the presence of amyloid deposits on the aortic valve after surgery for severe AS but is only rarely accompanied by cardiac uptake on bone scintigraphy. Early stages of myocardial involvement are frequent and myocardial biopsy is more sensitive for detection of mild amyloid deposits than bone scintigraphy.

UNASSIGNED: Cardiac systolic dysfunction is a poor prognostic marker in light-chain (AL) cardiomyopathy, a primary interstitial disorder; however, its pathogenesis is poorly understood.
UNASSIGNED: This study aims to analyze the effects of extracellular volume (ECV) expansion, a surrogate marker of amyloid burden on myocardial blood flow (MBF), myocardial work efficiency (MWE), and left ventricular (LV) systolic dysfunction in AL amyloidosis.
UNASSIGNED: Subjects with biopsy-proven AL amyloidosis were prospectively enrolled (April 2016-June 2021; Clinicaltrials.gov ID NCT02641145) and underwent cardiac magnetic resonance imaging (MRI) to quantify rest MBF by perfusion imaging, LV ejection fraction (LVEF) by cine MRI, and ECV by pre- and post-contrast T1 mapping. The MWE was estimated as external cardiac work from the stroke volume and mean arterial pressure normalized to the LV myocardial mass.
UNASSIGNED: Rest MBF in 92 subjects (62 ± 8 years, 52 men) with AL amyloidosis averaged 0.87 ± 0.21 ml/min/g and correlated with MWE (r = 0.42; p < 0.001). Rest MBF was similarly low in subjects with sustained hematologic remission after successful AL amyloidosis therapy (n = 21), as in those with recently diagnosed AL amyloidosis. Both MBF and MWE decreased by ECV tertile (p < 0.01 for linear trends). The association of ECV with MWE comprised a direct effect (84% of the total effect; p < 0.001) on MWE from adverse interstitial remodeling assessed by ECV and an indirect effect (16% of the total effect; p < 0.001) mediated by MBF. There was a significant base-to-apex gradient of rest MBF in subjects with higher amyloid burden.
UNASSIGNED: In AL amyloidosis, both MBF and MWE decrease as cardiac amyloid burden and ECV expansion increase. Both structural and vascular changes from ECV expansion and myocardial amyloid burden appear to contribute to lower MWE.

OBJECTIVE: Myocardial uptake on bone scintigraphy has become useful for the detection of transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to assess the prevalence of myocardial uptake in patients over 18 years of age with no clinical suspicion of cardiac amyloidosis (CA) who had undergone bone scintigraphy.
RESULTS: This was an observational, retrospective, multicenter study across 21 Spanish hospitals (September-November 2019). Of the 9864 scans analyzed (locally and centrally), incidental cardiac uptake was observed in 71 patients (0.72%), a prevalence that increased with age. A previous diagnosis of heart failure was found in 16.9% of patients with positive uptake, with >50% in NYHA II. ATTR-CA was diagnosed in 10 patients, with a mean delay of 10.4 months (95% CI: 5.1-15.7). All were >70 years old, primarily male, and had greater left ventricular hypertrophy than patients without a confirmed diagnosis (p<0.0001). ATTR-CA patients had higher rates of orthostatic hypotension (30.0% vs. 3.8% in non-ATTR-CA; p=0.025).
CONCLUSIONS: This is the first retrospective, national, multicenter study evaluating the prevalence of incidental cardiac uptake in bone scintigraphy performed for non-cardiac reasons, showing a prevalence of 0.72% in this population. Referral of these patients may facilitate early diagnosis of CA with a resulting benefit for patients.

BACKGROUND: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) with clinical phenotypes that vary across regions and genotypes. We sought to characterize the clinical characteristics of ATTR-CM in Asia.
METHODS: Data from a nationwide cohort of patients with ATTR-CM from six major tertiary centres in South Korea were analysed between 2010 and 2021. All patients underwent clinical evaluation, biochemical laboratory tests, echocardiography, and transthyretin (TTR) genotyping at the time of diagnosis. The study population comprised 105 Asian ATTR-CM patients (mean age: 69 years; male: 65.7%, wild-type ATTR-CM: 41.9%).
RESULTS: Among our cohort, 18% of the patients had a mean left ventricular (LV) wall thickness < 12 mm. The diagnosis of ATTR-CM increased notably during the study period (8 [7.6%] during 2010-2013 vs. 22 [21.0%] during 2014-2017 vs. 75 [71.4%] during 2018-2021). Although the duration between symptom onset and diagnosis did not differ, the proportion of patients with HF presenting mild symptoms increased during the study period (25% NYHA class I/II between 2010-2013 to 77% between 2018-2021). In contrast to other international registry data, male predominance was less prominent in wild-type ATTR-CM (68.2%). The distribution of TTR variants was also different from Western countries and from Japan. Asp38Ala was the most common mutation.
CONCLUSIONS: A nationwide cohort of ATTR-CM exhibited less male predominance, a proportion of patients without increased LV wall thickness, and distinct characteristics of genetic mutations, compared to cohorts in other parts of the world. Our results highlight the ethnic variation in ATTR-CM and may contribute to improving the screening process for ATTR-CM in the Asian population.