Transcatheter or Surgical Replacement for Failed Bioprosthetic Aortic Valves.

Importance: The use of valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) has been rapidly expanding as an alternative treatment to redo surgical aortic valve replacement (SAVR) for failed bioprosthetic valves despite limited long-term data. Objective: To assess mortality and morbidity in patients undergoing intervention for failed bioprosthetic SAVR. Design, Setting, and Participants: This was a retrospective population-based cohort analysis conducted between January 1, 2015, and December 31, 2020, with a median (IQR) follow-up time of 2.3 (1.1-4.0) years. A total of 1771 patients with a history of bioprosthetic SAVR who underwent ViV-TAVR or redo SAVR in California, New York, and New Jersey were included. Data were obtained from the California Department of Health Care Access and Information, the New York Statewide Planning and Research Cooperative System, and the New Jersey Discharge Data Collection System. Exclusion criteria included undergoing TAVR or redo SAVR within 5 years from initial SAVR, as well as infective endocarditis, concomitant surgical procedures, and out-of-state residency. Propensity matching yielded 375 patient pairs. Data were analyzed from January to December 2023. Interventions: ViV-TAVR vs redo SAVR. Main Outcomes and Measurements: The primary outcome was all-cause mortality. Secondary outcomes were stroke, heart failure hospitalization, reoperation, major bleeding, acute kidney failure, new pacemaker insertion, and infective endocarditis. Results: From 2015 through 2020, the proportion of patients undergoing ViV-TAVR vs redo SAVR increased from 159 of 451 (35.3%) to 498 or 797 (62.5%). Of 1771 participants, 653 (36.9%) were female, and the mean (SD) age was 74.4 (11.3) years. Periprocedural mortality and stroke rates were similar between propensity-matched groups. The ViV-TAVR group had lower periprocedural rates of major bleeding (2.4% vs 5.1%; P = .05), acute kidney failure (1.3% vs 7.2%; P < .001), and new pacemaker implantations (3.5% vs 10.9%; P < .001). The 5-year all-cause mortality rate was 23.4% (95% CI, 15.7-34.1) in the ViV-TAVR group and 13.3% (95% CI, 9.2-18.9) in the redo SAVR group. In a landmark analysis, no difference in mortality was observed up to 2 years (hazard ratio, 1.03; 95% CI, 0.59-1.78), but after 2 years, ViV-TAVR was associated with higher mortality (hazard ratio, 2.97; 95% CI, 1.18-7.47) as well as with a higher incidence of heart failure hospitalization (hazard ratio, 3.81; 95% CI, 1.57-9.22). There were no differences in 5-year incidence of stroke, reoperation, major bleeding, or infective endocarditis. Conclusions and Relevance: Compared with redo SAVR, ViV-TAVR was associated with a lower incidence of periprocedural complications and a similar incidence of all-cause mortality through 2 years' follow-up. However, ViV-TAVR was associated with higher rates of late mortality and heart failure hospitalization. These findings may be influenced by residual confounding and require adjudication in a randomized clinical trial.

Efficacy and Safety of Botulinum Toxin Type A for the Prevention of Postoperative Atrial Fibrillation.

BACKGROUND: Postoperative atrial fibrillation (POAF) is associated with increased morbidity and mortality. Epicardial injection of botulinum toxin may suppress POAF. OBJECTIVES: This study sought to assess the safety and efficacy of AGN-151607 for the prevention of POAF after cardiac surgery. METHODS: This phase 2, randomized, placebo-controlled trial assessed the safety and efficacy of AGN-151607, 125 U and 250 U vs placebo (1:1:1), for the prevention of POAF after cardiac surgery. Randomization was stratified by age (<65, ≥65 years) and type of surgery (nonvalvular/valve surgery). The primary endpoint was the occurrence of continuous AF ≥30 seconds. RESULTS: Among 312 modified intention-to-treat participants (placebo, n = 102; 125 U, n = 104; and 250 U, n = 106), the mean age was 66.9 ± 6.8 years; 17% were female; and 64% had coronary artery bypass graft (CABG) only, 12% had CABG + valve, and 24% had valve surgery. The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125-U group (relative risk [RR] vs placebo: 0.80; 95% CI: 0.58-1.10; P = 0.16), and 47.2% of the 250-U group (RR vs placebo: 1.04; 95% CI: 0.79-1.37; P = 0.78). The primary endpoint was reduced in the 125-U group in those ≥65 years (RR: 0.64; 95% CI: 0.43-0.94; P = 0.02) with a greater reduction in CABG-only participants ≥65 years (RR: 0.49; 95% CI: 0.27-0.87; P = 0.01). Rehospitalization and rates of adverse events were similar across the 3 groups. CONCLUSIONS: There were no significant differences in the rate of POAF with either dose compared with placebo; however, there was a lower rate of POAF in participants ≥65 years undergoing CABG only and receiving 125 U of AGN-151607. These hypothesis-generating findings require investigation in a larger, adequately powered randomized clinical trial. (Botulinum Toxin Type A [AGN-151607] for the Prevention of Post-operative Atrial Fibrillation in Adult Participants Undergoing Open-chest Cardiac Surgery [NOVA]; NCT03779841); A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Evaluate the Efficacy and Safety of Botulinum Toxin Type A [AGN 151607] Injections into the Epicardial Fat Pads to Prevent Post-Operative Atrial Fibrillation in Patients Undergoing Open-Chest Cardiac Surgery; 2017-004399-68).

Sex Bias in Prediction and Diagnosis of Cardiac Surgery Associated Acute Kidney Injury.

Background: Female sex has been recognized as a risk factor for cardiac surgery associated acute kidney injury (CS-AKI). The current study sought to evaluate whether female sex is a risk factor for CS-AKI, or modifies the association of peri-operative change in serum creatinine with CS-AKI. Methods: Observational study of adult patients undergoing cardiac surgery between 2000 and 2019 in a single U.S. center. The main variable of interest was registered patient sex, identified from electronic medical records. The main outcome was CS-AKI within 2 weeks of surgery. Results: Of 58526 patients, 19353 (33%) were female; 12934 (22%) incurred AKI based on ≥ 0.3 mg/dL or ≥ 50% rise in serum creatinine (any AKI), 3320 (5.7%) had moderate to severe AKI, and 1018 (1.7%) required dialysis within 2 weeks of surgery. Female sex was associated with higher risk for AKI in models that were based on preoperative serum creatinine (OR, 1.35; 95% CI, 1.29-1.42), and lower risk with the use of estimated glomerular filtration, (OR, 0.90; 95% CI, 0.86-0.95). The risk for moderate to severe CS-AKI for a given immediate peri-operative change in serum creatinine was higher in female compared to male patients (p < .0001 and p < .0001 for non-linearity), and the association was modified by pre-operative kidney function (p < .0001 for interaction). Conclusions: The association of patient sex with CS-AKI and its direction was dependent on the operational definition of pre-operative kidney function, and differential outcome misclassification due to AKI defined by absolute change in serum creatinine.

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.

Incidence, Risk Factors, and Outcomes Associated With Permanent Pacemaker Implantation Following Tricuspid Valve Surgery.

BACKGROUND: Data regarding permanent pacemaker (PPM) implantation following tricuspid valve surgery (TVS) are limited. We sought to evaluate its incidence, risk factors, and outcomes. METHODS AND RESULTS: Medicare beneficiaries who underwent TVS from 2013 to 2020 were identified. Patients who underwent TVS for endocarditis were excluded. The primary exposure of interest was new PPM after TVS. Outcomes included all-cause mortality and readmission with endocarditis or heart failure on follow-up. Among the 13 294 patients who underwent TVS, 2518 (18.9%) required PPM placement. Risk factors included female sex (relative risk [RR], 1.26 [95% CI, 1.17-1.36], P<0.0001), prior sternotomy (RR, 1.12 [95% CI, 1.02-1.23], P=0.02), preoperative second-degree heart block (RR, 2.20 [95% CI, 1.81-2.69], P<0.0001), right bundle-branch block (RR, 1.21 [95% CI, 1.03-1.41], P=0.019), bifascicular block (RR, 1.43 [95% CI, 1.06-1.93], P=0.02), and prior malignancy (RR, 1.23 [95% CI, 1.01-1.49], P=0.04). Tricuspid valve (TV) replacement was associated with a significantly higher risk of PPM implantation when compared with TV repair (RR, 3.20 [95% CI, 2.16-4.75], P<0.0001). After a median follow-up of 3.1 years, mortality was not different in patients who received PPM compared with patients who did not (hazard ratio [HR], 1.02 [95% CI, 0.93-1.12], P=0.7). PPM placement was not associated with a higher risk of endocarditis but was associated with a higher risk of heart failure readmission (HR, 1.28 [95% CI, 1.14-1.43], P<0.001). CONCLUSIONS: PPM implantation frequently occurs after TVS, notably in female patients and patients undergoing TV replacement. Although mortality is not increased, it is associated with higher rates of heart failure rehospitalization.

Sex-Specific Prognosis of Left Ventricular Size and Function Following Repair of Degenerative Mitral Regurgitation.

BACKGROUND: Prior studies have demonstrated worse long-term outcomes for women after surgery for severe mitral regurgitation (MR). The current Class I indications for surgery for severe degenerative MR use cutoffs of left ventricular end-systolic dimension (LVESD) and left ventricular ejection fraction (EF) that do not account for known sex-related differences. OBJECTIVES: The primary objective of this study was to assess long-term mortality following mitral valve repair in women compared with men on the basis of preoperative left ventricular systolic dimensions and EF. METHODS: Consecutive patients who underwent isolated mitral valve repair for degenerative MR at a single institution between 1994 and 2016 were screened. Adjusted HRs for all-cause mortality were compared according to baseline LVESD, LVESD indexed to body surface area (LVESDi), and EF for men and women. RESULTS: Among 4,589 patients, 1,825 were women (40%), and after a median follow-up period of 7.2 years, 344 patients (7.5%) had died. The risk for mortality for women increased from the baseline hazard at an LVESD of 3.6 cm, whereas an inflection point for increased risk with LVESD was not evident in men. Regarding LVESDi, the risk for women increased at 1.8 cm/m2 compared with 2.1 cm/m2 in men. For EF, women and men had a similar inflection point (58%); however, mortality was higher for women as EF decreased. CONCLUSIONS: After mitral valve repair, women have a higher risk for all-cause mortality at lower LVESD and LVESDi and higher EF. These results support consideration of sex-specific thresholds for LVESDi in surgical decision making for patients with severe MR.

The Society of Thoracic Surgeons 2023 Clinical Practice Guidelines for the Surgical Treatment of Atrial Fibrillation.

The Society of Thoracic Surgeons 2023 clinical practice guidelines for the surgical management of atrial fibrillation incorporate the most recent evidence for surgical ablation and left atrial appendage occlusion in different clinical scenarios. Substantial new evidence regarding the risks and benefits of surgical left atrial appendage occlusion and the long-term benefits of surgical ablation has been produced in the last five years. In comparison to the 2017 clinical practice guideline, the current update has an emphasis on surgical ablation in first-time, non-emergent cardiac surgery and its long-term benefits, an extension of the recommendation to perform surgical ablation in all patients with atrial fibrillation undergoing first-time, non-emergent cardiac surgery and a new class I recommendation for left atrial appendage occlusion in all patients with atrial fibrillation undergoing first-time, non-emergent cardiac surgery. Further guidance is provided for patients with structural heart disease and atrial fibrillation being considered for transcatheter valve repair or replacement, as well as patients in need of isolated left atrial appendage management who are not candidates for surgical ablation. The importance of a multidisciplinary team assessment, treatment planning, and long-term follow-up are reiterated in this clinical practice guideline with a class I recommendation, along with the other recommendations from the 2017 guidelines which remained unchanged in their class of recommendation and level of evidence.

Predictors and outcomes of discharge to long-term acute care facilities after cardiac surgery.

OBJECTIVE: An increasing number of patients with significant comorbidities present for complex cardiac surgery, with a subgroup requiring discharge to long-term acute care facilities. We aim to examine predictors and mortality after discharge to a long-term acute care facility. METHODS: From January 1, 2015, to April 30, 2021, all adult cardiac surgeries were queried and patients discharged to long-term acute care facilities were identified. Baseline characteristics, procedures, and in-hospital complications were compared between long-term acute care facility and non-long-term acute care facility discharges. Random forest analysis was conducted to establish predictors of discharge to long-term acute care facilities. Kaplan-Meier survival analysis was used to determine probability of survival over 7 years. Multivariate regression modeling was used to establish predictors of death after long-term acute care facility discharge. RESULTS: Of 29,884 patients undergoing cardiac surgery, 324 (1.1%) were discharged to a long-term acute care facility. The long-term acute care facility group had higher rates of urgent/emergency operation (54% vs 23%; 10% vs 3%, P < .001) and longer mean cardiopulmonary bypass (167 vs 110 minutes, P < .001). By random forest analysis, emergency/urgent status, longer cardiopulmonary bypass duration, redo surgery, endocarditis, and history of dialysis were the most predictive of discharge to a long-term acute care facility. Although the non-long-term acute care facility group demonstrated greater than 95% survival at 6 months, Kaplan-Meier survival analysis showed 28% 6-month mortality in the long-term acute care facility cohort. Random forest analysis demonstrated that chronic lung disease and postoperative respiratory complications were significant predictors of death at 6 months after discharge to a long-term acute care facility. CONCLUSIONS: Patients with chronic lung and kidney disease undergoing prolonged procedures are at higher risk to be discharged to long-term acute care facilities after surgery with worse survival. Efforts to minimize postoperative respiratory complications may reduce mortality after discharge to long-term acute care facilities.

Echocardiography Versus Magnetic Resonance Imaging Quantification and Novel Algorithm for Isolated Severe Tricuspid Regurgitation.

Transthoracic echocardiography (TTE) is the first-line tool to evaluate isolated tricuspid regurgitation (TR) but it has limitations and its TR quantification compared with magnetic resonance imaging (MRI) has been studied infrequently. We compared isolated severe TR quantification by TTE against MRI and developed a novel TTE-based algorithm. Isolated TR patients graded severe by TTE and who underwent MRI January 2007 to June 2019 were studied. The TTE and MRI measurements were analyzed by correlation, area under receiver-operative characteristics curve (AUC), and classification and regression tree algorithm of TTE parameters to best identify MRI-derived severe TR (regurgitant volume ≥45 ml and/or fraction ≥50%). A total of 108 of 262 (41%) that were graded as severe TR by TTE also had severe TR by MRI. There were moderate correlations between TTE and MRI in the quantification of TR severity and right atrial size (Pearson r = 0.428 to 0.645) but none to modest correlations between them in right ventricle quantification. The key TTE parameters to identify MRI-derived severe TR in the decision tree regression algorithm were right atrial volume indexed ≥47 ml/m2 and effective regurgitant orifice area ≥0.45 cm2 and especially if there is right ventricle free wall strain ≥ -9.5%. This novel algorithm has an AUC of 0.76% and 79% agreement to detect severe TR by MRI, which higher than the American Society of Echocardiography criteria with AUC 0.68% and 66% agreement (p = 0.006 and p <0.001, respectively). In conclusion, TTE-derived TR and right atrial quantification had moderate correlation and discrimination of severe TR by MRI, from which a novel TTE algorithm was derived, which had incrementally a higher accuracy than contemporary guidelines' criteria alone.

What determines outcomes in multivalve reoperations? Effect of patient and surgical complexity.

OBJECTIVE: Patient characteristics, risks, and outcomes associated with reoperative multivalve cardiac surgery are poorly characterized. Effect of patient variables and surgical components of each reoperation were evaluated with regard to operative mortality. METHODS: From January 2008 to January 2022, 2324 patients with previous cardiac surgery underwent 2352 reoperations involving repair or replacement of multiple cardiac valves at Cleveland Clinic. Mean age was 66 ± 14 years. Number of surgical components representing surgical complexity (valve procedures, aortic surgery, coronary artery bypass grafting, and atrial fibrillation procedures) ranged from 2 to 6. Random forest for imbalanced data was used to identify risk factors for operative mortality. RESULTS: Surgery was elective in 1327 (56%), urgent in 1006 (43%), and emergency in 19 (0.8%). First-time reoperations were performed in 1796 (76%) and 556 (24%) had 2 or more previous operations. Isolated multivalve operations comprised 54% (1265) of cases; 1087 incorporated additional surgical components. Two valves were operated on in 80% (1889) of cases, 3 in 20% (461), and 4 in 0.09% (2). Operative mortality was 4.2% (98 out of 2352), with 1.7% (12 out of 704) for elective, isolated multivalve reoperations. For each added surgical component, operative mortality incrementally increased, from 2.4% for 2 components (24 out of 1009) to 17% for ≥5 (5 out of 30). Predictors of operative mortality included coronary artery bypass grafting, surgical urgency, cardiac, renal dysfunction, peripheral artery disease, New York Heart Association functional class, and anemia. CONCLUSIONS: Elective, isolated reoperative multivalve surgery can be performed with low mortality. Surgical complexity coupled with key physiologic factors can be used to inform surgical risk and decision making.

Survival and repair durability in patients undergoing concomitant aortic valve reimplantation and mitral valve repair.

Objective: The study objective was to determine repair durability and survival in patients with and without connective tissue disorders undergoing concomitant aortic valve reimplantation and mitral valve repair. Methods: From 2002 to 2019, 68 patients underwent concomitant aortic valve reimplantation and mitral valve repair, including 27 patients with Marfan syndrome (39.7%). Follow-up echocardiograms were analyzed using nonlinear multiphase mixed-effects cumulative logistic regression. The regurgitation grade over time was estimated by averaging patient-specific profiles. Survival and freedom from reoperation were estimated by the Kaplan-Meier method. Results: At 7 years, 11% of patients had aortic insufficiency greater than mild (severe in 2 patients). There was no difference in greater than mild aortic insufficiency between patients with or without Marfan syndrome (P = .37). Twenty percent of patients had progressed to mitral regurgitation greater than mild (severe in only 1 patient). The prevalence of recurrent mitral regurgitation was higher in those without Marfan syndrome, with greater than mild regurgitation increasing to 24% by 2 years and remaining constant thereafter (P = .04). Freedom from reoperation on the aortic valve or mitral valve was 83% at 10 years and did not differ between Marfan syndrome groups. There were no cases of perioperative mortality. Survival at 5 and 10 years was 94% and 87%, respectively, without a difference between those with and without Marfan syndrome. Conclusions: Patients can undergo a total repair strategy using combined aortic valve reimplantation and mitral valve repair procedures with a low risk of mortality and complications, with favorable freedom from both residual valve regurgitation and reoperation.

Temporal Trends in the United States Patent Landscape: Innovation in Cardiology Across Industry and Academia.

Background: Novel approaches to diagnostics and therapeutics in medical care reflect the scientific community's evolving understanding of disease states and their clinical implications. Marketable and valuable innovations are generally patented for protection of intellectual property. Here, we explore the landscape of cardiology-related patents in the United States. Methods: All United States patents granted between 2005 and 2020 were included in this study. Keywords filtering was used to identify patents related to cardiovascular medicine. Statistical inference was conducted with the Mann-Kendall trend and analysis of variance tests. The results in this report are entirely reproducible with Python and R scripts available in a publicly accessible repository. Results: Of the 4,453,733 patents issued by the USPTO between 2005 and 2020, 31,048 (0.7%) were identified as cardiology-related patents. We identified the top 10 institutions within the for-profit and not-for-profit categories that were assigned the most cardiology-related patents in this time period. Distributions of number of patents per inventor were heavily right-skewed, with a small number of inventors responsible for a large number of patents each. Patents in the cardiac imaging subgroup took the longest to gain approval after submission (median delay: 3.6 years). Conclusions: By studying the patent universe, we are able to identify underexplored areas within cardiovascular medicine. Obstacles such as long delays between patent application and approval can hamper innovation within a field. As a next step, we aim to use these results to predict the next area within cardiovascular medicine to undergo explosive research and innovation.

Comparison of Outcomes and Discharge Location After Transcatheter vs. Surgical Aortic Valve Replacement With Prior Coronary Artery Bypass Grafting.

Background: Published trials have shown that transcatheter aortic valve replacement (TAVR) is a safe alternative to surgical aortic valve replacement (SAVR) after prior coronary artery bypass grafting (CABG). However, differences in morbidity and discharge location between the 2 procedures are less thoroughly characterized. Methods: From January 1, 2006 to January 7, 2020, 1059 patients with severe aortic stenosis after CABG underwent either SAVR (n = 315/30%), transfemoral TAVR (TF-TAVR) (n = 575/54%), or alternative access TAVR (n = 169/16%) at a single, tertiary care, academic institution. Propensity-weighted matching was used to compare morbidity, mortality, length of postprocedure stay, and nonhome discharge between TF-TAVR (effective n = 163) and SAVR (effective n = 163) groups. Results: Among propensity-weighted groups, the TF-TAVR group experienced fewer transfusions than the SAVR group (effective n = 16 [9.5%] vs. 132 [81%]; p < 0 .0001), less new-onset atrial fibrillation (effective n = 5.1 [3.1%] vs. 43 [27%]; p = 0.009), and less prolonged mechanical ventilation >24 â€‹hours (effective n = 0.41 [0.25%] vs. 30 [18%]; p <0.0001). Permanent pacemaker implant was 9.3% (effective n = 13) after TF-TAVR vs. 5.5% (effective n = 7.9; p = 0.2) after SAVR, stroke 0.41% (effective n = 0.67) vs. 2.1% (effective n = 3.5; p = 0.2), and operative mortality 0.5% (effective n = 0.8) vs. 1.7% (effective n = 2.8; p = 0.8). The TF-TAVR group had shorter postprocedure lengths of stay (2.0 vs. 7.6 days; p < 0.0001). Discharge home was more common after TF-TAVR than SAVR (effective n = 156 [95%] vs. 118 [73%]; p = 0.01). Conclusions: For patients developing severe aortic stenosis after CABG, TF-TAVR rather than SAVR should be strongly considered because of lower morbidity, shorter length of stay, and greater likelihood of home discharge.

Novel functional atrial fibrillation risk genes and pathways identified from coexpression analyses in human left atria.

BACKGROUND: Genomewide association studies have associated >100 genetic loci with atrial fibrillation (AF), but establishing causal genes contributing to AF remains challenging. OBJECTIVE: The purpose of this study was to determine candidate novel causal genes and mechanistic pathways associated with AF risk loci by incorporating gene expression and coexpression analyses and to provide a resource for functional studies and targeting of AF-associated genes. METHODS: Cis-expression quantitative trait loci were identified for candidate genes near AF risk variants in human left atrial tissues. Coexpression partners were identified for each candidate gene. Weighted gene coexpression network analysis (WGCNA) identified modules and modules with overrepresentation of candidate AF genes. Ingenuity pathway analysis (IPA) was applied to the coexpression partners of each candidate gene. IPA and gene set over representation analysis were applied to each WGCNA module. RESULTS: One hundred sixty-six AF-risk single nucleotide polymorphisms were located in 135 loci. Eighty-one novel genes not previously annotated as putative AF risk genes were identified. IPA identified mitochondrial dysfunction, oxidative stress, epithelial adherens junction signaling, and sirtuin signaling as the most frequent significant pathways. WGCNA characterized 64 modules (candidate AF genes overrepresented in 8), represented by cell injury, death, stress, developmental, metabolic/mitochondrial, transcription/translation, and immune activation/inflammation regulatory pathways. CONCLUSION: Candidate gene coexpression analyses suggest significant roles for cellular stress and remodeling in AF, supporting a dual risk model for AF: Genetic susceptibility to AF may not manifest until later in life, when cellular stressors overwhelm adaptive responses. These analyses also provide a novel resource to guide functional studies on potential causal AF genes.

Risk of Surgical Mitral Valve Repair for Primary Mitral Regurgitation.

BACKGROUND: Risk estimation for surgical intervention is an essential component of heart team shared decision-making. However, current mitral valve (MV) surgery risk models used in practice lack etiologic or procedural specificity. OBJECTIVES: The purpose of this study was to establish a comprehensive method for assessment of operative risk of MV repair of primary mitral regurgitation (MR). METHODS: A novel etiology and procedure-specific algorithm identified 53,462 consecutive (July 2014 to June 2020) intention-to-treat MV repair patients with primary MR from The Society of Thoracic Surgeons Adult Cardiac Surgery Database. Risk models were fit for 30-day operative mortality, mortality and/or major morbidity, and conversion-to-replacement (CONV). As-treated mortality and morbidity models were derived separately. RESULTS: Event rates for mortality (n = 619; 1.16%), mortality plus morbidity (n = 4,746; 8.88%), and CONV (n = 3,399; 6.36%) were low. Mortality was higher in CONV patients vs repair (3.18% vs 1.02%). All event rates were lower with increasing program volumes. The mortality risk model had excellent discrimination (AUC: 0.807) and calibration and confirmed very low mortality risk for isolated MV repair for primary MR, with mean mortality risk of 1.16% and median of 0.55% (IQR: 0.30%-1.17%) with 90th and 95th percentiles 2.48% and 3.99%, respectively. The mortality risk was <0.5% in patients <65 years of age, with 97% of the total population across age groups having a risk of <3%. Only 1 in 4 patients age 75 or older had >3% estimated risk of mortality. CONCLUSIONS: This etiologic and procedure-specific risk model establishes that the contemporary mortality risk of MV repair for primary MR is <1% for the vast majority of patients.

Risk of Surgical Mitral Valve Repair for Primary Mitral Regurgitation.

BACKGROUND: Risk estimation for surgical intervention is an essential component of heart team shared decision-making. However, current mitral valve (MV) surgery risk models used in practice lack etiologic or procedural specificity. The purpose of this study was to establish a comprehensive method for assessment of operative risk of MV repair of primary mitral regurgitation (MR). METHODS: A novel etiology and procedure-specific algorithm identified 53,462 consecutive (July 2014 to June 2020) intention-to-treat MV repair patients with primary MR from The Society of Thoracic Surgeons Adult Cardiac Surgery Database. Risk models were fit for 30-day operative mortality, mortality and/or major morbidity, and conversion-to-replacement (CONV). As-treated mortality and morbidity models were derived separately. RESULTS: Event rates for mortality (n = 619; 1.16%), mortality plus morbidity (n = 4746; 8.88%), and CONV (n = 3399; 6.36%) were low. Mortality was higher in CONV patients vs repair (3.18% vs 1.02%). All event rates were lower with increasing program volumes. The mortality risk model had excellent discrimination (AUC: 0.807) and calibration and confirmed very low mortality risk for isolated MV repair for primary MR, with mean mortality risk of 1.16% and median of 0.55% (interquartile range: 0.30%-1.17%) with 90th and 95th percentiles 2.48% and 3.99%, respectively. The mortality risk was <0.5% in patients <65 years of age, with 97% of the total population across age groups having a risk of <3%. Only 1 in 4 patients age 75 or older had >3% estimated risk of mortality. CONCLUSIONS: This etiologic and procedure-specific risk model establishes that the contemporary mortality risk of MV repair for primary MR is <1% for the vast majority of patients.