The Impact of Frailty on Outcomes of Proximal Aortic Aneurysm Surgery: A Nationwide Analysis.

(1) Background: This study examines frailty's impact on proximal aortic surgery outcomes. (2) Methods: All patients with a thoracic aortic aneurysm who underwent aortic root, ascending aorta, or arch surgery from the 2016-2017 National Inpatient Sample were included. Frailty was defined by the Adjusted Clinical Groups Frailty Indicator. Outcomes of interest included in-hospital mortality and a composite of death, stroke, acute kidney injury (AKI), and major bleeding (MACE). (3) Results: Among 5745 patients, 405 (7.0%) met frailty criteria. Frail patients were older, with higher rates of chronic pulmonary disease, diabetes, and chronic kidney disease. There was no difference in in-hospital death (4.9% vs. 2.4%, p = 0.169); however, the frail group exhibited higher rates of stroke and AKI. Frail patients had a longer length of stay (17 vs. 8 days), and higher rates of non-home discharge (74.1% vs. 54.3%) than non-frail patients (both p < 0.001). Sensitivity analysis confirmed increased morbidity and mortality in frail individuals. After adjusting for patient comorbidities and hospital characteristics, frailty independently predicted MACE (OR 4.29 [1.88-9.78], p = 0.001), while age alone did not (OR 1.00 [0.99-1.02], p = 0.568). Urban teaching center status predicted a lower risk of MACE (OR 0.27 [0.08-0.94], p = 0.039). (4) Conclusions: Frailty is associated with increased morbidity in proximal aortic surgery and is a more significant predictor of mortality than age. Coordinated treatment in urban institutions may enhance outcomes for this high-risk group.

Evolving Concept of Aortic Valve Replacement in Asymptomatic Patients With Severe Aortic Stenosis.

BACKGROUND: Surgical treatment of asymptomatic severe aortic stenosis (AS) has been gaining attention ever since the results of the Early Surgery Versus Conventional Treatment in Very Severe Aortic Stenosis (RECOVERY) and Aortic Valve replacement versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR) trials showed survival benefits with early surgical aortic valve replacement (SAVR). This study analyzed the long-term clinical and echocardiographic outcomes of SAVR in asymptomatic severe AS. METHODS: Between 2002 and 2020, 272 patients with asymptomatic severe AS and a left ventricular ejection fraction ≥50% underwent SAVR with or without concomitant aortic surgery and met the study criteria. The median follow-up was 8.5 years (interquartile range, 6-12.8 years), for a total of 2584 patient-years. The time course of the left ventricular mass index (LVMI) and the average E/E' (ratio of the Doppler-derived E wave to the tissue Doppler-derived E' wave) were assessed using 594 postoperative echocardiograms. The association of preoperative LVMI and average E/E' with survival was assessed using Cox proportional hazards. RESULTS: There was no operative mortality. On longitudinal analyses, LVMI improved in patients who presented with moderate or severe preoperative left ventricular hypertrophy (LVH). However, after the early decline in average E/E', there was a late increase to greater than upper limit normal, particularly in patients with a preoperative average E/E'≥14. Postoperative survival was 100%, 94%, 84%, and 76% at 1, 5, 10, and 15 years, respectively, comparable to age- and sex-matched expected survival on the basis of the US general population. On adjusted Cox survival analysis, only moderate to severe LVH was associated with a survival penalty (hazard ratio], 2.32; 95% CI, 1.02-5.27; P = .045). CONCLUSIONS: In asymptomatic patients with AS, SAVR restores survival and improves LVH, but patients with diastolic dysfunction are left with persistent dysfunction. Presentation with moderate or severe LVH at the time of surgery translated to a survival penalty. This observational study supports early SAVR in this population before development of LVH, although further investigation is needed.

National trends in utilization of transatrial transcatheter mitral valve replacement and postoperative outcomes.

OBJECTIVE: Transatrial transcatheter mitral valve replacement reduces complexity during mitral valve replacements involving high-risk patients with mitral annular calcification. This study examines trends in transatrial transcatheter mitral valve replacement use and outcomes. METHODS: Patients in the Society of Thoracic Surgeons database from 2014 to 2021 with mitral annular calcification undergoing transatrial transcatheter mitral valve replacement were included. Exclusion criteria were hypertrophic cardiomyopathy, congenital mitral valve disease, ventricular assist device placement, or prior mitral valve surgery. Primary outcomes were operative mortality and major adverse cardiac events compared between the Early (2014-2017, N = 71) and Recent (2018-2021, N = 151) eras. Parsimonious multivariable regression assessed select possible confounders for trends in major adverse cardiac events. RESULTS: Overall, 222 transatrial transcatheter mitral valve replacements at 104 hospitals were identified. Annual volume increased from 6 in 2014 to 43 in 2021. Median hospital volume was 1, maximum hospital volume was 17, and 10 or more replacements were performed at 4 hospitals. Mortality and major adverse cardiac events occurred in 10.4% and 22.5% of patients, respectively. Compared with the Early era patients, Recent era patients were more often elective (79.5% vs 64.8%) and were approached via sternotomy (90.1% vs 80.3%, all P < .05). Despite similar predicted risk of mortality (9.6% ± 11.1% vs 11.0% ± 6.0%; P = .61), Recent patients had reduced mortality (3.3% vs 25.4%, P < .001) and major adverse cardiac events (18.5% vs 31.0%; P = .057). On univariate and multivariable analyses, the Recent surgical era was significantly associated with lower mortality (0.10 [0.04-0.29]; P < .001) and lower major adverse cardiac events (0.48 [0.25-0.94]; P = .032), respectively. There were no preoperative characteristics that were significant confounders for the difference in major adverse cardiac events. CONCLUSIONS: Mortality and major adverse cardiac events after transatrial transcatheter mitral valve replacement have decreased significantly in the contemporary era independent of changes in major patient and operative characteristics. Transatrial transcatheter mitral valve replacement will have a future role in patients with mitral annular calcification.

Calpain inhibition decreases oxidative stress via mitochondrial regulation in a swine model of chronic myocardial ischemia.

INTRODUCTION: Calpain overexpression is implicated in mitochondrial damage leading to tissue oxidative stress and myocardial ischemic injury. The aim of this study was to determine the effects of calpain inhibition (CI) on mitochondrial impairment and oxidative stress in a swine model of chronic myocardial ischemia and metabolic syndrome. METHODS: Yorkshire swine were fed a high-fat diet for 4 weeks to induce metabolic syndrome then underwent placement of an ameroid constrictor to the left circumflex artery. Three weeks later, animals received: no drug (control, "CON"; n= 7); a low-dose calpain inhibitor (0.12 mg/kg; "LCI", n= 7); or high-dose calpain inhibitor (0.25 mg/kg; "HCI", n=7). Treatment continued for 5 weeks, followed by tissue harvest. Cardiac tissue was assayed for protein carbonyl content, as well as antioxidant and mitochondrial protein expression. Reactive oxygen species (ROS) and mitochondrial respiration was measured in H9c2 cells following exposure to normoxia or hypoxia (1%) for 24 h with or without CI. RESULTS: In ischemic myocardial tissue, CI was associated with decreased total oxidative stress compared to control. CI was also associated with increased expression of mitochondrial proteins superoxide dismutase 1, SDHA, and pyruvate dehydrogenase compared to control. 100 nM of calpain inhibitor decreased ROS levels and respiration in both normoxic and hypoxic H9c2 cardiomyoblasts. CONCLUSIONS: In the setting of metabolic syndrome, CI improves oxidative stress in chronically ischemic myocardial tissue. Decreased oxidative stress may be via modulation of mitochondrial proteins involved in free radical scavenging and production.

Apixaban or Warfarin in Patients with an On-X Mechanical Aortic Valve.

Apixaban, Warfarin, and On-X Mechanical Aortic ValvesAlthough vitamin K antagonists are the only oral anticoagulants approved with mechanical heart valves, this trial examined whether apixaban could be safely used in patients with an On-X mechanical aortic valve. A total of 863 such patients were assigned apixaban 5 mg twice daily or warfarin (target international normalized ratio 2.0 to 3.0). A total of 20 thrombotic events occurred in the apixaban group (4.2%/patient-year) and 6 events in the warfarin group (1.3%/patient-year). Major bleeding rates were 3.6%/patient-year with apixaban and 4.5%/patient-year with warfarin.

Aortic root management in acute type A aortic dissection: A nationwide analysis.

OBJECTIVE: Acute type A aortic dissection (ATAAD) is a life-threatening condition and surgical repair often includes aortic valve replacement (AVR). Aortic valve repair (AVr) is increasingly being reported with favorable outcomes from single-center experiences. This study examined national trends and outcomes of AVr in patients with ATAAD. METHODS: Adults with a primary diagnosis of acute thoracic aortic dissection who underwent proximal aortic surgery from January 2016 to December 2017 were obtained from the National Inpatient Sample. Patients were stratified into an isolated aortic surgery group (no aortic valve procedure), concomitant AVR, or concomitant AVr groups. The primary outcome was in-hospital mortality and secondary outcomes included stroke, acute kidney injury, heart block, and bleeding. Propensity score matching was used to address patient and hospital-level confounders between AVR and AVr groups. RESULTS: In total, 5115 patients underwent surgery for ATAAD and were included. Overall, 3220 (63%) underwent isolated ATAAD repair, while 1120 (22%) had concomitant AVR, and 775 (15%) had concomitant AVr. In 455 propensity-matched pairs, there was no difference in mortality or stroke between AVr and AVR groups, however, heart block (1.1% vs. 7.5%, p < .001) and bleeding (65.9% vs. 81.3%, p < .001) were significantly less common among those who underwent AVr. Patients who underwent AVr had shortest LOS (11.9 vs. 13.5 days, p < .001). There were no differences in outcomes of AVr in ATAAD based on hospital size or teaching status. CONCLUSION: In selected patients, AVr is being performed safely in the setting of ATAAD with mortality and composite outcomes comparable to AVR.

Stent Graft-induced Aortic Wall Injury: Incidence, Risk Factors, and Outcomes.

BACKGROUND: Stent graft-induced new entry has been described in thoracic endovascular aortic repair for aortic dissection. The incidence of stent graft-induced aortic wall injury (SAWI) related to iatrogenic injury in nondissections is incompletely described. We describe incidence, risk factors, and outcomes of SAWI. METHODS: All post-thoracic endovascular aortic repair computed tomography angiograms (January 2005 to December 2018) were reviewed for radiographic evidence of SAWI. Endograft-induced aortic dissections were likewise considered SAWI. Patient characteristics, time to SAWI, and need for reintervention were noted. Cox proportional hazards modeling was used to identify risk factors for SAWI. RESULTS: Within the study cohort (n = 430), 38 patients (9%) had SAWI during a median follow-up of 2.3 years (interquartile range, 4.8); 42% (n = 16) were proximal, 53% (n = 20) distal, and 5% (n = 2) both proximal and distal. Nine (23%) were distal intimal flap injuries in dissection cases, thus subclassifying them as stent graft-induced new entry. Twenty-nine percent of SAWI (n = 11) required reintervention. Of these, 45% (n = 5) were open, and 55% (n = 6) were endovascular. Thoracic endovascular aortic repair for acute dissection had a higher incidence of SAWI development (hazard ratio 4.6; 95% confidence interval, 2.4 to 9; P < .001) as compared with other indications. Use of devices with proximal bare springs or barbs was also associated with increased SAWI incidence (hazard ratio 5.3; 95% confidence interval, 2.6 to 11.0; P < .001). CONCLUSIONS: The rate of SAWI after thoracic endovascular aortic repair is low (9%), but nearly one third will require reintervention. Thoracic endovascular aortic repair in the setting of acute dissection and use of devices with proximal bare springs or barbs were associated with an increased incidence of SAWI.

Calpain inhibition decreases myocardial fibrosis in chronically ischemic hypercholesterolemic swine.

OBJECTIVES: Calpain activation during ischemia is known to play critical roles in myocardial remodeling. We hypothesize that calpain inhibition (CI) may serve to reverse and/or prevent fibrosis in chronically ischemic myocardium. METHODS: Yorkshire swine were fed a high-cholesterol diet for 4 weeks followed by placement of an ameroid constrictor on the left circumflex artery to induce myocardial ischemia. 3 weeks later, animals received either: no drug; high-cholesterol control group (CON; n = 8); low-dose CI (0.12 mg/kg; LCI, n = 9); or high-dose CI (0.25 mg/kg; HCI, n = 8). The high-cholesterol diet and CI were continued for 5 weeks, after which myocardial tissue was harvested. Tissue samples were analyzed by western blot for changes in protein content. RESULTS: In the setting of hypercholesterolemia and chronic myocardial ischemia, CI decreased the expression of collagen in ischemic and nonischemic myocardial tissue. This reduced collagen content was associated with a corresponding decrease in Jak/STAT/MCP-1 signaling pathway, suggesting a role for Jak 2 signaling in calpain activity. CI also decreases the expression of focal adhesion proteins (vinculin) and stabilizes the expression of cytoskeletal and structural proteins (N-cadherin, α-fodrin, desmin, vimentin, filamin, troponin-I). CI had no significant effect on metabolic and hemodynamic parameters. CONCLUSIONS: Calpain inhibition may be a beneficial medical therapy to decrease collagen formation in patients with coronary artery disease and associated comorbidities.

All-cause Readmission after Transcatheter Aortic Valve Replacement in a Community Hospital - Long Term Follow-up.

BACKGROUND: Post-procedure readmissions are associated with lower quality of life and increased economic burden. The study aimed to identify predictors for long-term all-cause readmissions in patients who underwent transcatheter aortic valve replacement (TAVR) in a community hospital. METHODS: A Historical cohort study of all adults who underwent TAVR at Cape-Cod hospital between June 2015 and December 2017 was performed and data on readmissions was collected up-to May 2020 (median follow up of 3.3 years). Pre-procedure, procedure and in-hospital post-procedure parameters were collected. Readmission rate was evaluated, and univariate and multivariable analyses were applied to identify predictors for readmission. RESULTS: The study included 262 patients (mean age 83.7±7.9 years, 59.9% males). The median Society of Thoracic Surgeons (STS) probability of mortality (PROM) score was 4.9 (IQR, 3.1-7.9). Overall, 120 patients were readmitted. Ten percent were readmitted within 1-month, 20.8% within 3-months, 32.0% within 6-months and 44.5% within 1-year. New readmissions after 1-year were rare. STS PROM 5% or above (HR 1.50, p = 0.039), pre-procedure anemia (HR 1.63, p = 0.034), severely decreased pre-procedure renal function (HR 1.93, p = 0.040) and procedural complication (HR 1.65, p = 0.013) were independent predictors for all-cause readmission. CONCLUSIONS: Elevated procedural risk, anemia, renal dysfunction and procedural complication are important predictors for readmission. Pre-procedure and ongoing treatment of the patient's background diseases and completion of treatment for complications prior to discharge may contribute to a reduction in the rate of readmissions.

A step-by-step guide to transseptal valve-in-valve transcatheter mitral valve replacement.

With the recent success of transcatheter aortic valve replacement (TAVR), transcatheter options for the management of mitral valve pathology have also gained considerable attention. Valve-in-valve (ViV) transcatheter mitral valve replacement (TMVR) is one such technique that has emerged as a safe and effective therapeutic option for patients with degenerated mitral valve bioprostheses at high-risk for repeat surgical mitral valve replacement. Several access strategies, including trans-apical, transseptal, trans-jugular, and trans-atrial access have been described for ViV-TMVR. Initial experiences were performed primarily via a trans-apical approach through a left mini-thoracotomy because it offers direct access and coaxial device alignment. With the advancements in TMVR technology, such as the development of smaller delivery catheters with high flexure capabilities, the transseptal approach via the femoral vein has emerged as the preferred option. This technique offers the advantages of a totally percutaneous approach, avoids the need to enter the thoracic cavity or pericardial space, and provides superior outcomes compared to a trans-apical approach. In this review, we outline key aspects of patient selection, imaging, procedural techniques, and examine contemporary clinical outcomes of transseptal ViV-TMVR.

Long-term Outcomes of Aortic Valve Replacement With Aortic Homograft: 27 Years Experience.

BACKGROUND: Aortic homografts have been used in young patients requiring aortic valve replacement. Currently, these grafts are generally reserved for aortic valve endocarditis with or without root abscess; however, longitudinal data are lacking. Our aim was to assess the long-term safety and durability of homograft implantation. METHODS: All adult patients undergoing aortic homograft implantation at a single institution from 1992 to 2019 were included. Outcomes of interest included all-cause mortality and aortic valve reoperation, studied over a median follow-up duration of 19 years. RESULTS: In all, 252 patients with a mean age of 49 years were included. Infective endocarditis was the primary indication for surgery in 95 patients (38%). The endocarditis group, compared with the no-endocarditis group, had a higher prevalence of New York Heart Association class III-IV (56% vs 26%), chronic kidney disease (22% vs 1%), prior cardiac surgery (40% vs 10%), and emergency status (7% vs 0%; all P < .001). Operative mortality was higher among endocarditis patients (16% vs 0.6%, P < .001), which persisted after risk adjustment. Among patients who survived to discharge, however, there was no difference in long-term survival between the endocarditis group and no-endocarditis group. Overall survival and freedom from reoperation were 88.3% and 80% at 15 years and 87.2% and 78% at 25 years, respectively. Indications for reoperation included structural valve deterioration (83%), endocarditis (12%), and mitral valve disease (5%). Reoperative mortality occurred in 2 patients (4.9%). CONCLUSIONS: Aortic homografts are associated with good long-term survival and admissible freedom from reoperation. Operative mortality is high among patients with endocarditis; however, for those who survive to discharge, long-term survival and durability are the same as for patients without endocarditis.

When to Consider Deferral of Surgery in Acute Type A Aortic Dissection: A Review.

BACKGROUND: Acute type A aortic dissection (ATAAD) is a surgical emergency with an operative mortality of up to 30%, a rate that has not changed meaningfully in more than 2 decades. A growing body of research has highlighted several comorbidities and presenting factors in which delay or permanent deferral of surgery may be considered; however, modern comprehensive summative reviews are lacking. The urgency and timing of this review are underscored by significant challenges in resource use posed by the coronavirus disease 2019 (COVID-19) pandemic. This review provides an update on the current understanding of risk assessment, surgical candidacy, and operative timing in patients with ATAAD. METHODS: A literature search was conducted through PubMed and Embase databases to identify relevant studies relating to risk assessment in ATAAD. Articles were selected by group consensus on the basis of quality and relevance. RESULTS: Several patient factors have been identified that increase risk in ATAAD repair. In particular, frailty, advanced age, previous cardiac surgery, and use of novel anticoagulant medications have been studied. The understanding of malperfusion syndromes has also expanded significantly, including recommendations for surgical delay. Finally, approaches to triage have been significantly influenced by resource limitations related to the ongoing COVID-19 pandemic. Although medical management remains a reasonable option in carefully selected patients at prohibitive risk for open surgery, endovascular therapies for treatment of ATAAD are rapidly evolving. CONCLUSIONS: Early surgical repair remains the preferred treatment for most patients with ATAAD. However, improvements in risk stratification should guide appropriate delay or permanent deferral of surgery in select individuals.