Echocardiographic and Clinical Outcomes in Symptomatic Patients With Less Than Severe Aortic Stenosis After Supra-Annular Self-Expanding Transcatheter Aortic Valve Replacement.

Optimal timing for aortic valve replacement in symptomatic patients with less than severe aortic stenosis (AS) is not well defined. There is limited information on the benefit of valve replacement in these patients. Symptomatic patients with less than severe AS, defined as a mean aortic gradient ≥20 and <40 mm Hg, peak aortic velocity >3 and <4 m/s, and aortic valve area >1.0 and <1.5 cm2, enrolled in the Society for Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy Registry and who underwent attempted supra-annular, self-expanding transcatheter aortic valve replacement (TAVR) were reviewed. Site-reported valve hemodynamics, clinical events, and quality of life metrics were analyzed at 30 days and 1 year after the procedure. A total of 1,067 patients with attempted TAVR (mean age 78.4 ± 8.4 years; Society for Thoracic Surgery score 4.7 ± 3.4%) were found to have symptoms but less than severe AS. From baseline to postprocedure, mean gradient decreased (29.9 ± 4.9 vs 8.4 ± 4.8 mm Hg, p <0.001), and aortic valve area increased (1.2 ± 0.1 vs 2.2 ± 0.7 cm2, p <0.001). Clinical events included 30-day and 1-year all-cause mortality (1.5% and 9.6%), stroke (2.2% and 3.3%), and new pacemaker implantation (18.1% and 20.9%). There were statistically significant improvements in the New York Heart Association functional class and Kansas City Cardiomyopathy Questionnaire at 30 days and 1 year. In conclusion, patients with symptomatic but less than severe AS who underwent supra-annular, self-expanding TAVR experienced improved valve hemodynamics and quality of life measures 1 year after the procedure. Randomized studies of TAVR versus a control arm in symptomatic patients with less than severe AS are ongoing.

Physician assessment of aortic stenosis severity, quantitative parameters, and long-term outcomes: Results from the KP-VALVE project.

BACKGROUND: Contemporary outcomes for aortic stenosis (AS) and the association between physician-assessed AS severity and quantitative parameters is poorly understood. We aimed to evaluate AS natural history, compare outcomes for physicians' AS assessment vs. quantitative parameters, and identify AS parameters with the most explanatory power. METHODS: We ascertained physician-assessed AS severity, echocardiographic parameters, and clinical data for 546,769 patients from 2008-2018, examined multivariable associations of physician-assessed AS severity and number of quantitative severe AS parameters with death, cardiovascular hospitalization, and aortic valve replacement, and estimated the relative contribution of different quantitative AS parameters on outcomes. RESULTS: Among 49,604 AS patients (mean [SD] age 77 [11] years), 17.6% had moderate, 3.6% moderate-severe, and 9.4% severe AS. During median 3.7 [IQR 1.7-6.8] years, physician-assessed AS severity strongly correlated with outcomes, with moderate AS patients tracking closest to mild AS, and moderate-to-severe AS patients more comparable to severe AS. Although the number of quantitative severe AS parameters strongly predicted outcomes (adjusted HR [95% CI] for death 1.40 [1.34-1.46], 1.70 [1.56-1.85], and 1.78 [1.63-1.94] for 1, 2, and 3 parameters, respectively), aortic valve area <1.0 cm2 was the most frequent severe AS parameter, explained the largest relative contribution (67%), and was common in patients classified as moderate (21%) or moderate-severe (56%) AS. CONCLUSIONS: Physician-assessed AS severity predicts outcomes, with cumulative effects for each severe AS parameter. Moderate AS includes a wide spectrum of patients, with discordant AVA <1.0 cm2 being both common and predictive. Better identification of non-classical severe AS phenotypes may improve outcomes.

Outcomes of Adults with Severe Aortic Stenosis Undergoing Urgent or Emergent vs. Elective Transcatheter Aortic Valve Replacement Within an Integrated Health Care Delivery System.

Background: Transcatheter aortic valve replacement (TAVR) may be used to urgently or emergently treat severe aortic stenosis, but outcomes for this high-risk population have not been well-characterized. We sought to describe the incidence, clinical characteristics, and outcomes of patients undergoing urgent or emergent vs. elective TAVR. Methods: We identified all adults who received TAVR for primary aortic stenosis between 2013 and 2019 within an integrated health care delivery system in Northern California. Elective or urgent/emergent procedure status was based on standard Society of Thoracic Surgeons definitions. Data were obtained from electronic health records, the Society of Thoracic Surgeons-American College of Cardiology Transcatheter Valve Therapy Registry, and state/national reporting databases. Logistic regression and Cox proportional hazard models were performed. Results: Among 1564 eligible adults that underwent TAVR, 81 (5.2%) were classified as urgent/emergent. These patients were more likely to have heart failure (63.0% vs. 47.4%), reduced left ventricular ejection fraction (21.0% vs. 11.8%), or a prior aortic valve balloon valvuloplasty (13.6% vs. 5.0%) and experienced higher unadjusted rates of 30-day and 1-year morbidity and mortality. Urgent/emergent TAVR status was independently associated with non-improved quality of life at 30-days (hazard ratio, 4.87; p < 0.01) and acute kidney injury within 1-year post-TAVR (hazard ratio, 2.11; p = 0.01). There was not a significant difference in adjusted 1-year mortality with urgent/emergent TAVR. Conclusions: Urgent/emergent TAVR status was uncommon and associated with high-risk clinical features and higher unadjusted rates of short- and long-term morbidity and mortality. Procedure status may be useful to identify patients less likely to experience significant short term improvement in health-related quality of life post-TAVR.

Temporal trends in the prevalence and severity of aortic stenosis within a contemporary and diverse community-based cohort.

BACKGROUND: Data on the epidemiology of aortic stenosis (AS) are primarily derived from single center experiences and administrative claims data that do not delineate by degree of disease severity. METHODS: An observational cohort study of adults with echocardiographic AS was conducted January 1st, 2013-December 31st, 2019 at an integrated health system. The presence/grade of AS was based on physician interpretation of echocardiograms. RESULTS: A total of 66,992 echocardiogram reports for 37,228 individuals were identified. The mean ± standard deviation (SD) age was 77.5 ± 10.5, 50.5% (N = 18,816) were women, and 67.2% (N = 25,016) were non-Hispanic whites. The age-standardized AS prevalence increased from 589 (95% Confidence Interval [CI] 580-598) to 754 (95% CI 744-764) cases per 100,000 during the study period. The age-standardized AS prevalences were similar in magnitude among non-Hispanic whites (820, 95% CI 806-834), non-Hispanic blacks (728, 95% CI 687-769), and Hispanics (789, 95% CI 759-819) and substantially lower for Asian/Pacific Islanders (511, 95% CI 489-533). Finally, the distribution of AS by degree of severity remained relatively unchanged over time. CONCLUSIONS AND RELEVANCE: The population prevalence of AS has grown considerably over a short timeframe although the distribution of AS severity has remained stable.

Very late stent thrombosis with second generation drug eluting stents compared to bare metal stents: Network meta-analysis of randomized primary percutaneous coronary intervention trials.

BACKGROUND: The relative safety of drug-eluting stents (DES) and bare-metal stents (BMS) in primary percutaneous coronary intervention (PPCI) in ST elevation myocardial infarction (STEMI) continues to be debated. The long-term clinical outcomes between second generation DES and BMS for primary percutaneous coronary intervention (PCI) using network meta-analysis were compared. METHODS: Randomized controlled trials comparing stent types (first generation DES, second generation DES, or BMS) were considered for inclusion. A search strategy used Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion criteria, and sample characteristics were extracted. Network meta-analysis was used to pool direct (comparison of second generation DES to BMS) and indirect evidence (first generation DES with BMS and second generation DES) from the randomized trials. RESULTS: Twelve trials comparing all stents types including 9,673 patients randomly assigned to treatment groups were analyzed. Second generation DES was associated with significantly lower incidence of definite or probable ST (OR 0.59, 95% CI 0.39-0.89), MI (OR 0.59, 95% CI 0.39-0.89), and TVR at 3 years (OR 0.50: 95% CI 0.31-0.81) compared with BMS. In addition, there was a significantly lower incidence of MACE with second generation DES versus BMS (OR 0.54, 95% CI 0.34-0.74) at 3 years. These were driven by a higher rate of TVR, MI and stent thrombosis in the BMS group at 3 years. There was a non-significant reduction in the overall and cardiac mortality [OR 0.83, 95% CI (0.60-1.14), OR 0.88, 95% CI (0.6-1.28)] with the use of second generation DES versus BMS at 3 years. CONCLUSIONS: Network meta-analysis of randomized trials of primary PCI demonstrated lower incidence of MACE, MI, TVR, and stent thrombosis with second generation DES compared with BMS. © 2016 Wiley Periodicals, Inc.

Non-invasive volumetric assessment of aortic atheroma: a core laboratory validation using computed tomography angiography.

Aortic atherosclerosis has been linked with worse peri- and post-procedural outcomes following a range of aortic procedures. Yet, there are currently no standardized methods for non-invasive volumetric pan-aortic plaque assessment. We propose a novel means of more accurately assessing plaque volume across whole aortic segments using computed tomography angiography (CTA) imaging. Sixty patients who underwent CTA prior to trans-catheter aortic valve implantation were included in this analysis. Specialized software analysis (3mensio Vascular™, Pie Medical, Maastricht, Netherlands) was used to reconstruct images using a centerline approach, thus creating true cross-sectional aortic images, akin to those images produced with intravascular ultrasonography. Following aortic segmentation (from the aortic valve to the renal artery origin), atheroma areas were measured across multiple contiguous evenly spaced (10 mm) cross-sections. Percent atheroma volume (PAV), total atheroma volume (TAV) and calcium score were calculated. In our populations (age 79.9 ± 8.5 years, male 52 %, diabetes 27 %, CAD 84 %, PVD 20 %), mean ± SD number of cross sections measured for each patient was 35.1 ± 3.5 sections. Mean aortic PAV and TAV were 33.2 ± 2.51 % and 83,509 ± 17,078 mm(3), respectively. Median (IQR) calcium score was 1.5 (0.7-2.5). Mean (SD) inter-observer coefficient of variation and agreement for plaque area among 4 different analysts was 14.1 (5.4), and the mean (95 % CI) Lin's concordance correlation coefficient was 0.79 (0.62-0.89), effectively simulating a Core Laboratory scenario. We provide an initial validation of cross-sectional volumetric aortic atheroma assessment using CTA. This proposed methodology highlights the potential for utilizing non-invasive aortic plaque imaging for risk prediction across a range of clinical scenarios.

Management of drug eluting stent in-stent restenosis: A systematic review and meta-analysis.

BACKGROUND: The optimal management for coronary drug eluting stent in-stent restenosis (DES ISR) is unclear. We performed a meta-analysis of observational and randomized studies to compare the outcomes of management of DES ISR using DES, drug eluting balloon (DEB), or balloon angioplasty (BA). METHODS: Eligible studies (25 single arm and 13 comparative, including 4 randomized studies with a total of 7,474 patients with DES ISR) were identified using MEDLINE search and proceedings of international meetings. Outcomes studied include major adverse cardiac events (MACE), target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), stent thrombosis (ST), and mortality. Follow-up ranged from 0.5 to 3.5 years (mean 1.4 years). RESULTS: The rate of TLR was significantly lower in the DES (odds ratio [OR] 0.50, 95% confidence interval [CI] 0.36-0.69) and DEB (OR 0.31, 95% CI 0.18-0.55) groups compared to BA. Similarly, TVR rate was significantly lower in the DES (OR 0.55, 95% CI 0.39-0.77) and DEB (OR 0.32, 95% CI 0.18-0.58) groups compared to BA. All other outcomes were similar between the DES/BA and DEB/BA comparisons. TLR was significantly lower in the DES group compared to BA for vessels < or > 2.75 mm. CONCLUSION: Treatment of coronary DES ISR with DES or DEB is associated with a reduction in the risk of TLR and TVR compared to BA alone. The relative risk reduction for TLR with DES is similar to DEB. DEBs have a potential role in the treatment of DES ISR by avoiding placement of another layer of stent. © 2015 Wiley Periodicals, Inc.

Aortic annulus and root characteristics in severe aortic stenosis due to bicuspid aortic valve and tricuspid aortic valves: implications for transcatheter aortic valve therapies.

BACKGROUND: Patients with severe aortic stenosis due to BAV are excluded from transcatheter aortic valve replacement (TAVR) due to concern for asymmetric expansion and valve dysfunction. We sought to characterize the aortic root and annulus in bicuspid aortic valve (BAV) and tricuspid aortic valves (TAV). METHODS AND RESULTS: We identified patients with severe AS who underwent multi-detector computed tomographic (MDCT) imaging prior to surgical aortic valve replacement (SAVR, n = 200) for BAV and TAVR (n = 200) for TAV from 2010 to 2013. The presence of a BAV was confirmed on surgical and pathological review. Annulus measurements of the basal ring (short- and long-axis, area-derived diameter), coronary ostia height, sinus area (SA), sino-tubular junction area (STJ), calcification and eccentricity index (EI, 1-short axis/long axis) were made. Patients with TAV were older (78.8 years vs. 57.8 years, P = 0.04) than those with BAV. The aortic annulus area (5.21 ± 2.1 cm(2) vs. 4.63 ± 2.0 cm(2) , P = 0.0001), sinus of Valsalva diameter (3.7 ± 0.9 cm vs. 3.1 ± 0.1 cm, P = 0.001) and ascending aorta diameter (3.5 ± 0.7 cm vs. 2.97 ± 0.6 cm, P = 0.001) were significantly larger with BAV. Bicuspid aortic annuli were significantly less elliptical (EI, 1.24 ± 0.1 vs. 1.29 ± 0.1, P = 0.006) and more circular (39% vs. 4%, P < 0.001) compared to the TAV annulus. There was more eccentric annular calcification in BAV vs. TAV (68% vs. 32%, P < 0.001). The mean distance from the aortic annulus to the left main coronary ostium was less than the right coronary ostium. Less than 10% of the BAV annuli would not fit a currently available valved stents. CONCLUSION: Bicuspid aortic valves have a larger annulus size, sinus of Valsalva and ascending aorta dimensions. In addition, the BAV aortic annuli appear circular and most will fit currently available commercial valved stents.

Impact of statins and beta-blocker therapy on mortality after coronary artery bypass graft surgery.

BACKGROUND: We conducted a retrospective cohort study of patients after first-time isolated coronary artery bypass graft surgery (CABG) and assessed the impact of a discharge regimen including beta-blockers and statin therapy and their relationship to long-term all cause mortality and major adverse cardiovascular events (MACE). METHODS: We identified patients age >18 years, undergoing first time isolated CABG from 1993 to 2005. Patients were identified using the Cardiovascular Information Registry (CVIR). We collected follow-up information at 30, 60, 90 days and yearly follow-up. The registry is approved for use in research by the institutional review broad. RESULTS: We identified 5,205 patients who underwent single isolated CABG between January 1993 and December 2005. The mean age was 64.5±9.7 years and over 70% were male. There was a significant difference in the low density lipoproteins (LDL) concentration between those with or without statin medications (134±41.9 mg/dL) (no statin) vs. 126±44.8 mg/dL (with statin), P=0.001. A discharge regimen with statin therapy was associated with and overall reduction in 30 day, 1 year and long-term mortality. In addition, overall the triple ischemic endpoint of death, myocardial infarction (MI) and stroke was also significantly lower in the statin vs. no-statin group. In addition, statin and beta-blockers exerted synergistic effect on overall mortality outcomes short-term and in the long-term. We note that the predictors of overall death include no therapy with statin therapy and age [hazard ratios (HR) 1.1, 95% CI: 1.04-1.078, P<0.001] and presence of renal failure (HR 2.0, P=0.005). The estimated 11-year Kaplan Meier curves for mortality between the two groups starts to diverge immediately post discharge after single isolated CABG and continue to diverge through out the follow-up period. CONCLUSIONS: A post-discharge regimen of statins independently reduces overall and 1 year mortality. These results confirm those of earlier studies within a contemporary surgical population and support the current clinical guidelines.

Transient post-operative atrial fibrillation predicts short and long term adverse events following CABG.

OBJECTIVE: To assess the relationship between the development of transient post-operative atrial fibrillation (TPOAF) following coronary artery bypass graft (CABG) surgery and risk of long-term mortality. BACKGROUND: Atrial fibrillation (AF) following CABG is common and associated with increased morbidity and mortality in the perioperative period. However the impact of TPOAF and its management on long-term morbidity and mortality in patients undergoing first time, isolated CABG surgery remains unclear. METHODS: The Cleveland Clinic Cardiovascular Information Registry was used to identify 5,205 consecutive patients who underwent CABG between January 1993 and December 2005. Patients with TPOAF (n=1,490) were compared to those without post-operative AF (n=3,645) for the endpoints of death, myocardial infarction (MI), or stroke at 1 year. RESULTS: Overall rates of 1-year mortality, MI and stroke were 3.7%, 0.8%, and 2.6%, respectively. Patients with TPOAF had an increased risk of death at 1 year as compared to patients without POAF (6.4% vs. 2.7%; P<0.001), but there was not an increased risk of stroke or MI. Multivariate analysis identified TPOAF as an independent predictor of death at 1 year (HR 1.89, 95% CI, 1.42-2.53; P<0.001). After propensity matching, patients who developed TPOAF experienced a significantly increased risk of death compared with those without TPOAF (HR 1.96, 95% CI, 1.34-2.86; P<0.001). CONCLUSIONS: In patients undergoing first time, isolated CABG, the presence of TPOAF identifies a subgroup of patients at increased risk for all-cause mortality. Future prospective studies to determine potential beneficial interventions in this large population are warranted.