Risultati per: Low Back Pain: raccomandazioni

Circulation, Volume 146, Issue Suppl_1, Page A14857-A14857, November 8, 2022. Background:Management of patients with paradoxical (ejection fraction > 50%) low gradient (< 40 mm Hg mean) severe (valve area < 1 cm2) aortic stenosis (PLAS) on ECHO is controversial. We studied the role of invasive hemodynamics (CATH) in evaluating these patients.Methods:In this single center retrospective cohort study, patients who underwent CATH for evaluation of PLAS on ECHO were divided into a “concordant” group (CG) when CATH aortic valve area (AVA) was < 1.0 cm2and a “discordant” group (DG) when CATH AVA was > 1.0 cm2. ECHO features, aortic valve replacement (AVR), and all-cause mortality were compared between the two groups. T-test, Chi-square test, and Kaplan-Meier analysis were performed. P-value of < 0.05 was considered statistically significant.Results:Among 76 PLAS patients who underwent CATH, the AVA was discordant in 21/76 (27.6%). DG patients were younger (72.2 vs. 78.7 y, p = 0.008). Other demographics including the Charlson comorbidity index (CCI) were similar. Dimensionless index (DI) was lower in CG than in DG (0.24 ±0.042 vs. 0.274 ± 0.041, p = 0.002) and % with DI < 0.25 was higher in CG (55.6% vs. 28.7%, p = 0.03). Other ECHO parameters including mean gradient, left ventricular outflow tract (LVOT) diameter, Vmax LVOT, AVAi, stroke volume index, and flow rate (AVA x mean velocity) were not different. More patients underwent AVR in CG (49/55, 89%) compared to DG (12/21, 57%, p = 0.001). Overall survival based on all-cause mortality was similar after AVR in both groups (p = 0.695, median follow up 1105.5 days). In DG, survival was better with AVR than with medical therapy alone (p = 0.049). CCI was not different in patients with AVR versus those without (p = 0.102).Conclusion:¼ of patients with PLAS on ECHO had discordant AVA on CATH. DI < 0.25 occurred more frequently in the CG cohort. Even in the DG, survival was better with AVR.Clinical Implication:AVR confers a survival advantage in patients with PLAS on ECHO, and should be considered regardless of AVA on CATH.

Circulation, Volume 146, Issue Suppl_1, Page A12585-A12585, November 8, 2022. Background:High-dose ionizing radiation is a well-established risk factor for childhood malignancies, including hematopoietic cancers (HC). However, data on the effect of low-dose ionizing radiation (LDIR) from medical imaging is conflicting and scant, especially in the pediatric population with congenital heart diseases (CHD). This study evaluated the association between cardiac LDIR exposure and hematopoietic cancers among children with CHD.Methods:A nationwide population-based cohort study was conducted using the Canadian Congenital Heart Disease (CanCHD) database. The study population included children born between 1999 and 2017 with at least one CHD diagnosis in their medical records. The cumulative dose of ionizing radiation corresponding to cardiac diagnostic and therapeutic procedures was quantified considering a 6-month exposure lag. The recency-weighted cumulative exposure (WCE) model, a flexible extension of Cox’s proportional hazards model, was used to assess the association.Results:We identified 139,975 children with CHD born between 1999 and 2017 and followed them for 1,388,681 person-years since birth. In this population, 718 hematopoietic cancer cases were observed. Children with HC were exposed to low-dose ionizing radiation earlier in life (median age at first exposure: 6 vs. 10 months; p=0.03) and had more procedures than those without cancer (mean number of procedures: 0.4 vs. 0.2; p

Circulation, Volume 146, Issue Suppl_1, Page A15560-A15560, November 8, 2022. Aging and low aerobic capacity are associated with an increased risk of cardiovascular events and mortality. We reported that a polygenic rat model selectively bred for low aerobic capacity (LCR) showed aortic stiffness and dysfunction with age compared to rats bred for a high aerobic capacity (HCR). We observed increased aortic mitochondrial ROS and extracellular mtDNA DAMPs levels, activation of AIM2 inflammasome and its downstream effectors and increased collagen content in old LCR rat aortas. However, the molecular mechanisms linking low aerobic capacity to inflammation in aging have not been elucidated. In order to decipher the changes in genetic networks in low aerobic capacity and aging-associated aortic stiffness, a global transcriptome analysis was performed by RNA-Seq and gene ontology analysis of aortas from young (4 month) and old (27 month) LCR and HCR rats. Down-regulated pathways in old LCR aortas include mitochondrial biogenesis and mitophagy and up-regulated pathways include pro-inflammatory pathways, apoptosis/necroptosis/ferroptosis pathways, in contrast to HCR aortas which have higher levels of pathways regulating longevity, oxidative phosphorylation, and mitophagy and autophagy. In line with that, old LCR rats displayed a 54% reduction in mitophagy (colocalization of mitochondrial marker protein TOM20 with lysosomal marker protein LAMP1) in aortic media and a 76% reduction in cultured VSMCs in comparison to older HCR rats. Mitophagy levels did not differ significantly between young LCR and HCR rats. The autophagic vacuole formation rate was a 12-fold lower in old LCR than in old HCR aortic VSMCs, suggesting that impaired mitophagy may be responsible for accumulation of mtDNA-derived damage associated molecular patterns (mtDNA DAMPs). Treatment with various inducers of mitophagy (rapamycin, deferiprone, and MitoTEMPO) significantly increased mitophagy and decreased mtDNA DAMPs levels in old LCR VSMCs. This was also associated with a reduction in inflammasome activation, mitochondrial dysfunction, and ROS levels. We conclude that impaired mitophagy causes accumulation of DAMPs and inflammasome activation, inducing aortic stiffness and dysfunction in old age LCR rats.

Circulation, Volume 146, Issue Suppl_1, Page A14329-A14329, November 8, 2022. Background:Cardiac tamponade is a potentially fatal complication of catheter ablation for atrial fibrillation (AF). The risk of cardiac tamponade during AF ablation in underweight patients has never been investigated. This study aimed to evaluate the impact of body mass index (BMI) on the prediction of cardiac tamponade during AF ablation.Methods:Patients who underwent catheter ablation for AF between April 2016 and March 2018 were analyzed using a Japanese nationwide claims database, the Japanese Registry of All Cardiac and Vascular Diseases and the Diagnosis Procedure Combination (JROAD-DPC). Mixed-effects multivariable logistic regression analysis was performed to investigate the association between BMI and cardiac tamponade.Results:A total of 59,807 hospitalizations (median age: 67 [60-73], 29% women) with catheter ablation for AF were analyzed. Cardiac tamponade occurred in 657 patients (1.1%). Multivariable analysis revealed that being underweight (BMI

Circulation, Volume 146, Issue Suppl_1, Page A11108-A11108, November 8, 2022. Introduction:High-sensitivity cardiac troponin (hs-cTn) assays were first approved for use in the U.S. in 2017. They are the guideline preferred biomarker to evaluate patients with acute chest pain. Few data exist regarding implementation of hs-cTn assays in the U.S.Hypothesis:We hypothesize that use of hs-cTn assays has increased over time and that patients assessed with hs-cTn have a shorter length of stay (LOS) and similar use of cardiac testing.Methods:We examined trends in implementation of hs-cTn assays among participating hospitals in the NCDR Chest Pain MI Registry from 1/1/2019 through 9/30/2021. Excluding STEMI patients, associations between hs-cTn use, in-hospital diagnostic imaging, and patient outcomes were assessed using logistic or negative binomial regression models.Results:Among 550 participating hospitals with 251,000 patients in the registry, implementation of hs-cTn assays increased from 3.3% in Q1, 2019 to 32.6% in Q3, 2021 (Ptrend

Circulation, Volume 146, Issue Suppl_1, Page A11187-A11187, November 8, 2022. Introduction:The role of hypertriglyceridemia (HTG) in cardiovascular disease (CVD) remains controversial, especially in persons with well-controlled low-density lipoprotein cholesterol (LDL-C).Hypothesis:We aimed to evaluate the association between triglyceride (TG) levels and CVD mortality according to LDL-C and age in a general population.Methods:From the Korean National Health Insurance Service database, 15,672,028 participants aged 18-99 who underwent routine health examinations were followed up for CVD mortality. Hazard ratios (HRs) for CVD mortality were calculated using Cox models after adjusting for various confounders.Results:During a mean 8.8 years of follow-up, 105,174 individuals died from CVD. There was a clear log-linear association between TG and overall CVD mortality down to 50 mg/dL. Each two-fold increase in TG was associated with 1.10-fold (overall CVD), 1.22-fold (ischemic heart disease [IHD]), 1.24-fold (acute myocardial infarction [AMI]), and 1.10-fold (ischemic stroke) higher CVD mortality. Hemorrhagic stroke and heart failure were not associated with TG levels. The impact of HTG on CVD weakened but remained present in persons with LDL-C

Circulation, Volume 146, Issue Suppl_1, Page A12285-A12285, November 8, 2022. Background:Recent studies increase concern for embolic events during radiofrequency ablation (RFA) for ventricular arrhythmias (VA).Objective:To assess peri-procedural symptomatic embolic events and anticoagulation regimens in patients undergoing endocardial RFA for VA.Methods:All patients undergoing endocardial RFA for VA from October 2018 to September 2021 were prospectively assessed for complications in hospital before discharge and at 30 days by clinic visit or phone call. Anticoagulation regimens were at the discretion of the treating physician.Results:There were 663 procedures in 616 patients (age 62+4 yrs, 73% structural heart disease, 48% sustained VT). Prior to the procedure 464 patients (70%) were taking an antithrombotic agent, either a direct acting anticoagulant agent (DOAC), warfarin, aspirin (ASA), other antiplatelet agent, or combinations (table 1); and the same type of agent was continued after ablation in 462. Of the 199 patients not receiving antithrombotic agents pre-ablation, 82.4% received 325 mg of ASA daily after the procedure, 3.0% received lower dose ASA, and 16 were started on DOAC or warfarin. There were 59 complications (8.9%) in 53 procedures. There were 2 strokes (0.3%); there were no transient ischemic attacks or other embolic events. There were 25 (3.8%) bleeding complications including 14 due to vascular access (2.1%) and 11 pericardial effusions (1.6%). Bleeding complications were more frequent in patients on the combination of antiplatelet and DOAC pre- or post-procedure.Conclusions:In this large single center series most patients undergoing VA ablation were receiving antithrombotic therapy pre-procedure that was continued post procedure. Full dose ASA was the most common post-procedure regimen for those not on pre-procedure anticoagulation. Stroke and emboli appear very rare. Combined antiplatelet and DOAC therapy is associated with increased bleeding risk.

Circulation, Volume 146, Issue Suppl_1, Page A15388-A15388, November 8, 2022. Background:Patients with heart failure (HF) commonly remain symptomatic after medical treatment. Symptoms are associated with rehospitalizations and mortality. We developed a 6-month nutrition intervention targeting the 3 most common HF symptoms: edema, shortness of air, and fatigue. The intervention involves 3 nutrients that target the pathologic pathways underlying symptoms: sodium, omega-3 fatty acids, and lycopene.Hypothesis:Time to first event will be longer in the nutrition intervention group than in the placebo group at 1-year follow-up.Methods:This was a randomized controlled double-blind clinical trial where 118 patients (mean age 63±12 years; 40% female; 64% NYHA class III or IV) with HF were randomized to active intervention vs placebo groups. The active intervention included a skill-building strategy based on Theory of Planned Behavior using Motivational Interviewing. It included a low sodium (LS) diet (2500mg sodium/day), lycopene supplementation daily (8 ounces [oz] of LS sodium tomato juice or 11.5 oz of LS V8 juice), and omega-3 fatty acid capsules (350mg EPA, 50 mg DHA/capsule) 3/meal with each meal. Placebo patients received generic instructions to follow a LS diet, 8 oz/day of fruit juice with no lycopene (e.g. cranberry juice) and capsules that contained soybean oil, but that looked like intervention capsules. Cox proportional hazards modeling was done to determine time to event of cardiac hospitalization or death based on intervention group. Models were adjusted for age, gender, NYHA class and HF medications.Results:The two groups were similar at baseline. The active intervention group had better event-free survival (Figure, p = 0.03) independent of covariates. Placebo patients were 2.2 (95% CI 1.025 – 4.584) times more likely to experience an event.Conclusion:A diet-based intervention aimed at the pathologic pathways underlying the 3 most common HF symptoms is successful in reducing cardiac rehospitalizations and mortality.

Circulation, Volume 146, Issue Suppl_1, Page A15317-A15317, November 8, 2022. Case Presentation:A 42-year-old male with a past medical history of recurrent myopericarditis treated with a combination of NSAIDs, colchicine, and steroids presented for left-sided chest pain. The pain first recurred when he attempted a prednisone taper and he was started on Anakinra. Upon presentation, physical examination and laboratory findings were within normal limits. Echocardiography and electrocardiogram were within normal limits. Cardiac magnetic resonance imaging (CMR) showed transmural enhancement of the basal-mid inferolateral segments and patchy mid-myocardial enhancement in the basal-mid anterolateral segments. Nuclear medicine PET showed FDG uptake in the basal anteroseptal, anterolateral, inferolateral, inferior, and apical segments suggestive of active inflammation. Initially, the diagnosis was thought to be recurrent myopericarditis of unknown etiology. Subsequent right heart catheterization with endomyocardial biopsy (EMB) showed mononuclear infiltrates in the interstitium associated with myocyte infiltration and focal moderate interstitial fibrosis. Due to his clinical, imaging, and pathologic findings, he was diagnosed with lymphocytic myocarditis. His anti-inflammatory therapy regimen was reinstated, and he was started on Mycophenolate Mofetil. On follow-up, the patient had significant symptomatic improvement.Discussion:Lymphocytic myocarditis is a pattern of myocardial inflammation that is typically associated with autoimmune and idiopathic causes. Myocarditis frequently manifests with signs and symptoms of heart failure, including chest pain, dyspnea, and arrhythmias. Diagnosis of myocarditis is often supported by CMR and FDG-PET findings, however, EMB is the gold standard for the diagnosis of myocarditis. Treatment is generally supportive, though immunomodulatory therapies have gained increased popularity due to benefits in treating symptoms and preventing complications of heart failure.

Circulation, Volume 146, Issue Suppl_1, Page A14354-A14354, November 8, 2022. Background:Patients with heart failure (HF) are known to be stratified the risk of mortality by serum chloride level. However, since large-scaled studies to date have not included the elderly patients, it is still unclear whether serum chloride level well predicts the prognosis of the elderly patients with HF, whose clinical profiles are different from young adult patients. We aimed to test the hypothesis that hypochloremia gave different prognostic impacts in non-elderly and elderly patients with HF.Methods:This observational study included 1,326 elderly patients ( >65 year-old) without regular hemodialysis who were hospitalized for worsening of HF and discharged alive. They were divided into two subgroups depending on serum chloride levels at admission (Low-chloride group (98 mEq/L, n=1518)), referred to prior reports. Propensity scores were developed and patients in Normal-chloride group were matched with those in Low-chloride group in a 1:1 ratio. The endpoint of this study was death from any cause.Results:Among 1,326 unmatched patients, Low-chloride group included significantly more male patients, and those with higher BUN, CRP, bilirubin levels, dose of furosemide and atrial fibrillation, and prescriptions of oral anticoagulant, and lower BMI, blood pressure, hemoglobin, prescription of mineral corticoid receptor antagonist, thiazide and statins. Following propensity score matching by diverse baseline parameters, 106 pairs in both groups were included in the matched population. During 413 days of median observational period, 62 patients (28.8%) died. Kaplan-Meier analysis showed that patients in the Low-chloride group had a significantly higher mortality rate (p=0.011,Figure).Conclusion:In this observational study, baseline hypochloremia was associated with an increased mortality in elderly patients hospitalized with heart failure.

Circulation, Volume 146, Issue Suppl_1, Page A11270-A11270, November 8, 2022. Introduction:Sodium-glucose co-transporter2 inhibitors (SGLT2i) showed benefit in major cardiovascular diseases characterized by low-grade inflammation. However, the role and function of SGLT2 in the heart remain unclear.Hypothesis:This study evaluated whether SGLT1/2 are expressed in the heart of patients with cardiac diseases, and determined the role of low-grade inflammation and the functional consequences.Methods:Human left ventricle (LV) biopsies were collected from 17 patients with aortic and mitral valves stenosis or hypertrophic cardiomyopathy at Strasbourg Hospital. Cultured endothelial cells (EC) were from pig coronary arteries. Expression levels were assessed by RT-qPCR, Western blot analysis and immunofluorescence staining, and the level of oxidative stress and nitric oxide (NO) using fluorescent probes.Results:SGLT1/2 protein levels were observed in the LV of cardiac patients and correlated p-p65 NFκB levels. SGLT2, VCAM-1 and TNF-α staining was observed in the endothelium of coronary microvessels and, to some extent, cardiomyocytes. TNF-α upregulated SGLT1 and 2, VCAM-1, AT1R and ACE expression and decreased that of eNOS and the bradykinin-stimulated NO formation in EC. The stimulatory effect of TNF-α was inhibited by an NF-kB inhibitor and SGLT2 siRNA but not by SGLT1 siRNA. Oxidative stress in LV sections and TNF-α-treated EC was inhibited by VAS-2870 (NADPH oxidase inhibitor), losartan (AT1R antagonist) and empagliflozin (SGLT2i), and in LV by infliximab (TNF-α receptor inhibitor).Conclusions:The findings indicate that SGLT2 is expressed in the LV of cardiac patients in the coronary endothelium and cardiomyocytes, and associated with their low-grade inflammatory status. Moreover, TNF-α upregulated the AT1R/NAPDH oxidase/SGLT2 crosstalk to sustain oxidative stress promoting endothelial dysfunction. Thus, SGLT2 appears as an interesting target to protect the coronary microcirculation.

Circulation, Volume 146, Issue Suppl_1, Page A13660-A13660, November 8, 2022. Introduction:The Tsimane forager-horticulturalists of Bolivia are highly physically active, carry high infectious disease burdens, and have the lowest reported population levels of coronary artery calcium (CAC), as well as relatively low cholesterol (LDL, HDL, total) levels. In industrialized populations, lipoprotein(a)—Lp(a)— is strongly predictive of coronary artery and aortic valve calcification (AVC). However, these relationships have not been assessed in this non-urban population.Hypothesis:We hypothesize that, despite the very low levels of CAC seen in the Tsimane, Lp(a) is higher in those with CAC and AVC but overall lower in Tsimane compared to a US comparator population (CARDIA).Methods:CAC and AVC were measured by non-contrast cardiac CT in 917 Tsimane (15.5% CAC positive, 21.0% AVC positive). A subset of 98 Individuals with and without CAC or AVC had serum Lp(a) analyzed (median age 63 yrs, range 41-91 yrs, 67% male) using a standard double monoclonal antibody ELISA at the Northwest Lipid Metabolism and Diabetes Research Laboratory (University of Washington). Individuals with CAC and AVC were oversampled (45.9% CAC positive, and 76.7% with AVC; 10% with neither) to ensure statistical power.Results:Overall, Tsimane had significantly lower levels of Lp(a) than CARDIA white males (Tsimane male median 16.5 nmol/L vs US median 19.4 nmol/L; p

Circulation, Volume 146, Issue Suppl_1, Page A14056-A14056, November 8, 2022. Introduction:Isolated very low QRS voltage (VLV; ≤ 0.3mV) on frontal leads on the electrocardiogram (ECG) has been shown to predict recurrence of neurally mediated syncope (NMS). In most patients VLV occurs in only one isolated ECG lead, however a small number of patients have ≥ 2 leads with VLV (Figure A), the significance of this pattern being unknown.Hypothesis:The aim of the study was to explore the potential relationship between the number of frontal leads with VLV and NMS recurrence.Methods:We included 268 patients with NMS (age 48±20 years, 150 women), with a median of 3 syncopal episodes who were followed for a median of 12 months.Results:Very low voltage was present in one frontal lead in 98 patients (37%), in 2 leads in 16 patients (6%), and in 3 leads in 1 patient (0.4%). Patients with VLV in multiple frontal leads had significantly smaller left ventricular end diastolic diameter (LVEDD) and left ventricular systolic diameter (LVESD) than patients with no VLV (42.8±3.9mm vs. 45.6±5.2mm; p = 0.029, and 27.7±3.9mm vs. 30.3±5.0mm; p = 0.049, respectively). During follow-up 69 patients (26%) experienced recurrent syncope. The actuarial total syncope recurrence rate increased progressively with the number of frontal leads displaying VLV (log rank test chi2=34.78; p < 0.0001; Figure B). Multiple frontal leads with VLV was associated with a relative risk of syncope recurrence of 5.5 in univariate analysis. Multivariate Cox regression revealed that the number of frontal leads displaying VLV predicted recurrent syncope (HR 1.83, 95%CI 1.28-2.62) in a model that included history of presyncope and syncope (HR 3.43, 95%CI 1.77-6.65) and LVEDD (HR 0.94, 95%CI 0.89-0.99).Conclusions:Very low voltage in multiple frontal leads is rare. If this pattern occurs, it is associated with a high risk of recurrent NMS. This phenomenon, which appears to be related at least partially to a smaller LV cavity size, may help generate new diagnostic tools and insights into the pathogenesis of NMS.

Circulation, Volume 146, Issue Suppl_1, Page A13076-A13076, November 8, 2022. Introduction:Mitochondrial respiration defects accompanied by low nitric oxide (NO) are associated with heart failure in congenital heart disease (CHD) patients with hypoplastic left heart syndrome (HLHS). Here we investigated the genetic etiology of low NO in patients with CHD.Hypothesis:Mutations in mitochondrial-related genes involved in NO metabolism contributes to the low NO associated risk for heart failure and need for heart transplantation in HLHS.Methods and Results:We performed a case-control association study among 588 white CHD cases including 41 with HLHS, and 24,143 white controls from the genome aggregation database (gnomAD). A rare conserved stopgain variant (rs562886845) inSLC25A2encoding mitochondrial ornithine transporter was significantly enriched among the HLHS patients with poor clinical outcome (Group II, Table 1), with 15.8% carrying this mutation, yielding odds ratio of 17.07 (p= 5.23 х 10-4) in comparison to CHD patients without left ventricular outflow tract obstruction or 7.63 (p=2.68 х 10–3) in comparison to gnomAD control cohort. Significantly,SLC25A2is the only mitochondrial transporter exporting asymmetric dimethylarginine, a natural NO synthase inhibitor. The three HLHS patients with thisSLC25A2variant showed very low nasal NO (nNO), a proxy for endogenous NO production capacity. All three patients had received heart transplant, with two being heterozygous and one homozygous for this variant. Significantly, the HLHS patient with the homozygous mutation had nNO at background levels (2.8 nl/min at 7 years of age as compared to >200 nl/min expected nNO).Conclusions:Our findings uncovered an essential role forSLC25A2in determining NO production capacity in patients with HLHS. As all three HLHS patients with this variant and very low nNO survived with heart transplant, this variant should be further investigated as a genetic marker for predicting the need for early heart transplant in HLHS.

Circulation, Volume 146, Issue Suppl_1, Page A11036-A11036, November 8, 2022. Introduction:Aortic Valve Calcification (AVC) measured by computed tomography (C-CT) and Dobutamine stress echocardiography (DSE) are both important when determining AS severity in low flow low gradient (LFLG) AS. It is generally accepted that AS is moderate if aortic mean gradient is

Circulation, Volume 146, Issue Suppl_1, Page A14221-A14221, November 8, 2022. Introduction:Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure. Novel therapies for transthyretin (TTR) CA elevate the need for early identification when treatment has the greatest efficacy. The TTR CA score (TCAS) was recently developed to predict the likelihood of TTR CA in patients undergoing 99mTc-pyrophosphate scintigraphy (PYP) scanning. Its simple inputs could be easily extracted from the electronic health record (EHR), suggesting possible use as a quick, EHR-based screening tool. We perform the first external validation of the TCAS using only EHR-extracted data. We hypothesized that a screening algorithm like TCAS could be generalizable and feasible to implement using our EHR.Methods:EHR data were extracted on all patients at a large academic medical center who underwent PYP scans between 2017 and 2022. PYP scan was considered positive if the patient was part of our institution’s registry of patients with confirmed CA. Inputs – age, sex, echocardiogram wall thickness and ejection fraction, and hypertension diagnosis codes – were converted to TCAS scores. Area under the receiver operating characteristic curve (AUROC) was calculated to analyze predictive performance. Using a TCAS ≥6 as the threshold for high-risk, performance characteristics were calculated.Results:Of 365 patients who underwent PYP scan, 335 had sufficient records to calculate a TCAS. Of these 335 patients, 69 (20.6%) had positive PYP scans. Median TCAS was 5 (interquartile range 4,7). The AUROC was 0.826, with a sensitivity of 87.0%, specificity of 63.9%, positive predictive value of 38.5%, and negative predictive value (NPV) of 95.0%.Conclusions:External validation of the TCAS supports its strong predictive performance with comparable AUROCs to the initial study (0.84-0.89). Clinically, with its high NPV, the TCAS has potential to serve as a simple, low-cost screen to avoid costly PYP scans. We demonstrate the ability to extract all inputs from the EHR, without need for manual chart review or calculation, suggesting that the TCAS could function as an EHR-based screening tool. Low-cost screening tools are needed to identify patients who would benefit from TTR CA workup with PYP scanning, facilitating treatment at earlier disease stages.