Impact of preprocedural left ventricle hypertrophy and geometrical patterns on mortality following TAVR.

BACKGROUND: In contrast to surgical aortic valve replacement, left ventricle (LV) hypertrophy (LVH) had not been clearly associated with mortality following transcatheter aortic valve replacement (TAVR). METHODS: We performed a retrospective analysis of patients enrolled in the Israeli multicenter TAVR registry for whom preprocedural LV mass index (LVMI) data were available. Patients were divided into categories according to LVMI: normal LVMI and mild, moderate, and severe LVH. Mild LVH was regarded as the reference group. Additionally, LV geometry patterns were examined (concentric and eccentric LVH, and concentric remodeling). RESULTS: The cohort consisted of 1,559 patients, 46.5% male, with a mean age of 82.2 (±6.8) years and mean LVMI of 121 (±29) g/m2. Rates of normal LVMI and mild, moderate, and severe LVH were 31% (n = 485), 21% (n = 322), 18% (n = 279), and 30% (n = 475), respectively. Three-year mortality rates for normal LVMI and mild, moderate, and severe LVH were 19.8%, 18.3%, 23.7%, and 24.4%, respectively. Compared to mild LVH, moderate LVH and severe LVH were independently associated with an increased risk for all-cause mortality (hazard ratio [HR] 1.58, 95% CI 1.15-2.18, P = .005; HR 1.46, 95% CI 1.1-1.95, P = .009; respectively). Concentric LVH was independently associated with a decreased risk for mortality compared to normal LV geometry (HR 0.75, 95% CI 0.63-0.89, P = .001). Compared to concentric LVH, eccentric LVH was independently associated with a 33% increased risk for mortality (HR 1.33, 95% CI 1.11-1.60, P = .002). CONCLUSIONS: Mild concentric LVH confers a protective effect among patients with severe aortic stenosis undergoing TAVR. However, hypertrophy becomes maladaptive, and an increased baseline LVMI, eccentric pattern particularly, may be associated with all-cause mortality in this population.

Safety outcomes of new versus old generation transcatheter aortic valves.

OBJECTIVE: To compare procedural outcomes of transcatheter aortic valve implantation (TAVI) patients who were implanted with older versus newer generation valves. BACKGROUND: The current evidence base for improved safety of the newer commercially available TAVI valves is limited. METHODS: A retrospective analysis of the Israeli multicenter TAVI registry was performed. Patients were stratified by valve generation of four commercially available devices: Edwards Sapien (ESX) Edwards Sapien S3 (ES3), Medtronic CoreValve (MCV), and Medtronic Evolut R (MER). RESULTS: The cohort consisted of 737 patients with new generation valves (NGVs; ES3 n = 223; MER n = 514) and 1,869 with old generation valves (OGVs; MCV n = 1,181; ESX n = 688). Device success rates were significantly higher in NGV (97.5 versus 95.4%), with less post-procedural paravalvular leak (3 versus 5.8%), and valve mal-positioning (1.2 versus 3.4%); all P-values<0.05. There were no differences in rates of permanent pacemaker implantation, stroke or acute kidney injury (AKI) of any stage between the groups, although stage ≥2 AKI was more prevalent in NGV. After adjustment to significant differences in baseline patient and procedural characteristics, device success was higher (OR 1.86, 95% confidence interval (CI) 1.09-3.18, P = 0.023) and the 1-month safety outcome was significantly lower (OR 0.72, 95% CI 0.55-0.96, P = 0.025) for NGV. Device success was driven mainly by improved rates of PVL of ES3, while the safety outcome was mainly driven by improved rates of life-threatening bleeding and valve mal-positioning of MER. CONCLUSION: As compared to OGV, use of NGV for TAVI was associated with higher rates of device success and lower rates of adverse events.

Validation of cardiac damage classification and addition of albumin in a large cohort of patients undergoing transcatheter aortic valve replacement.

AIMS: We aimed to validate a new scoring system based on extent of cardiac damage for risk stratification in patients undergoing transcatheter aortic valve replacement (TAVR) in a real-world cohort and to examine the addition of baseline albumin in risk assessment. METHODS AND RESULTS: We investigated 2608 patients undergoing TAVR. Subjects were divided into five groups based on their echocardiography findings. Patients were further assessed by incorporating baseline albumin. Multivariable analysis demonstrated that each increase in stage was associated with significant increased risk of 1-year mortality (HR 1.37, 95%CI 1.23-1.54, p < .001). Among patients at increased stage (3-4), incorporation of baseline of albumin identified the highest risk group, such that each 1 decrement in albumin levels was associated with more than triple increase in mortality among patients at stage 3 and 4 (HR 2.77, 95% CI 1.48-5.18, p-value = .001). CONCLUSIONS: Cardiac damage classification is validated in a real-world cohort of patients undergoing TAVR. Incorporation of low baseline albumin may further identify patients at the highest risk group. CONDENSTED ABSTRACT: We evaluated 2608 patients undergoing transcatheter aortic valve replacement (TAVR) in order to validate a new scoring system dividing patients in to 5 stages (0-4) based on extent of cardiac damage. Patients were further assessed by incorporating baseline albumin. Multivariable analysis demonstrated that each increase in stage was associated with significant increased risk of 1-year mortality. Furthermore, among patients at increased stage (3-4), incorporation of baseline of albumin identified the highest risk group, such that each 1 decrement in albumin levels was associated with more than triple increase in mortality among patients at stage 3 and 4.

Effect of Statin Therapy and Long-Term Mortality Following Transcatheter Aortic Valve Implantation.

Increased inflammatory response after aortic valve replacement is linked to higher postprocedural mortality. The aim of the present analysis was to assess the impact of baseline statin therapy on procedural outcomes and mortality after transcatheter aortic valve implantation (TAVI). We performed a retrospective analysis on patients who underwent TAVI stratified to 3 statin therapy groups: high-intensity statin (HIS), low-medium intensity statins, and no statin. Included were 1,238 patients. Patients treated with HIS were significantly younger, had higher body mass index, lower Society of Thoracic Surgeons score, and higher prevalence of dyslipidemia, hypertension, past stroke, and ischemic heart disease. Procedural outcomes were similar between groups. There were no statistically significant short-term mortality differences at 1 month (2.2% vs 2.1% vs 3.5%, p = 0.50) and 1 year (6.9% vs 9.3% vs 14.2%, p = 0.15), albeit the observed numerical trend. As for long-term mortality (median follow time of 2.5 years, interquartile range 1.3 to 4.2), lower mortality rates were observed in the HIS group (14.5% vs 25.2% vs 36.6%, p = 0.001). Compared with no statin, the HIS group was significantly associated with reduced risk of long-term mortality in multivariate analysis (hazard ratio = 0.59, 95% CI 0.37 to 0.96, p = 0.03). Baseline HIS therapy is associated with reduced rates of long-term morality after TAVI.

ß-Cell DNA Damage Response Promotes Islet Inflammation in Type 1 Diabetes.

Type 1 diabetes (T1D) is an autoimmune disease where pancreatic ß-cells are destroyed by islet-infiltrating T cells. Although a role for ß-cell defects has been suspected, ß-cell abnormalities are difficult to demonstrate. We show a ß-cell DNA damage response (DDR), presented by activation of the 53BP1 protein and accumulation of p53, in biopsy and autopsy material from patients with recently diagnosed T1D as well as a rat model of human T1D. The ß-cell DDR is more frequent in islets infiltrated by CD45+ immune cells, suggesting a link to islet inflammation. The ß-cell toxin streptozotocin (STZ) elicits DDR in islets, both in vivo and ex vivo, and causes elevation of the proinflammatory molecules IL-1ß and Cxcl10. ß-Cell-specific inactivation of the master DNA repair gene ataxia telangiectasia mutated (ATM) in STZ-treated mice decreases the expression of proinflammatory cytokines in islets and attenuates the development of hyperglycemia. Together, these data suggest that ß-cell DDR is an early event in T1D, possibly contributing to autoimmunity.