Non-invasive prenatal testing of beta-hemoglobinopathies using next generation sequencing, in-silico sequence size selection, and haplotyping.

AIM: To develop a non-invasive prenatal test for beta-hemoglobinopathies based on analyzing maternal plasma by using next generation sequencing. METHODS: We applied next generation sequencing (NGS) of maternal plasma to the non-invasive prenatal testing (NIPT) of autosomal recessive diseases, sickle cell disease and beta-thalassemia. Using the Illumina MiSeq, we sequenced plasma libraries obtained via a Twist Bioscience probe capture panel covering 4 Kb of chromosome 11, including the beta-globin (HBB) gene and >450 genomic single-nucleotide polymorphisms (SNPs) used to estimate the fetal fraction (FF). The FF is estimated by counting paternally transmitted allelic sequence reads present in the plasma but absent in the mother. We inferred fetal beta-globin genotypes by comparing the observed mutation (Mut) and reference (Ref) read ratios to those expected for the three possible fetal genotypes (Mut/Mut; Mut/Ref; Ref/Ref), based on the FF. RESULTS: We bioinformatically enriched the FF by excluding reads over a specified length via in-silico size selection (ISS), favoring the shorter fetal reads, which increased fetal genotype prediction accuracy. Finally, we determined the parental HBB haplotypes, which allowed us to use the read ratios observed at linked SNPs to help predict the fetal genotype at the mutation site(s). We determined HBB haplotypes via Oxford Nanopore MinION sequencing of a 2.2 kb amplicon and aligned these sequences using Soft Genetics' NextGENe LR software. CONCLUSION: The combined use of ISS and HBB haplotypes enabled us to correctly predict fetal genotypes in cases where the prediction based on variant read ratios alone was incorrect.

Transcatheter vs surgical aortic valve replacement in patients with interstitial lung disease.

BACKGROUND: Patients with underlying interstitial lung disease (ILD) who undergo cardiac surgery are at high risk of postoperative pulmonary complications. It remains unclear if transcatheter aortic valve replacement (TAVR) offers any benefit over surgical aortic valve replacement (SAVR) in ILD patients with severe aortic stenosis. METHODS: All adult patients with a diagnosis of ILD who underwent either a TAVR or isolated SAVR between January 2002 and December 2017 were retrospectively reviewed. Operative mortality, 30-day readmissions, and adjusted 1-year survival were compared between the two cohorts. RESULTS: The overall cohort included 52 TAVR and 74 SAVR patients. While TAVR patients were significantly older (77.2 vs 72.9 years) with higher Society of Thoracic Surgeons predicted risk of mortality (STS-PROM) scores compared with SAVR patients (6.29 vs 4.49; all P < .02), operative mortality was similar (5.8% vs 4.1%; P = .45). Rates of postoperative stroke, permanent pacemaker implantation, reintubation, and 30-day readmissions did not differ between the two groups (all P > .46). However, TAVR was associated with significantly shorter hospital and intensive care unit (ICU) length of stay, shorter ventilation times, and less requirement for ICU admission (all P < .05). Thirty-day readmissions and adjusted 1-year survival were also similar between the two groups (hazard ratio for TAVR vs SAVR = 1.34; 95% CI: 0.7-2.6). CONCLUSIONS: Among ILD patients with symptomatic aortic stenosis, TAVR was associated with comparable operative and risk-adjusted 1-year survival to SAVR. TAVR patients also had shorter ventilator times, ICU and hospital stay despite being at higher risk. Together, our findings suggest that TAVR may be a better option in this unique cohort.

Chronic opioid use after coronary bypass surgery.

BACKGROUND: Opioid dependence has become a major health care issue. Pain management of invasive surgical procedures with opioids may potentially contribute to this epidemic. We sought to determine the association of opioid-prescribing patterns with chronic opioid use. METHODS: We retrospectively reviewed all patients undergoing isolated coronary artery bypass graft (CABG) procedures during 2016 at a single institution. Prescribing patterns and medication usage were compared between opioid-naïve and opioid-exposed patients (patients with reported opioid use within 30 days prior to surgery). Chronic opioid dependence was defined as opioid usage beyond 90 days after discharge. RESULTS: We included 284 opioid-naïve and 46 opioid-exposed patients. Although overall prescribing patterns were similar between groups, a higher proportion of opioid-exposed patients were prescribed a total dose >150 mg of oxycodone per discharge prescription (15.2% vs 4.9%; P = 0.024), and had a higher proportion of refills within 30 days (28.3% vs 10.9%; relative risk [RR] 3.2 [95% confidence interval (CI): 1.5-6.8]; all P < 0.05). The incidence of chronic opioid dependence was higher among opioid-exposed patients compared to opioid-naïve patients (21.7% vs 3.2%; RR 8.5 [95%CI: 3.2-22.3]; P = 0.001). CONCLUSIONS: Ongoing opioid use 3 months after CABG is present in 21.7% of opioid-exposed patients and 3.2% of opioid-naïve patients. These preliminary findings highlight the burden of prescribing patterns on the overall opioid epidemic and the need to develop alternative pain management strategies.

Clinical Significance of Greater Implantation Height with SAPIEN 3 Transcatheter Heart Valve.

BACKGROUND: A lower rate of permanent pacemaker (PPM) has been linked to a target aortic implantation height (AIH) >0.70, following transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve. Based on clinical experience, it was hypothesized that a higher AIH (≥0.85) would lower the rate of PPM implantation. METHODS: A total of 127 patients (66 females, 61 males; mean age 82 ± 8 years) underwent TAVR with the SAPIEN 3 valve between May 2015 and July 2016. AIH was defined as the proportion of the valve frame above the aortic annulus in the post-deployment aortogram. A target AIH (≥0.70) was achieved in 113 patients (89%). Cases were stratified into a High Implantation (HI) group (AIH ≥0.85; 33 patients) or a Standard Implantation (SI) group (AIH <0.85; 94 patients). RESULTS: The mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score of all patients was 6.4 ± 3.5%. Preoperative right bundle branch block (RBBB) was prevalent in 13% of SI patients, and in 18% of HI patients (p = 0.56). There were no significant differences in operative mortality (3.2% versus 0%), median length of stay (2 days versus 3 days) and incidence of moderate-to-severe paravalvular leak (3.2% versus 0%; all p >0.410) between SI and HI patients, respectively. Likewise, the incidence of new PPM did not differ between the two groups (12% in HI versus 13% in SI; p ≥0.99). The mean AIH was similar for patients with PPM implantation (0.80 ± 0.08) compared to those without (0.78 ± 0.06; p = 0.520). Preoperative RBBB was significantly associated with PPM implantation (odds ratio (OR) 10.1; p = 0.002), and patients who underwent PPM implantation had a higher operative mortality (12.5% versus 1%; p = 0.040). CONCLUSIONS: Among TAVR patients who received the SAPIEN 3 heart valve, a higher AIH (≥0.85) was not associated with a lower rate of PPM implantation or increased operative mortality. Prior RBBB was the only independent risk factor for new PPM implantation. Long-term follow up is crucial in determining the clinical significance of PPM implantation.

Surgical pulmonary embolectomy and catheter-directed thrombolysis for treatment of submassive pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE) with preserved hemodynamics but right ventricular dysfunction, classified as submassive PE, carries a high risk of mortality. We report the results for patients who did not qualify for medical therapy and required treatment of submassive PE with surgical pulmonary embolectomy and catheter-directed thrombolysis (CDT). METHODS: Between October 1999 and May 2015, 133 submassive PE patients underwent treatment with pulmonary embolectomy (71) and CDT (62). A multidisciplinary PE response team helped to determine the most appropriate treatment strategy on a case-by-case basis. The EkoSonic ultrasound-facilitated thrombolysis system (EKOS) was used for CDT, which was introduced in 2010. RESULTS: The mean age of submassive PE patients was 57.3 years, which included 36.8% females. PE risk factors included previous deep venous thrombosis (46.6%), immobility (36.1%), recent surgery (30.8%), and cancer (22.6%), P < 0.05. The most common indication for advanced treatment was right ventricular strain (42.9%), P = 0.03. The frequency of surgical pulmonary embolectomy remained stable even after incorporating the EKOS procedure into our treatment algorithm, with statistically similar operative mortality. Bleeding was observed in six CDT patients and one pulmonary embolectomy patient (P < 0.05). Follow-up echocardiography was available for 61% of the overall cohort, of whom 76.5% had no residual moderate or severe right ventricular dysfunction. CONCLUSIONS: Pulmonary embolectomy and CDT are important contemporary advanced treatment options for selected high-risk patients with submassive PE, who do not qualify for medical therapy.

Impact of Prosthesis Size and Prosthesis-Patient Mismatch on Outcomes in Younger Female Patients Undergoing Aortic Valve Replacement.

The effects of patient-prosthesis mismatch (PPM) after surgical aortic valve replacement (SAVR) suggest worse outcomes with smaller valves. We assessed clinical outcomes of younger females undergoing SAVR, using small and large prostheses, and the incremental risk of PPM. Between January 2002 and June 2015, 451 younger (age ≤65 years) female patients underwent SAVR. Patients were stratified into small prostheses (SP) ≤21 mm (n = 256) and large prostheses (LP) ≥23 mm (n = 195) groups. PPM was classified as moderate if indexed effective orifice area (iEOA) 0.65-0.85 cm2/m2, or severe if iEOA <0.65 cm2/m2. Operative mortality was not statistically different between SP and LP groups (2.4% vs 0.5%; P = 0.146). Unadjusted 10-year survival was 82% (95% confidence interval 77-87%), and was similar in both groups (P = 0.210). When grouped by standard PPM thresholds, only severe PPM was associated with significantly decreased survival (P = 0.007). A significant survival decrease was detected in LP group with iEOA ≤0.75 cm2/m2 (P < 0.001). Among SP patients, iEOA ≤0.65 cm2/m2 was associated with increased mortality (P = 0.075). After adjusting for potential confounders, Cox proportional hazard model identified iEOAs of ≤0.65 cm2/m2 (hazard ratio 1.85; P = 0.066) and ≤0.75 cm2/m2 (hazard ratio 2.3; P ≤ 0.003) as predictors of decreased long-term survival, in SP and LP groups, respectively. Among younger females who underwent SAVR, postoperative complications and in-hospital outcomes were substantially similar between the SP and LP groups. However, patients who received LP were adversely affected at lesser degrees of PPM than those who received SP. While SP patients may tolerate until iEOA ≤0.65 cm2/m2, our results suggest that moderate PPM of iEOA ≤0.75 for LP patients should be avoided.

Sex-based differences in mitral valve Re-operation after mitral valve repair: Truth or myth?

BACKGROUND: Outcomes after mitral valve (MV) repair are known to be worse in women. Less is known about sex-based differences in MV repair durability. METHODS: All adult patients undergoing MV repair from 2002 to 2016 were reviewed. Of 2463 cases, 947 (39%) were women. Re-operation risk was defined as any intervention for repair failure or MV disease progression. Median follow-up was 8.2 years. RESULTS: Women were older with higher STS-risk scores and were more likely to have rheumatic disease (RHD). Operative mortality was clinically higher in women (2.7% vs 1.7%; P = 0.09). Although women had significantly higher 10-year re-operation risk (7% vs 4%), adjusted longitudinal analysis showed that this was associated with RHD in women (HR 4.04; P = 0.001). Female sex alone was not a significant predictor (P = 0.21). CONCLUSIONS: Re-operation following MV repair was infrequent. Women had increased re-operation risk that was largely attributable to their worse preoperative profiles rather than female sex alone.

Proximal aortic surgery in the elderly population: Is advanced age a contraindication for surgery?

OBJECTIVE: The study objective was to describe the clinical outcomes of elderly patients undergoing ascending aortic surgery. METHODS: Patients aged 70 years or older who underwent ascending aortic surgery between January 2002 and December 2013 were examined. Of 415 included patients, 285 were elderly patients (age 70-79 years) and 130 were very elderly (age ≥80 years). Logistic regression and Cox proportional hazards models were used to evaluate operative mortality and long-term survival, respectively. RESULTS: Surgical indications included aortic aneurysm (63.1%), calcified aorta with need for other cardiac procedure (26.4%), and type A dissection (10.5%). Compared with elderly patients, the very elderly patients had a higher burden of comorbidities and operative mortality (13% vs 7%, P < .04). The very elderly patients were also more likely to be discharged to a rehabilitation facility than home (P < .001). However, risk-adjusted operative mortality and 30-day readmissions rates were similar (P > .05). Kaplan-Meier estimates of survival at 1 and 5 years were 85.6% and 72.6% for elderly patients versus 79.2% and 57.1% for the very elderly patients. Age was a strong risk variable for late mortality in the unadjusted and adjusted analyses. CONCLUSIONS: After adjusting for these comorbidities, the cause of aortic disease, and the type of procedure, age was not an independent predictor of operative mortality, but was strongly associated with reduced late survival. Thus, advanced age alone should not be an absolute contraindication for ascending aortic surgery.

Mitral valve repair using edge-to-edge technique in various situations: real-world experiences.

OBJECTIVES: Edge-to-edge (E2E) mitral valve repair (MVP) is a versatile technique used in various situations for mitral regurgitation (MR). This technique has been regaining attention, given the increasing use of the MitraClip procedure. This real-world study evaluates the durability of the E2E technique in different settings. METHODS: From January 2002 to May 2015, a total of 303 patients with at least moderate MR who underwent E2E MVP were identified. Patients undergoing isolated MVP (n = 133) and concomitant coronary artery bypass grafting or other valvular procedures (N = 170) were included. Cox proportional hazards modelling was used to evaluate the risk factors for cumulative survival, or MV event (i.e. MV reintervention or MR recurrence) while event-free survival-defined as time to composite outcome of either death or MV event-was determined using competing risk Kaplan-Meier analysis. Median follow-up duration was 6.9 (interquartile range 5.8) years. RESULTS: The most common MR aetiology was myxomatous (34%), followed by Barlow's disease (27.7%), and ischaemic (21.5%). E2E MVP was performed for the following indications: persistent MR (51.5%), systolic anterior motion prophylaxis (22.1%), transaortic approach (17.5%) and systolic anterior motion treatment post-MVP (8.9%). Concomitant ring annuloplasty was performed in 224 patients (73.9%). Operative mortality was 3.6% and MV event rate was 18.5%. Significant predictors of decreased survival included age, renal insufficiency, peripheral vascular disease and ischaemic MR aetiology (all P < 0.050). No ring annuloplasty (HR 2.79; P < 0.001) was the only significant predictor of MV events. Estimated event-free survival for the overall cohort was 8.5 years, and shortest for functional (non-ischaemic; 6.6 years) and ischaemic aetiology (5.5 years). CONCLUSIONS: E2E repair is a versatile MVP technique, which can be used in prevention and treatment of systolic anterior motion, transaortic approach or with concomitant techniques, with reasonable outcomes. Ischaemic aetiology and absence of ring annuloplasty were associated with worse cumulative survival and MV event rates, respectively, which raises some concern in light of the expanding indication for MitraClip system.

Significance of Interstitial Lung Disease on Outcomes Following Cardiac Surgery.

Interstitial lung disease (ILD) is a known risk factor for noncardiac surgery due to acute pulmonary exacerbations but its impact after cardiac surgery is not known. We examined perioperative outcomes and risk factors for long-term survival in ILD patients who underwent cardiac surgery. From January 2002 to June 2017, 294 cardiac surgery patients with a previous ILD diagnosis, including 75 patients with idiopathic pulmonary fibrosis (IPF), were identified. A comparison cohort of 1,481 non-ILD patients was selected based on a priori variables. Long-term survival was evaluated using Cox proportional hazard modeling. Median follow-up was 6.4 years. ILD patients had higher postoperative mortality, reintubation rates, longer intensive care unit stay, and higher 30-day readmission rates (all p <0.05). Kaplan-Meier estimates of survival at 1, 5, and 10 years were 89%, 62%, and 37% for the non-IPF ILD cohort, 89%, 50%, and 13% for the IPF cohort, and 95%, 82%, and 67% for the comparison cohort, respectively (overall p <0.001). These significant differences in survival persisted in our risk-adjusted survival analysis. Adjusted survival analysis identified IPF (hazard ratio 3.04) and ILD (non-IPF; hazard ratio 1.78) as significant contributors to all-cause mortality. However, there were no changes in pulmonary function tests after 48 months postprocedure. In conclusion, ILD patients who underwent cardiac surgery have increased operative mortality, reintubation rates, longer intensive care unit, and higher 30-day readmissions compared with non-ILD patients. Moreover, severity of ILD, especially in IPF, appears to be associated with shorter long-term survival. In these patients, pulmonary risk stratification and multidisciplinary team approach are crucial.

Current Readings: An Update on Prevention and Management of Atrial Fibrillation Post Cardiac Surgery.

Atrial fibrillation (afib) remains the most common complication following cardiac surgery and is associated with increased mortality and resource utilization. As increasing number of patients with multiple comorbidities undergo cardiac surgery, and, given the overall burden of afib in the perioperative setting, there is growing interest among clinicians to improve diagnosis and management of afib among cardiac surgery patients. Advances in technology, refinements in surgical techniques, and innovations in drug development also contributed to this changing landscape. Despite the promising results of recently published studies on afib management following cardiac surgery, afib remains a complex problem with various presentations. Although myriad medical and surgical therapies for high-risk patients exist, determining patient-specific optimal treatment can be difficult. Understanding the context and relevance of contemporary studies is therefore critical to ensure appropriate patient selection and reduction of overall morbidity and mortality. This review closely examines 5 timely articles that delineate the most important results in the management of afib after cardiac surgery in the current era.

Minimally invasive versus full sternotomy aortic valve replacement in low-risk patients: Which will stand against transcatheter aortic valve replacement?

BACKGROUND: Minimally invasive aortic valve replacement using upper-hemisternotomy has been associated with improved results compared to full sternotomy aortic valve replacement. Given the likely expansion of transcatheter aortic valve replacement to low-risk patients, we examine contemporary outcomes after full sternotomy and minimally invasive aortic valve replacement in low-risk patients using our 15-year experience. METHODS: Two thousand ninety-five low-risk patients (Society of Thoracic Surgeons Predicted Risk of Mortality score <4) underwent elective isolated aortic valve replacement, including 1,029 (49%) minimally invasive and 1,066 (51%) full sternotomy, from 2002 to 2015. RESULTS: Compared to minimally invasive aortic valve replacement patients, full sternotomy aortic valve replacement patients had a greater burden of comorbidities, including diabetes, stroke, congestive heart failure, and predicted risk of mortality (all P ≤ .05). Operative mortality, stroke, and reoperation rates for bleeding were similar. There was a clinical trend toward shorter median intensive care unit stay and significantly shorter hospital length of stay among minimally invasive aortic valve replacement patients. Adjusted survival analysis identified age, chronic kidney disease, prior sternotomy, and congestive heart failure as predictors of decreased survival (all P ≤ .05), while type of intervention approach was nonsignificantly different. CONCLUSION: In low-risk patients, minimally invasive aortic valve replacement results in similar mortality, stroke, reoperation rates for bleeding, and midterm survival (after adjusting for confounders), but shorter hospital length of stay and a trend (P = .075) toward shorter intensive care unit stay, compared to full sternotomy aortic valve replacement. Therefore, minimally invasive aortic valve replacement should stand as a benchmark against transcatheter aortic valve replacement in these patients.

Mechanical Versus Bioprosthetic Aortic Valve Replacement in Patients Aged 50 Years and Younger.

BACKGROUND: This study evaluated outcomes in younger patients, specifically aged 50 years and younger, after mechanical aortic valve replacement (mAVR) and bioprosthetic AVR (bAVR). METHODS: From 1994 to 2016, 643 patients underwent AVR (411 mAVR and 232 bAVR) at age 50 or younger. Concomitant coronary artery bypass grafting and mitral valve procedures were also included. Propensity score-matching methods resulted in 170 evenly matched patient pairs. Primary end points were operative mortality and long-term survival. Secondary end points were stroke, major bleeding, and redo AVR. Median observation time was 8.1 years (range, 0 to 23.6 years). RESULTS: Overall, mean age was 41.9 years, and 29.3% were women, with an increasing trend toward use of bAVR. Mean age in the matched patients was 43.3 years for both cohorts (p = 0.68). Operative mortality, stroke, atrial fibrillation, reoperation for bleeding, and readmission rates within 30 days were all similar between the two groups. bAVR patients were at higher risk for redo AVR (13% vs 1.6%, p < 0.001), and mAVR patients were at higher risk for major bleeding events (8.5% vs 2.2%, p = 0.006). However, when adjusted, there were no differences in midterm and long-term survival between unmatched and matched cohorts. CONCLUSIONS: The increased risk of reoperation for bAVR and major bleeding incidents for mAVR was not reflected in midterm and long-term survival differences between the two groups. Our results suggest that bAVR may be an acceptable prosthesis choice for some patients aged 50 years and younger, although the results should be taken with caution.

Novel fast-track recovery protocol for alternative access transcatheter aortic valve replacement: application to non-femoral approaches.

OBJECTIVES: Although the transfemoral approach for transcatheter aortic valve replacement is the preferred choice, alternative access remains indicated for inadequate iliofemoral vessels. We report the successful implementation of a novel fast-track (FT) protocol for patients undergoing alternative access transcatheter aortic valve replacement compared with conventional controls. METHODS: Between September 2014 and January 2017, 31 and 23 patients underwent alternative access transcatheter aortic valve replacement under FT and pre-fast-track (p-FT) protocols, respectively. Comparisons of outcomes (in terms of mortality, complications, readmissions and resource utilization) were made before and after the implantation of the FT protocol in September 2015. RESULTS: Overall, mean age was 78.7 years in FT and 79.6 years in p-FT patients (P = 0.71). There were no significant differences in procedural (3.2% vs 13.0%, P = 0.301) or 90-day mortality (3.2% vs 17.4%, P = 0.151) between the FT and p-FT groups, respectively. Compared with p-FT patients, FT patients had significantly shorter intensive care unit stays (12 h vs 27 h, P = 0.006) and a trend towards more discharges within 3 days (41.9% vs 17.4%, P = 0.081). Resource utilization analyses projected a 56% and 17% reduction in the mean intensive care unit time (hours) per 100 patients and the total length of stay (days) per 100 patients, respectively, with respect to the FT approach. CONCLUSIONS: This pilot study demonstrates the feasibility and safety of the novel FT protocol for alternative access transcatheter aortic valve replacement, resulting in shorter intensive care unit stays, without increasing procedural complications or readmissions. With the expected increase in transcatheter aortic valve replacement utilization, FT protocols should be integrated with a multidisciplinary heart team approach to enhance patient recovery and optimize resource utilization.

Modeling lifetime costs and health outcomes attributable to secondhand smoke exposure at home among Korean adult women.

PURPOSE: The aim of this research is to estimate lifetime costs and health consequences for Korean adult women who were exposed to secondhand smoke (SHS) at home. METHODS: A Markov model was developed to project the lifetime healthcare costs and health outcomes of a hypothetical cohort of Korean women who are 40 years old and were married to current smokers. The Korean epidemiological data were used to reflect the natural history of SHS-exposed and non-exposed women. The direct healthcare costs (in 2014 US dollars) and quality-adjusted life years (QALYs) were annually discounted at 5% to reflect time preference. The time horizon of the analysis was lifetime and the cycle length was 1 year. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: In the absence of SHS exposure, Korean women will live 41.32 years or 34.56 QALYs before discount, which corresponded to 17.29 years or 15.35 QALYs after discount. The SHS-exposed women were predicted to live 37.91 years and 31.08 QALYs before discount and 16.76 years and 14.62 QALYs after discount. The estimated lifetime healthcare cost per woman in the SHS non-exposed group was US$11 214 before the discount and US$2465 after discount. The negative impact of SHS exposure on health outcomes and healthcare costs escalated as the time horizon increased, suggesting that the adverse impact of SHS exposure may have higher impact on the later part of the lifetime. The result was consistent across a wide range of assumptions. CONCLUSION: Life expectancy might underestimate the impact of SHS exposure on health outcomes, especially if the time horizon of the analysis is not long enough. Early intervention on smoking behaviour could substantially reduce direct healthcare costs and improve quality of life attributable to SHS exposure.

Outcomes of surgical and transcatheter aortic valve replacement in the octogenarians-surgery still the gold standard?

BACKGROUND: Contemporary options for aortic valve replacement (AVR) include transcatheter and surgical approaches (TAVR and SAVR). As evidence accrues for TAVR in high and intermediate risk patients, some clinicians advocate that all patients aged over 80 years should only receive TAVR. Our aim was to investigate the utility of SAVR and minimally invasive AVR (mAVR) among octogenarians in the current era of TAVR. METHODS: From 2002 to 2015, 1,028 octogenarians underwent isolated AVR; 306 TAVR and 722 SAVR, of which 378 patients underwent mAVR. Logistic regression and Cox modeling were used to evaluate overall operative mortality and mid-term survival, respectively. Patients were stratified based on procedural approaches (mAVR or full sternotomy for SAVR, and transfemoral or alternate access for TAVR). Median follow-up was 35 [interquartile range (IQR) 14-65] months. RESULTS: Compared to SAVR patients, TAVR patients were relatively older (86.2 versus 84.2 years) with co-morbidities such as chronic kidney disease (CKD), diabetes mellitus (DM), cerebrovascular disease (CVD), and prior myocardial infarction (MI), all P<0.05. The mean STS-PROM for the TAVR group was statistically higher, 6.81 versus 5.58 for the SAVR group (P<0.001). The median in-hospital LOS was statistically higher for the SAVR group (P<0.05). Cox proportional hazard modeling, adjusted for temporal differences in procedure and patient selection, identified age, New York Heart Association (NYHA) class III/IV, preoperative creatinine, severe chronic lung disease, prior cardiac surgery as significant predictors of decreased survival (all P<0.05), while type of intervention (approach) was non-contributory. Adjusted operative mortality stratified by procedure approaches was similar between full sternotomy SAVR and mAVR, and between alternative access and transfemoral TAVR. CONCLUSIONS: After adjusting for confounders, TAVR (regardless of approach), SAVR, and mAVR had comparable operative mortality and mid-term survival. Treatment decisions should be individualized with consensus from a multi-disciplinary heart team, taking into account patient co morbidities, frailty, and quality of life. We believe certain patient groups will still benefit from SAVR even in this elderly population.