Risultati per: LBP (Low Back Pain): Cosa dicono le linee guida del mal di schiena

Circulation, Volume 146, Issue Suppl_1, Page A14149-A14149, November 8, 2022. Introduction:High power radiofrequency ablation (RFA), a novel technique, is recently being employed for pulmonary vein isolation (PVI) for atrial fibrillation (AF). This study aimed to report our center’s procedural data and preliminary results of a high power RFA technique for AF without fluoroscopic guidance.Methods:Symptomatic AF patients were consecutively enrolled in this prospective observational study and underwent PVI. Ablation index (AI) was marginally used for at least 400 on the posterior wall and 500 on the anterior wall or 15 seconds total at 50 Watt ablation power, whichever came first. Contact-force catheter and esophageal temperature was used during the procedure. Post-ablation esophageal endoscopy was utilized. PVI was performed using CARTO and the ST SF D/F curve ablation catheter in a temperature-controlled mode.Results:PVI was achieved in all (n = 36, mean age: 68±11.3 years, female: 29%, CHADsVASc: 2.8±1.5, LA volume index:60.4±17.2 mL/m2). 29(80%) patients had paroxysmal AF. For left wide antral circumferential ablation (WACA); total duration was 7.4±11.3 min, total ablation sites were 49.9±11.2, average contact force was 9.97±2.2 g and average AI was 363.9±20.5. For right WACA total duration was 6.4±2 min, total ablation sites were 45.6±15.3, average contact force was 13.0±3.5 g and average AI was 403.6±32.9. WACA technique was employed for paroxysmal AF, additional ablation lines were targeted for persistent AF. For the entire flouro-less, 50W study population, average AI was 382.2±26.6, total ablation duration was 18.1±4.7 min, total ablation sessions were 118.4±33.4 and average temperature was 38.7±1.4 degree Celsius. During in-hospital follow-up no major complications such as death, stroke, tamponade, or atrio-esophageal fistula occurred.Conclusions:50 watts fluoro-less AF RFA is a safe and efficient procedure.

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 A13039-A13039, November 8, 2022. Background:The incidence of anomalous aortic origin of the right coronary artery (AAORCA) is between 0.026% and 0.25%. There is limited data regarding medical versus surgical management. We present a case of AAORCA which did not “qualify” for surgical intervention but remained symptomatic on medical management.Presentation:A 58-year-old female with paroxysmal atrial fibrillation presented for the eighth time in the past two years with recurrent atypical chest pain and lightheadedness. Vital signs and cardiac biomarkers were normal.Work-up:EKG showed normal sinus rhythm. TTE revealed EF 68%. Myocardial perfusion imaging was normal but exercise stress test showed ventricular ectopy, ventricular bigeminy, short bursts of ventricular tachycardia (VT) at peak exercise, and a 7-beat run of VT. A 30-day event monitor revealed a 17-beat run of VT at a rate of 173 bpm (Figure A).Management:Cardiac catheterization showed the dominant right coronary artery (RCA) arising from the left coronary cusp with a shared ostium to the left coronary system (Figure B-D). A coronary CT scan confirmed dominant RCA arising from left coronary cusp (Figure E) with an interarterial course (Figure F) and slit-like appearance of the proximal RCA, with a likely intramural course (Figure G).She was managed conservatively with restriction of vigorous exercise, up-titration of beta-blockers, addition of anti-anginal agents and implantation of loop recorder.Conclusion:The most updated consensus statement for AAORCA recommends surgical intervention for those with signs or symptoms of myocardial ischemia (true angina, findings on provocative testing, aborted sudden cardiac arrest or non-vagally-mediated arrhythmia).Although our patient did not “qualify” for surgical intervention, she continued to experience refractory symptoms. Hence, it is of utmost importance to consider surgical intervention in patients who have failed medical management, for improved quality of life.

Circulation, Volume 146, Issue Suppl_1, Page A11162-A11162, November 8, 2022. Background:Blood stasis is one of the important pathogeneses in the formation of left atrial (LA) thrombi. The LA appendage peak flow velocity (LAAV) is an established quantitative parameter for estimating the thromboembolic risk. However, it remains unknown whether the LAAV affects the successful resolution of LA thrombi even after prescribing an appropriate oral-anticoagulation treatment.Purpose:To evaluate whether the LAAV is associated with successful resolution of LA thrombi.Methods:The analysis was performed from the LAT trial, a multicenter observational study investigating the outcomes of silent LA thrombi detected by trans-esophageal echocardiography (TEE) or computed tomography. Management of oral anticoagulants was at the physician’s discretion, and resolution of LA thrombi was checked by follow-up TEE. Of 297 patients registered in the trial, we enrolled 236 patients (median age, 69 years; 28% female; 100% atrial fibrillation) whose baseline LAAV data was available in this study.Results:The prescription rates of oral-anticoagulants at baseline and the final follow-up were 83.5% and 93.6%, respectively (p = 0.002). During a median follow-up of 387 (interquartile range, 367-414) days after the thrombi detection, LA thrombi successfully resolved in 145 (61.4%) patients by altering the oral anticoagulants. Patients with resolved LA thrombi had a higher baseline LAAV than those without (28.4 ± 18.5 vs. 19.8 ± 9.3 cm/s, p < 0.001). A receiver operating curve analysis revealed that the best cut-off value for predicting treatment success or failure was 25 cm/s (area under the curve: 0.651, p < 0.001). After adjusting for age, gender, body mass index, heart failure, and warfarin use, an LAAV ≤ 25 cm/s was a significant predictor of failed resolution of LA thrombi (hazard ratio, 1.54; 95% confidence interval, 1.09-2.18; p = 0.015).Conclusions:In the LAT trial, one third of patients failed thrombolysis even 1 year after identifying silent LA thrombi. An LAAV ≤ 25 cm/s at baseline independently predicted treatment failure with oral anticoagulants.

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 A12333-A12333, November 8, 2022. Introduction:There are many reports on the effects of on-treatment platelet reactivity using P2Y12reaction units (PRU) on the ischemic or bleeding risk in patients who underwent percutaneous coronary intervention (PCI). However, there was little report including low-dose prasugrel (2.5mg).Hypothesis:We assumed that low-dose prasugrel use may contribute to the effectiveness and safety in the chronic phase of PCI in Japanese patients.Methods:This prospective observational study included 398 patients who underwent PCI between 2017 and 2018 (mean age: 68±11 years, male: 83%). Serial PRU measurements were performed; the baseline was at 6 to 12 months after PCI, and the follow-up was after 6 months later. The PRU was measured by the VerifyNow® P2Y12assay, and we assessed the distribution of PRU in each P2Y12inhibitor, after defined PRU 86 to 238 as therapeutic window.Results:Among 398 patients, the follow-up PRU was obtained in 360 patients (90%), and 80 patients (22%) were taking prasugrel 2.5mg. The baseline PRUs of clopidogrel 75mg, prasugrel 3.75mg, and prasugrel 2.5mg were 175±64, 147±55, and 154±66, respectively (p

Circulation, Volume 146, Issue Suppl_1, Page A11952-A11952, November 8, 2022. Introduction:Around 80% of patients with atherosclerotic cardiovascular disease (ASCVD) do not achieve adequate reduction of low-density lipoprotein cholesterol (LDL-C) in current clinical practice, especially among patients on statin monotherapy. Greater understanding of attributes favored by prescribing physicians may improve treatment outcomes.Methods:To understand attributes of putative statin ‘add-on’ LDL-C lowering therapies, we conducted a discrete choice experiment survey of 200 U.S. cardiologists and 50 primary care physicians (PCPs). The survey presented a series of discrete choices to respondents, systematically varied across 8 treatment attributes: % LDL-C reduction, myalgias, other side effects, route and frequency of administration, time to prior authorization, patient out-of-pocket cost (OOPC) and adherence. Data were analyzed using logistic regression with clustering and heterogeneity adjustments to estimate preference weights for each attribute.Results:Both cardiologists and PCPs most valued efficacy in LDL-C reduction, with odds ratio (OR) for treatment preference of 1.69 per additional 10% reduction in LDL-C, and minimization of monthly OOPC with OR of 0.90 per $10 increase. Cardiologists preferred injectable therapies, with 57.5% of respondents preferring a drug with attributes of a small interfering RNA (siRNA) injectable and 16.4% preferring attributes of a proprotein convertase subtilisin kexin type 9 inhibitor (PCSK9i) biologic over oral ezetimibe therapy, as compared to only 2.8% preference for siRNA injectable among PCPs vs. oral therapy. Across all respondents, preference for injectables was higher for patients with history of nonadherence, with 55.7% preferring a drug with health-care practitioner-based injection every 6 months and 25.4% preferring a drug with properties of monoclonal antibody-based home injections once or twice monthly.Conclusions:Results indicate LDL-C lowering efficacy is a primary driver of physician prescribing preferences, with PCPs placing increasing consideration on OOPC. For patients with suboptimal adherence – the majority of those seen in clinical practice – U.S. physicians are more likely to prefer less-frequent injectable to oral therapies.

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.

Circulation, Volume 146, Issue Suppl_1, Page A10484-A10484, November 8, 2022. Introduction:Carotid plaque is recommended for cardiac risk stratification for intermediate risk patients but has not been integrated into cardiology community clinics to help refine testing and reduce risk for major adverse cardiovascular events (MACE). The purpose was to determine the clinical usefulness of carotid plaque score (PS) to guide management of low-intermediate risk patients.Methods:Patients 40-75 years who received a carotid ultrasound were followed up to 10 years for MACE (cardiovascular death, myocardial infarction, stroke). Low-intermediate risk participants (n = 9,114) with no known cardiovascular disease were included. Administrative data holdings housed at IC/ES were used for event follow-up. Kaplan-Meier curves and Cox proportional hazard ratios determined relative risk. Combining plaque score (Rotterdam method, plaque presence within carotid segments, PS 0 to 6) with stress echo (SE) was assessed in a subset of participants (n = 624).Results:The optimum threshold for PS = 2 for 1-year MACE (AUC = 0.738). The population rate of MACE over 10 years was 4%. In participants referred for SE, PS of

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 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 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 A13079-A13079, November 8, 2022. Introduction:Glycosylated apolipoprotein J (ApoJ-Glyc) has been suggested to be a marker for the early detection of myocardial ischemia. Ischemia induces an intracellular accumulation of non-glycosylated ApoJ that mirrors a reduction in ApoJ-Glyc serum concentration in acute ischemic syndromes.Objective:The EDICA clinical trial – multi-centre, international, diagnostic study (NCT04119882)- was carried out to assess the performance of ApoJ-Glyc as a biomarker for the early detection of myocardial ischemia in patients attending the A&E department with chest pain suggestive of acute coronary syndrome (ACS).Methods:EDICA assessed 404 patients. Blood samples were obtained on admission, for assessment of high sensitivity-troponin (hs-Tn) and ApoJ-Glyc. ApoJ-Glyc serum levels were analyzed with a novel ELISA, targeting a specific glycosylated variant of ApoJ (ApoJ-GlycA6).Results:Based on clinical diagnostic tests, 291 patients were given a final diagnosis of “non-ischemic” event and 113 patients were considered to have had an ischemic event (33 STEMI, 48 NSTEMI, 27 Unstable Angina and 5 “unclassifiable” ACS). ApoJ-GlycA6 levels were significantly lower on admission in ischemic patients, compared with non-ischemic patients (66 [46-90]vs.73 [56-95] μg/ml, respectively; P=0.04). Ischemic patients who underwent PCI and had a pre-PCI TIMI 0-2 flow showed significantly lower ApoJ-GlycA6 levels at admission compared with non-ischemic patients (64 [37-81]vs.73 [56-95] μg/ml; P=0.01). Of interest, 51% of ischemic patients, had “inconclusive” or negative hs-Tn at admission. Among these, ApoJ-GlycA6 identified the ischemic event in 48% (

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 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.