Dysfunction of vessel endothelium is the first step in a complex and multi-faceted process that eventually leads to initiation of the plaque, formation of atherosclerotic lesions and their ...complications. The extremely fine-regulated endothelium is the gatekeeper of vascular health, and has been the target of a substantial amount of research.
This review examines some of the most common associations between therapies of cardiovascular disease and the endothelium, and summarizes the direction of research that may set the stage for one or more interventions targeted to repair damaged and/or dysfunctional endothelium. Expert commentary: Routine treatment of cardiovascular disease has frequently been shown to have a positive effect on the vascular endothelium. The big question - whether the impact is due to a direct pharmacological effect or whether the function of the endothelium improves as a result of a general improvement in the underlying disease state, is still largely unanswered.
Ischemic preconditioning (IPC) is a mechanism protecting tissues from injury during ischemia and reperfusion. Remote IPC (RIPC) can be elicited by applying brief periods of ischemia to tissues with ...ischemic tolerance, thus protecting vital organs more susceptible to ischemic damage. Using a porcine model, we determined whether RIPC of the limb is protective against brain injury caused by hypothermic circulatory arrest (HCA).
Twelve piglets were randomized to control and RIPC groups. RIPC was induced in advance of cardiopulmonary bypass by 4 cycles of 5 minutes of ischemia of the hind limb. All animals underwent cardiopulmonary bypass followed by 60 minutes of HCA at 18°C. Brain metabolism and electroencephalographic activity were monitored for 8 hours after HCA. Assessment of neurological status was performed for a week postoperatively. Finally, brain tissue was harvested for histopathological analysis. Study groups were balanced for baseline and intraoperative parameters. Brain lactate concentration was significantly lower (P<0.0001, ANOVA) and recovery of electroencephalographic activity faster (P<0.05, ANOVA) in the RIPC group. RIPC had a beneficial effect on neurological function during the 7-day follow-up (behavioral score; P<0.0001 versus control, ANOVA). Histopathological analysis demonstrated a significant reduction in cerebral injury in RIPC animals (injury score; mean interquartile range: control 5.8 3.8 to 7.5 versus RIPC 1.5 0.5 to 2.5, P<0.001, t test).
These data demonstrate that RIPC protects the brain against HCA-induced injury, resulting in accelerated recovery of neurological function. RIPC might be neuroprotective in patients undergoing surgery with HCA and improve long-term outcomes. Clinical trials to test this hypothesis are warranted.
Abstract Background A minimalist approach for transcatheter aortic valve replacement (MA-TAVR) utilizing transfemoral access under conscious sedation and transthoracic echocardiography is increasing ...in popularity. This relatively novel technique may necessitate a learning period to achieve proficiency in performing a successful and safe procedure. This report evaluates our MA-TAVR cohort with specific characterization between our early, midterm, and recent experience. Methods We retrospectively reviewed 151 consecutive patients who underwent MA-TAVR with surgeons and interventionists equally as primary operator at Emory University between May 2012 and July 2014. Our institution had performed 300 TAVR procedures before implementation of MA-TAVR. Patient characteristics and early outcomes were compared using Valve Academic Research Consortium 2 definitions among 3 groups: group 1 included the first 50 patients, group 2 included patients 51 to 100, and group 3 included patients 101 to 151. Results Median age for all patients was 84 years and similar among groups. The majority of patients were men (56%) and the median ejection fraction for all patients was 55% (interquartile range, 38.0%-60.0%). The majority of patients were high-risk surgical candidates with a median Society of Thoracic Surgeons Predicted Risk of Mortality of 10.0% and similar among groups. The overall major stroke rate was 3.3%, major vascular complications occurred in 3% of patients, and greater-than-mild paravalvular leak rate was 7%. In-hospital mortality and morbidity were similar among all 3 groups. Conclusions In a high-volume TAVR center, transition to MA-TAVR is feasible with acceptable outcomes and a diminutive procedural learning curve. We advocate for TAVR centers to actively pursue the minimalist technique with equal representation by cardiologists and surgeons.
Patient characteristics and procedural outcomes from nontransfemoral (non-TF) transcatheter aortic valve replacement (TAVR) in high-risk or inoperable patients with aortic stenosis have been ...incompletely reported. The purpose of this study was to compare outcomes with non-TF TAVR access techniques including transapical (TA), transaortic (TAo), and transcarotid (TC) TAVR with a balloon-expandable valve.
A retrospective review was performed of all patients undergoing TA, TAo, and TC TAVR from 2007 to 2013 at Emory University. Preoperative risk factors and postoperative outcomes were evaluated using Valve Academic Research Consortium-2 definitions.
Of 469 patients undergoing TAVR during that period at our institution, 139 underwent TA TAVR, 35 had Tao TAVR, and 11 had TC TAVR. Patients undergoing TC TAVR were younger than those undergoing TA TAVR and TAo TAVR (mean ages: TC, 68.9 ± 23.6 years; TA, 81.3 ± 7.7 years; Tao, 83.8 ± 8.3 years; p = 0.017). Most patients undergoing TAo TAVR were women (82.9%), whereas patients undergoing TA TAVR were more likely to be men (62.6%). Slightly more than half of patients undergoing TA TAVR (54.7%) and TC (54.6%) TAVR had undergone previous coronary artery bypass grafting (CABG), whereas no patients underwent TAo TAVR (0%). There was no preoperative difference in ejection fraction, New York Heart Association classification, significant chronic obstructive pulmonary disease, and The Society of Thoracic Surgeons predicted risk of mortality between TA TAVR, Tao TAVR, and TC TAVR, respectively. Average postoperative length of stay was 9 to 11 days and was similar among groups (p = 0.22). There were 13 (9.4%) TA TAVR operative deaths and 4 (11.4%) operative deaths in the TAo TAVR group. There were no deaths in the TC TAVR group.
In high-risk and inoperable patients who are not candidates for TF TAVR, careful selection of alternative access options can lead to excellent and comparable postoperative outcomes.
When transcatheter aortic valve replacement (TAVR) cannot be carried out through transfemoral access, alternative access TAVR is indicated. The purpose of this study was to explore inhospital and ...1-year outcomes of patients undergoing alternative access TAVR through the transapical (TA) or transaortic (TAo) techniques in the United States.
Clinical records of 4,953 patients undergoing TA (n = 4,085) or TAo (n = 868) TAVR from 2011 to 2014 in The Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapy Registry were linked to Centers for Medicare and Medicaid Services hospital claims. Inhospital and 1-year clinical outcomes were stratified by operative risk; and the risk-adjusted association between access route and mortality, stroke, and heart failure repeat hospitalization was explored.
Mean age for all patients was 82.8 ± 6.8 years. The median STS predicted risk of mortality was significantly higher among patients undergoing TAo (8.8 versus 7.4, p < 0.001). When compared with TA, TAo was associated with an increased risk of unadjusted 30-day mortality (10.3% versus 8.8%) and 1-year mortality (30.3% versus 25.6%, p = 0.006). There were no significant differences between TAo and TA for inhospital stroke rate (2.2%), major vascular complications (0.3%), and 1-year heart failure rehospitalizations (15.7%). Examination of high-risk and inoperable subgroups showed that 1-year mortality was significantly higher for TAo patients classified as inoperable (p = 0.012).
Patients undergoing TAo TAVR are older, more likely female, and have significantly higher STS predicted risk of mortality scores than patients operated on by TA access. There were no risk-adjusted differences between TA and TAo access in mortality, stroke, or readmission rates as long as 1 year after TAVR.
Although preoperative renal dysfunction (RD) is associated with increased mortality and morbidity after surgical aortic valve replacement, its impact on clinical outcomes after transcatheter aortic ...valve replacement (TAVR) is less defined.
TAVR patients in the PARTNER (Placement of Aortic Transcatheter Valves) trial with a calculable glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease equation were included. Patients were divided into three groups: GFR >60 mL/min (none/mild RD), GFR 31 to 60 mL/min (moderate RD), and GFR ≤30 mL/min (severe RD). Operative characteristics and clinical outcomes were analyzed. Cox regression models were used to determine multivariable predictors of 1-year all-cause mortality.
A total of 2,531 inoperable or high surgical risk patients from the PARTNER trial and continued access registries had a calculable GFR level: 767 (30%) had normal renal function or mild RD, 1,473 (58%) had moderate RD, and 291 (12%) presented with severe RD. The mean Society of Thoracic Surgeons Predicted Risk of Mortality for the cohort was 11.5%, and it was highest in those with severe RD (13.8%). Patients with severe RD were more often women with a higher prevalence of diabetes. Patients with severe RD had the highest incidence of 30-day and 1-year all-cause mortality and rehospitalization. The 30-day rate of death from any cause was 10.7% in the severe RD group versus 6.0% in the moderate and mild RD groups (p = 0.01). The 1-year rate of death from any cause was 34.4% in the severe RD group versus 21.5% in the moderate RD and 20.8% in the none/mild RD groups (adjusted hazard ratio HR 2.24, p < 0.0001 for severe versus none/mild; adjusted HR 1.14, p = 0.24 for severe versus moderate). Other significant predictors of 1-year all-cause mortality included lower body mass index, frailty, the transapical approach, a lower ejection fraction, oxygen-dependent chronic obstructive pulmonary disease, liver disease, and male sex.
Preoperative severe RD is a significant predictor for 1-year mortality in TAVR patients. Careful risk stratification by the heart team is required in patients with severe preprocedural RD.
Screening for internal carotid artery stenosis (ICAS) with Doppler ultrasound is commonly used before cardiovascular surgery. Nevertheless, the relationship between ICAS and procedure-related stroke ...in isolated aortic valve replacement is unclear.
We retrospectively reviewed patients with artery stenosis who underwent ICAS screening before surgical (SAVR) or transcatheter aortic valve replacement (TAVR) between January 2007 and August 2014. Logistic regression models were used to determine the relation between post-procedure stroke and total (sum of left and right ICAS) and maximal unilateral ICAS. Age, sex, history of atrial fibrillation, cerebrovascular disease and diabetes, left ventricular ejection fraction, and procedure type were considered as covariates. Two-subgroup analyses were performed in patients who underwent TAVR and SAVR, adjusting for procedure specific details.
A total of 996 patients underwent ICAS screening before TAVR (n = 467) or SAVR (n = 529). The prevalence of at least ≥70% ICAS was 5.2% (n = 52) and incidence of 30-day stroke was 3.4% (n = 34). Eight patients who underwent carotid intervention before valve replacement and 6 patients with poor Doppler images were excluded from the final analysis. We found no statistically significant association between stroke and either the total or maximal unilateral ICAS for all patients (p = 0.13 and p = 0.39, respectively) or those undergoing TAVR (p = 0.27 and p = 0.63, respectively) or SAVR (p = 0.21 and p = 0.36, respectively).
We found no statistically significant association between ICAS severity procedure-related stroke after aortic valve replacement. This suggests that universal carotid Doppler screening before isolated TAVR or SAVR is unnecessary.
Transcatheter aortic valve replacement (TAVR) may offer extreme-aged patients a treatment alternative to surgical aortic valve replacement (SAVR). The objective of this study was to describe outcomes ...of TAVR in nonagenarians using transfemoral and alternative access techniques.
In a retrospective review, we found 95 nonagenarians who underwent TAVR from September 2007 through February 2014 at Emory University using a balloon expandable valve: transfemoral (n = 66), transapical (n = 14), transaortic (n = 14), and transcarotid (n = 1). Morbidity and 30-day and midterm mortality were assessed. Kaplan-Meier plots were used to determine midterm survival rates.
The mean age of the patients was 91.8 ± 1.8 years, and 49 (52%) were female. Postoperative morbidity included 1 patient (1%) each with stroke, myocardial infarction, pneumonia, and renal failure. The mean postoperative length of stay was 6.8 ± 5.1 days for all patients. Overall 30-day mortality was 3.2%, much less than The Society of Thoracic Surgeons predicted risk of mortality of 14.5% ± 7.3%. There were no deaths in the transfemoral patients, but there were 2 transapical deaths (14.3%) and 1 transaortic death (7.1%). The Kaplan-Meier estimate of median survival was 2.6 years.
Extreme-aged nonagenarian patients may have excellent outcomes from TAVR at 30-day and midterm follow-up. Alternative access TAVR is associated with higher morbidity and mortality than transfemoral TAVR. Referral for TAVR of nonagenarians should not be precluded based on age alone.
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