Comprehensive clinical and genetic analyses of circulating bile acids and their associations with diabetes and its indices.

Bile acids (BAs) are cholesterol-derived compounds that regulate glucose, lipid, and energy metabolism. Despite their significance in glucose homeostasis, the association between specific BA molecular species and their synthetic pathways with diabetes mellitus (DM) is unclear. Here, we used a recently validated stable-isotope dilution highperformance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to quantify a panel of BAs in fasting plasma from subjects (n=2,145) and explored structural and genetic determinants of BAs linked to DM, insulin resistance and obesity. Multiple 12α-hydroxylated BAs were associated with DM [adjusted odds ratios (aORs):1.3-1.9 (all P<0.05)] and insulin resistance [aORs:1.3-2.2 (all P<0.05)]. Conversely, multiple 6a-hydroxylated BAs and isolithocholic acid (Iso-LCA) were inversely associated with DM and obesity [aORs:0.3-0.9 (all P<0.05)]. Genome-wide association studies (GWAS) revealed multiple genome-wide significant loci linked with nine of the 14 DM-associated BAs, including a locus for Iso-LCA (rs11866815). Mendelian randomization analyses showed genetically elevated DCA levels were causally associated with higher BMI, and Iso-LCA levels were causally associated with reduced BMI and DM risk. In conclusion, comprehensive large-scale quantitative mass spectrometry and genetics analyses show circulating levels of multiple structurally specific BAs, especially DCA and Iso-LCA, are clinically associated with and genetically linked to obesity and DM.

Trimethylamine-N-Oxide and Related Metabolites: Assessing Cardiovascular Risk in the Dallas Heart Study.

OBJECTIVE: To evaluate the association between trimethylamine N-oxide (TMAO) and related metabolites with adverse cardiovascular events in a multiethnic urban primary prevention population. METHODS: We performed a case-control study of 361 participants of the Dallas Heart Study, including 88 participants with an incident atherosclerotic cardiovascular disease (ASCVD) event and 273 controls matched for age, sex, and body mass index without an ASCVD event during 12 years of follow-up (January 1, 2000, through December 31, 2015). Plasma levels of TMAO, choline, carnitine, betaine, and butyrobetaine were measured by mass spectrometry. The differential odds for incident ASCVD by metabolite levels between cases and controls were compared by a conditional logistic regression model adjusted for cardiovascular risk factors. RESULTS: Participants with incident ASCVD had higher levels of TMAO and related metabolites compared with those without ASCVD (P<.05 for all). Those with plasma TMAO concentrations in quartile 4 had a more than 2-fold higher odds of ASCVD compared with those in quartile 1 (odds ratio, 2.77 [95% CI, 1.05 to 7.7; P=.04] for hard ASCVD and 2.41 [95% CI, 1.049 to 5.709; P=.04]). Similar trends were seen with the related metabolites choline, betaine, carnitine, and butyrobetaine. CONCLUSION: Our results suggest that TMAO and related metabolites are independently associated with ASCVD events. Although further studies are needed, measurement of TMAO and related metabolites may have a role in ASCVD risk stratification for primary prevention.

Cardiac MRI-Enriched Phenomapping Classification and Differential Treatment Outcomes in Patients With Ischemic Cardiomyopathy.

BACKGROUND: Significant controversy continues to confound patient selection and referral for revascularization and mitral valve intervention in patients with ischemic cardiomyopathy (ICM). Cardiac magnetic resonance (CMR) enables comprehensive phenotyping with gold-standard tissue characterization and volumetric/functional measures. Therefore, we sought to determine the impact of CMR-enriched phenomapping patients with ICM to identify differential outcomes following surgical revascularization and surgical mitral valve intervention (sMVi). METHODS: Consecutive patients with ICM referred for CMR between 2002 and 2017 were evaluated. Latent class analysis was performed to identify phenotypes enriched by comprehensive CMR assessment. The primary end point was death, heart transplant, or left ventricular assist device implantation. A multivariable Cox survival model was developed to determine the association of phenogroups with overall survival. Subgroup analysis was performed to assess the presence of differential response to post-magnetic resonance imaging procedural interventions. RESULTS: A total of 787 patients were evaluated (63.0±11.2 years, 24.8% women), with 464 primary events. Subsequent surgical revascularization and sMVi occurred in 380 (48.3%) and 157 (19.9%) patients, respectively. Latent class analysis identified 3 distinct clusters of patients, which demonstrated significant differences in overall outcome (P<0.001). Latent class analysis identified differential survival benefit of revascularization in patients as well as patients who underwent revascularization with sMVi, based on phenogroup classification, with phenogroup 3 deriving the most survival benefit from revascularization and revascularization with sMVi (hazard ratio, 0.61 [0.43-0.88]; P=0.0081). CONCLUSIONS: CMR-enriched unsupervised phenomapping identified distinct phenogroups, which were associated with significant differential survival benefit following surgical revascularization and sMVi in patients with ICM. Phenomapping provides a novel approach for patient selection, which may enable personalized therapeutic decision-making for patients with ICM.

Impact of baseline kidney dysfunction on oral diuretic efficacy following hospitalization for heart failure - insights from TRANSFORM-HF.

AIM: Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all-cause mortality or hospitalization. Clinicians have traditionally favoured torsemide in the setting of kidney dysfunction due to better oral bioavailability and longer half-life, but direct supportive evidence is lacking. METHODS AND RESULTS: The TRANSFORM-HF trial randomized patients hospitalized for HF to a long-term strategy of torsemide versus furosemide, and enrolled patients across the spectrum of renal function (without dialysis). In this post-hoc analysis, baseline renal function during the index hospitalization was assessed as categories of estimated glomerular filtration rate (eGFR; <30, 30-<60, ≥60 ml/min/1.73 m2). The interaction between baseline renal function and treatment effect of torsemide versus furosemide was assessed with respect to mortality and hospitalization outcomes, and the change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS). Of 2859 patients randomized, 336 (11.8%) had eGFR <30 ml/min/1.73 m2, 1138 (39.8%) had eGFR 30-<60 ml/min/1.73 m2, and 1385 (48.4%) had eGFR ≥60 ml/min/1.73 m2. Baseline eGFR did not modify treatment effects of torsemide versus furosemide on all adverse clinical outcomes including individual components or composites of all-cause mortality and all-cause (re)-hospitalizations, both when assessing eGFR categorically or continuously (p-value for interaction all >0.108). Similarly, no treatment effect modification by eGFR was found for the change in KCCQ-CSS (p-value for interaction all >0.052) when assessing eGFR categorically or continuously. CONCLUSION: Among patients discharged after hospitalization for HF, there was no significant difference in clinical and patient-reported outcomes between torsemide and furosemide, irrespective of renal function.

Statins Do Not Significantly Affect Oxidative Nitrosative Stress Biomarkers in the PREVENT Randomized Clinical Trial.

PURPOSE: Preventing Anthracycline Cardiovascular Toxicity with Statins (PREVENT) (NCT01988571) randomized breast cancer or lymphoma patients receiving anthracyclines to atorvastatin 40 mg daily or placebo. We evaluated the effects of atorvastatin on oxidative and nitrosative stress biomarkers, and explored whether these biomarkers could explain the lack of effect of atorvastatin on LVEF in PREVENT. PATIENTS AND METHODS: Blood samples were collected and cardiac magnetic resonance imaging was performed prior to doxorubicin initiation and at 6 and 24 months. Thirteen biomarkers (arginine-nitric oxide metabolites, paraoxonase-1 [PON-1] activity, and myeloperoxidase) were measured. Dimensionality reduction using principal component analysis was used to define biomarker clusters. Linear mixed-effects models determined the changes in biomarkers over time according to treatment group. Mediation analysis determined if biomarker clusters explained the lack of effect of atorvastatin on LVEF. RESULTS: Among 202 participants with available biomarkers, median age was 53 years; 86.6% had breast cancer; median LVEF was 62%. Cluster 1 levels, reflecting arginine methylation metabolites, were lower over time with atorvastatin, although this was not statistically significant (p=0.081); cluster 2 levels, reflecting PON-1 activity, were significantly lower with atorvastatin (p=0.024). There were no significant changes in other biomarker clusters (p>0.05). Biomarker clusters did not mediate an effect of atorvastatin on LVEF (p>0.05) Conclusions: Atorvastatin demonstrated very modest effects on oxidative/nitrosative stress biomarkers in this low cardiovascular risk population. Our findings provide potential mechanistic insight into the lack of effect of atorvastatin on LVEF in the PREVENT trial.

Randomized Trial of a Selective Aldose Reductase Inhibitor in Patients With Diabetic Cardiomyopathy.

BACKGROUND: Progression to symptomatic heart failure is a complication of type 2 diabetes; heart failure onset in this setting is commonly preceded by deterioration in exercise capacity. OBJECTIVES: The study sought to determine whether AT-001, a highly selective aldose reductase inhibitor, can stabilize exercise capacity among individuals with diabetic cardiomyopathy (DbCM) and reduced peak oxygen uptake (Vo2). METHODS: A total of 691 individuals with DbCM meeting inclusion and exclusion criteria were randomized to receive placebo or ascending doses of AT-001 twice daily. Stratification at inclusion included region of enrollment, cardiopulmonary exercise test results, and use of sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists. The primary endpoint was proportional change in peak Vo2 from baseline to 15 months. Subgroup analyses included measures of disease severity and stratification variables. RESULTS: The mean age was 67.5 ± 7.2 years, and 50.4% of participants were women. By 15 months, peak Vo2 fell in the placebo-treated patients by -0.31 mL/kg/min (P = 0.005 compared to baseline), whereas in those receiving high-dose AT-001, peak Vo2 fell by -0.01 mL/kg/min (P = 0.21); the difference in peak Vo2 between placebo and high-dose AT-001 was 0.30 (P = 0.19). In prespecified subgroup analyses among those not receiving sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists at baseline, the difference between peak Vo2 in placebo vs high-dose AT-001 at 15 months was 0.62 mL/kg/min (P = 0.04; interaction P = 0.10). CONCLUSIONS: Among individuals with DbCM and impaired exercise capacity, treatment with AT-001 for 15 months did not result in significantly better exercise capacity compared with placebo. (Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy [ARISE-HF]; NCT04083339).

[A randomized controlled trial on the effect of early eschar dermabrasion combined with antimicrobial soft silicone foam dressing in the treatment of deep partial-thickness burn wounds in children].

Objective: To explore the effect of early eschar dermabrasion combined with antimicrobial soft silicone foam dressing (hereinafter referred to as foam dressing) in treating the deep partial-thickness burn wounds in children. Methods: This study was a randomized controlled trial. From June 2021 to December 2022, 78 pediatric patients with deep partial-thickness burns who met the inclusion criteria were admitted to the Department of Burns in Guiyang Steel Plant Employees Hospital. According to the random number table, the pediatric patients were divided into two groups, with 38 cases left in combined treatment group (with 20 males and 18 females, aged 26.00 (16.75, 39.75) months) and 39 cases in foam dressing group (with 21 males and 18 females, aged 19.00 (14.00, 31.00) months) after the exclusion of one dropped-out child in follow-up. The pediatric patients in combined treatment group underwent eschar dermabrasion of the wound within 48 hours after injury, the wound was covered with foam dressing after operation, and the dressing was replaced once every 7 days; for the pediatric patients in foam dressing group, the wound was sterilized within 48 hours after injury and covered with foam dressing, and the dressing was replaced once every 2 to 3 days. After the wound healing, the children in both groups were routinely applied with silicone gel twice a day for 3 weeks before started wearing elastic sleeves for more than 18 hours a day, and continuously for over than 6 months. The degree of pain during dressing change was evaluated using the children's pain behavior inventory FLACC. The adverse reactions during the treatment period, number of dressing changes, and wound healing time were observed and recorded. Six months after wound healing, the Vancouver scar scale (VSS) was used to evaluate the condition of the wound scar. Results: When changing dressing, the FLACC score for pain of pediatric patients in combined treatment group was 3.5 (2.0, 5.0), which was significantly lower than 6.0 (5.0, 8.0) in foam dressing group (Z=-5.40, P<0.05). During the treatment period, no adverse reactions such as wound edema, fluid accumulation, or peripheral skin rash allergies occurred in any pediatric patient in both groups. The number of dressing changes of pediatric patients in combined treatment group was 3 (3, 4) times, which was significantly less than 8 (7, 10) times in foam dressing group (Z=-7.58, P<0.05). The wound healing time of pediatric patients in combined treatment group was (19±5) days, which was significantly shorter than (25±6) days in foam dressing group (t=-4.48, P<0.05). Six months after wound healing, the VSS score for scar of pediatric patients in combined treatment group was 5 (2, 8), which was significantly lower than 7 (5, 10) in foam dressing group (Z=-3.05, P<0.05). Conclusions: Compared with using foam dressings alone, early eschar dermabrasion combined with foam dressings can reduce the number of dressing changes, alleviate the pain during dressing changes, and shorten the wound healing time in treating children with deep partial-thickness burns, and effectively alleviate scar hyperplasia by combining with anti-scar treatment post burns.

Non-Coding Ribonucleic Acids as Diagnostic and Therapeutic Targets in Cardiac Fibrosis.

PURPOSE OF REVIEW: Cardiac fibrosis is a crucial juncture following cardiac injury and a precursor for many clinical heart disease manifestations. Epigenetic modulators, particularly non-coding RNAs (ncRNAs), are gaining prominence as diagnostic and therapeutic tools. RECENT FINDINGS: miRNAs are short linear RNA molecules involved in post-transcriptional regulation; lncRNAs and circRNAs are RNA sequences greater than 200 nucleotides that also play roles in regulating gene expression through a variety of mechanisms including miRNA sponging, direct interaction with mRNA, providing protein scaffolding, and encoding their own products. NcRNAs have the capacity to regulate one another and form sophisticated regulatory networks. The individual roles and disease relevance of miRNAs, lncRNAs, and circRNAs to cardiac fibrosis have been increasingly well described, though the complexity of their interrelationships, regulatory dynamics, and context-specific roles needs further elucidation. This review provides an overview of select ncRNAs relevant in cardiac fibrosis as a surrogate for many cardiac disease states with a focus on crosstalk and regulatory networks, variable actions among different disease states, and the clinical implications thereof. Further, the clinical feasibility of diagnostic and therapeutic applications as well as the strategies underway to advance ncRNA theranostics is explored.

Hemodynamic Determinants of Cardiac Surgery-Associated Acute Kidney Injury.

OBJECTIVES: Examine the: 1) relative role of hemodynamic determinants of acute kidney injury (AKI) obtained in the immediate postcardiac surgery setting compared with established risk factors, 2) their predictive value, and 3) extent mediation via central venous pressure (CVP) and mean arterial pressure (MAP). DESIGN: Retrospective observational study. The main outcome of the study was moderate to severe AKI, per kidney disease: improving global outcomes, within 14 days of surgery. SETTING: U.S. academic medical center. PATIENTS: Adult patients undergoing cardiac surgery between January 2000 and December 2019 (n = 40,426) in a single U.S.-based medical center. Pulmonary artery catheter measurements were performed at a median of 102 minutes (11, 132) following cardiopulmonary bypass discontinuation. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The median age of the cohort was 67 years (58, 75), and 33% were female; 70% had chronic hypertension, 29% had congestive heart failure, and 3% had chronic kidney disease. In a multivariable model, which included comorbidities and traditional intraoperative risk factors, CVP (p < 0.0001), heart rate (p < 0.0001), cardiac index (p < 0.0001), and MAP (p < 0.0001), were strong predictors of AKI, and superseded factors such as surgery type and cardiopulmonary bypass duration. The cardiac index had a significant interaction with heart rate (p = 0.026); a faster heart rate had a differentiating effect on the relationship of cardiac index with AKI, where a higher heart rate heightened the risk of AKI primarily in patients with low cardiac output. There was also significant interaction observed between CVP and MAP (p = 0.009); where the combination of elevated CVP and low MAP had a synergistic effect on AKI incidence. CONCLUSIONS: Hemodynamic factors measured within a few hours of surgery showed a strong association with AKI. Furthermore, determinants of kidney perfusion, namely CVP and arterial pressure are interdependent; as are constituents of stroke volume, that is, cardiac output and heart rate.

[Multicenter retrospect analysis of early clinical features and analysis of risk factors on prognosis of elderly patients with severe burns].

Objective: To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis. Methods: This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results: Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions: The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

[Preliminary clinical application of novel magnetic navigation and ultrasound-guided percutaneous transhepatic cholangiography drainage through the right liver duct for malignant obstructive jaundice].

Objective: To analyze the clinical application value of a novel magnetic navigation ultrasound (MNU) combined with digital subtraction angiography (DSA) dual-guided percutaneous transhepatic biliary drainage (PTCD) through the right hepatic duct for the treatment of malignant obstructive jaundice. Methods: Randomized controlled trial. The clinical data of 64 patients with malignant obstructive jaundice requiring PTCD through the right hepatic duct at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province People's Hospital) from December 2018 to December 2021 were retrospectively analyzed. The MNU group (n=32) underwent puncture guided by a novel domestic MNU combined with DSA, and the control group (n=32) underwent puncture guided by traditional DSA. The operation time, number of punctures, X-ray dose after biliary stenting as shown by DSA, patients' tolerance of the operation, success rate of the operation, pre- and post-operative total bilirubin, and incidence of postoperative complications were compared between the two groups. Results: The operation time of the MNU group was significantly shorter than that of the control group [(17.8±7.3) vs. (31.6±9.9) min, t=-6.35,P=0.001]; the number of punctures in the MNU group was significantly lower [(1.7±0.6) vs. (6.3±3.9) times, t=-6.59, P=0.001]; and the X-ray dose after biliary stenting as shown by DSA in the MNU group was lower than that in the control group [(132±88) vs. (746±187) mGy, t=-16.81,P<0.001]; Five patients in the control group were unable to tolerate the operation, and two stopped the operation, however all patients in the MNU group could tolerate the operation, and all completed the operation, with a success rate of 100% (32/32) in the MNU group compared to 93.8%(30/32) in the control group; the common complications of PTCD were biliary bleeding and infection, and the incidence of biliary bleeding (25.0%, 8/32) and infection (18.8%, 6/32) in the MNU group was significantly lower than that in the control group, 53.1% (17/32) and 28.1% (9/32), respectively. Conclusion: Magnetic navigation ultrasound combined with DSA dual-guided PTCD through the right biliary system for the treatment of malignant obstructive jaundice is safe and feasible.

Low Muscle Mass by Preprocedural Computed Tomography Is Associated With Worse Short-Term Outcomes in Transcatheter Aortic Valve Replacement Recipients.

Low muscle mass (LMM) is associated with worse outcomes in various clinical situations. Traditional frailty markers have been used for preoperative risk stratification in patients who underwent transcatheter aortic valve replacement (TAVR). However, preoperative imaging provides an opportunity to directly quantify skeletal muscle mass to identify patients at higher risk of procedural complications. We reviewed all TAVR recipients from January to December 2018 and included subjects with preprocedural chest computed tomography. Multi-slice automated measurements of skeletal muscle mass were made from the ninth to twelfth thoracic vertebrae and normalized by height squared to obtain skeletal muscle index (cm2/m2). LMM was defined as the lowest gender-stratified skeletal muscle index tertile. Strength testing was collected during pre-TAVR evaluation. Primary outcome was a composite of perioperative complications, 1-year rehospitalization, or 1-year mortality. In our cohort, 238 patients met inclusion criteria, and 80 (33.6%) were identified to have LMM. Patients with LMM were older with lower body mass index, decreased grip strength, lower hemoglobin A1c, and higher N-terminal pro-brain natriuretic peptide. They had greater rates of the composite outcome and 2-year all-cause mortality, which remained significant on multivariable adjustment (hazard ratio 1.71, 95% confidence interval 1.05 to 2.78, p = 0.030 and hazard ratio 2.31, 95% confidence interval 1.02 to 5.24, p = 0.045, respectively) compared with patients without LMM; there was no significant difference in 5-year all-cause mortality. In conclusion, LMM was associated with an increase in the primary composite outcome and 2-year all-cause mortality in TAVR recipients. Using automatic muscle processing software on pre-TAVR computed tomography scans may serve as an additional preoperative risk stratification tool.