Impact of Baseline Left Ventricular Diastolic Dysfunction in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation.

We sought to assess the impact of diastolic dysfunction (DD) grade, as per the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines, on survival of patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve implantation (TAVI). We included consecutive patients with severe AS who underwent TAVI in our institution. DD grading was determined retrospectively according to the 2016 ASE DD guidelines and categorized to grade I-III and indeterminate grade I-II DD. Comparison of 1-year survival according to DD grade was performed by Kaplan-Meier analysis, and evaluation of DD at 1 year was performed in a subset of patients. Among 606 TAVI patients, 394 (65%) had sufficient data for DD grading. Seventy-seven (20%) had grade I DD, 191 (48%) had grade II, 60 (15%) had grade III, and 66 (17%) had an indeterminate grade between I and II. Baseline characteristics indicate higher rates of atrial fibrillation, brain natriuretic peptide level, pulmonary artery systolic pressure, and indexed left ventricular mass as DD grade increases (all p ≤0.01). In conclusion, comparison of 1-year survival revealed a higher rate of mortality in patients with grade III DD that remained statistically significant following adjustment in a multivariate Cox proportional hazard model. DD grade after TAVI improved in patients with grades II and III. Severe AS patients with grade III DD have higher risk for 1-year mortality after TAVI compared with milder degrees of DD. Further research is warranted to explore a potential benefit for aortic valve therapy at an earlier stage of the disease process.

Role of contractile reserve as a predictor of mortality in low-flow, low-gradient severe aortic stenosis following transcatheter aortic valve replacement.

OBJECTIVES: The aim of this study was to determine the prognostic value of contractile reserve (CR) at baseline in patients with low-flow, low-gradient severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Patients with severe AS, left ventricular dysfunction, and low transaortic gradient are at high risk for mortality during surgical aortic valve replacement (SAVR). Furthermore, patients without CR have been shown to have perioperative mortality comparable to that of patients treated medically for severe AS. METHODS: We retrospectively analyzed patients who underwent TAVR with a diagnosis of low-gradient severe AS (mean transvalvular aortic gradient < 40 mmHg, LVEF < 50%, and AVA ≤ 1.0 cm2 or AVAi ≤ 0.6 cm2 ) and who had a pre-TAVR dobutamine stress echocardiogram (DSE). Patients were stratified by the presence or absence of CR, defined as an increase in stroke volume ≥ 20% during DSE. RESULTS: From 2008 to 2016, 61 patients with low-gradient severe AS underwent TAVR and had pre-TAVR DSE. CR was present in 31 patients (51%) and absent in 30 (49%). There was no significant difference between the two groups in baseline demographics, medical history, access site, or types of valves. All-cause mortality was similar in both groups at 30 days (13% with CR vs 10% without CR, P = 1.00) and 1 year (29% with CR vs 33% without CR, HR 1.20, 95% CI 0.49-2.96, P = 0.69). CONCLUSION: In patients with low-flow, low-gradient severe AS undergoing TAVR, the presence or absence of CR does not predict all-cause mortality at 30 days or 1 year.

Utility of an additive frailty tests index score for mortality risk assessment following transcatheter aortic valve replacement.

BACKGROUND: The impact of frailty assessment on outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) remains unclear. Our aim was to evaluate the individual effect of each frailty test and the utility of an additive frailty index score on short- and long-term survival following TAVR. METHODS: Retrospective analysis of consecutive TAVR patients for whom a complete set of frailty tests was obtained: algorithm defined grip strength and 5-m walking tests, body mass index <20 kg/m2, Katz activities of daily living ≤4/6, serum albumin <3.5 g/dL. Frailty status was defined as having 3 or more positive frailty tests. Included were 498 patients with a mean age of 82±8 years. RESULTS: Frailty status, observed in 266 (53%) patients, was associated with both 30-day and 1-year mortality (6% vs. 2%, P=.016; 20% vs. 9%, P<.001; within the respective frailty groups). As compared to 0-2 frailty criteria, a higher frailty index score was associated with increased risk of death at 1 year (OR 2.23; 95% CI 1.14-4.34; P=.019 and OR 3.30; 95% CI 1.36-8.00; P=.008 for 3 and 4-5 frailty criteria met, respectively). In Cox regression analysis, frailty status was correlated with 1-year mortality (HR=2.2; 95%CI 1.25-3.96; P=.007), and a higher frailty index was associated with increased mortality risk (HR=2.0; 95% CI 1.08-3.7; P=.027; and HR=3.07; 95% CI 1.4-6.7; P=.005; for any 3, and 4-5 frailty criteria, respectively). CONCLUSIONS: Frailty status and a higher frailty index score were associated with increased 1-year mortality risk following TAVR.

In-Stent Restenosis of Drug-Eluting Stents Compared With a Matched Group of Patients With De Novo Coronary Artery Stenosis.

Drug-eluting stents (DES) significantly reduced the incidence of in-stent restenosis (ISR). However, ISR still exists in the contemporary DES era. Previously deemed to be a benign process, ISR leads to complex presentation and intervention. This study aimed to compare the presentation and outcome of DES-ISR versus de novo lesions. We performed a retrospective analysis of 11,666 patients receiving percutaneous coronary intervention from 2003 to 2017 and divided them into 2 groups by de novo stenosis and ISR. They were matched based on common cardiovascular risk factors at a 4:1 ratio, respectively. After matching, a total of 1,888 patients with 3,126 de novo lesions and 472 patients with 508 ISR lesions were analyzed. Patients with ISR presented more often with unstable angina (61% vs 45%, p <0.001) and less often with myocardial infarction (6% vs 14%, p <0.001). One-year composite major adverse cardiovascular event, defined as death, Q-wave myocardial infarction, and target vessel revascularization, was 10% in the de novo group and 17% in the ISR group (hazard ratio 1.98, 95% confidential interval 1.58 to 2.46, p <0.001). After adjusting for myocardial infarction presentation, hazard ratio of major adverse cardiovascular events was still higher for the ISR group at 1 year (2.03, 95% confidential interval 1.62 to 2.55, p <0.001). ISR of DES remains a therapeutic challenge and leads to complex presentation and worse outcomes compared with matched de novo patients. These data show that DES-ISR demands better appreciation and prevention with more precise stent technique and should motivate the continued development of fully bioresorbable scaffolds.

Temporal trends in patient referral for Transcatheter aortic valve replacement and reasons for exclusion at a high-volume Center in the United States.

BACKGROUND: Clinical indications for transcatheter aortic valve replacement (TAVR) and elements of the implantation procedure, including delivery system miniaturization and novel access options, have evolved over time. The reasons patients are excluded from TAVR also have changed. The impact of these changes on patient referral for and exclusion from TAVR is unknown. METHODS: We retrospectively analyzed patients referred to our center for TAVR from January 2010 to August 2016 to evaluate reasons for patient exclusion. Patients were divided into three groups based on initial screening date for trends in demographics and exclusion: Group 1, 2010-2012; Group 2, 2012-2014; Group 3, 2014 to August 1, 2016. Annual trends for patient exclusion from TAVR were assessed. RESULTS: One thousand nine hundred fifty-three patients were referred and underwent screening for TAVR. The rates at which patients were referred for TAVR were 23.8, 25.9, and 24.5 per month in groups 1, 2, and 3, respectively. Rate of patient exclusion from TAVR decreased from 68% in Group 1 to 38% in Group 3 (P < .001). The largest percentage of patients (29.4%) were initially excluded from TAVR for cardiac reasons, but this trend has decreased over time. Twenty-five percent are excluded for lack of procedural indication. Exclusion from TAVR for vascular access reasons decreased from 7.9% in 2010 to 1.0% in 2016 (P = .017). CONCLUSIONS: Referral numbers have been robust since TAVR became available. The percentage of patients excluded from TAVR has decreased over time. Patients are most commonly excluded from TAVR for concomitant coronary artery disease (CAD), asymptomatic severe AS, moderate AS, or non-cardiac critical illness. Patients with CAD and those with asymptomatic severe AS or moderate AS should be a focus for continued research in TAVR.

Reproductive and menstrual factors and colorectal cancer incidence in the Women's Health Initiative Observational Study.

BACKGROUND: Reproductive and menstrual factors have been evaluated as surrogates for long-term hormonal exposures in several prospective studies of colorectal cancer, yet findings have been conflicting. METHODS: The relation of reproductive and menstrual factors (self-reported via a reproductive history questionnaire) with incident colorectal cancer was investigated among women enrolled in the Women's Health Initiative Observational Study (WHI-OS), a longitudinal cohort of 93 676 postmenopausal women (aged 50-79 years at enrolment) in which 1149 incident cases of colorectal cancer occurred over a median follow-up of 11.9 years. Multivariable Cox proportional hazards models that included established colorectal cancer risk factors were constructed to examine the association of colorectal cancer incidence with reproductive and menstrual factors. RESULTS: Having had two children (vs nulliparous: hazard ratio (HR)=0.80, 95% confidence interval (CI): 0.64-0.99) was inversely associated with colorectal cancer risk. Compared with never users, ever use of oral contraceptives was associated with lower colorectal cancer risk (HR=0.74, 95% CI: 0.63-0.86); however, no relationship was observed for duration of oral contraceptives use (4 years vs 1 year: HR=0.94, 95% CI: 0.67-1.32). None of the remaining reproductive and menstrual factors was associated with colorectal cancer incidence. CONCLUSIONS: Parity and prior use of oral contraceptives were associated with lower colorectal cancer risk in this cohort of postmenopausal women.

The adipokine profile of metabolically benign obese and at-risk normal weight postmenopausal women: the Women's Health Initiative Observational Study.

OBJECTIVE: Nearly, a third of obese individuals, termed metabolically benign obese, have a low burden of adiposity-related cardiometabolic abnormalities, whereas a substantial proportion of normal-weight individuals possess risk factors. METHODS: In cross-sectional analyses of 699 normal weight and 1,294 overweight/obese postmenopausal women enrolled in a nested case-control stroke study ancillary to the Women's Health Initiative Observational Study, we compared levels of adiponectin, leptin, and resistin among metabolically benign normal weight, at-risk normal weight, metabolically benign obese, and at-risk obese women using components of the ATP III definition of the metabolic syndrome (metabolically benign: ≤1 of the four components; at-risk phenotype: ≥2 components or diabetes). RESULTS: Overall, 382/699 normal-weight women (54.6%) and 328/1,194 overweight/obese women (27.5%) were metabolically benign. Among normal-weight women, at-risk women had higher leptin and lower adiponectin levels compared to metabolically benign women; multivariate-adjusted odds ratios were significant for having leptin (OR: 2.51; 95% CI: 1.28-5.01) and resistin (1.46; 1.03-2.07) in the top tertile and adiponectin in the bottom tertile (2.64; 1.81-3.84). Compared to metabolically benign overweight/obese women, at-risk obese women had higher odds of having leptin in the top tertile (1.62; 1.24-2.12) and adiponectin in the bottom tertile (2.78; 2.04-3.77). CONCLUSIONS: Overall, metabolically benign overweight/obese women had an intermediate adipokine profile (between at-risk obese and metabolically benign normal-weight women), whereas at-risk normal-weight women had a less favorable profile compared to metabolically benign normal-weight women. As adiponectin was the only adipokine independent of BMI, it may be most likely to have a role in the etiological pathway of these phenotypes.

Serosurvey for antibody to deerpox virus in five cervid species in Oregon, USA.

Five cervid species in Oregon, USA were tested with a serum neutralization assay for antibody to deerpox virus (DPV). None of the 50 elk (Cervus elaphus ssp. roosevelti and nelsonii) had detectable antibody. Prevalence of antibody to DPV in the remaining species was: 52% (n=55) in black-tailed deer (Odocoileus hemionus columbianus), 32% (n= 59) in mule deer (O. hemionus hemionus), and 36% (n=50) in Columbian white-tailed deer (O. virginianus leucurus), with an overall antibody prevalence of 40.2% (n=164) for Odocoileus spp. Antibody-positive animals were identified throughout the state with no statistically significant differences among geographic regions. No statistically significant gender or age-related differences in antibody prevalence were demonstrated at either the genus or species level. This serosurvey indicates that exposure to DPV is common in Odocoileus populations in Oregon. Given the low rates of observed DPV-related disease, this high antibody prevalence suggests a pathogen of low virulence.

Perception of weight status and its impact on gestational weight gain in an urban population.

To examine the association between actual and perceived overweight/obese status and excess gestational weight gain (GWG). As part of an infant feeding trial, multi-ethnic lower and moderate income women-completed a checklist of current health conditions, including "overweight/obesity," "asthma," and "hypertension" while pregnant. Odds of excessive GWG per the Institute of Medicine guidelines in 'accurate' versus 'inaccurate' reporters, by overweight status were analyzed with multivariate logistic regression for women with pre-or early pregnancy BMIs of ≥18.5. 775 women met study criteria. Just 21 % (n = 107) of overweight/obese women accurately identified their weight status, compared to >90 % accurate report of documented hypertension or asthma. Compared to normal-weight accurate reporters, the adjusted odds of excessive GWG in overweight/obese women was 2.3 (95 % CI 1.4, 3.7) in accurate reporters, and 2.5 (95 % CI 1.7, 3.4) in inaccurate reporters. Overweight/obesity is associated with excessive GWG, but this risk is not modified by inaccurate reporting/perception of weight-status.

Pediatric sleep disorders and special educational need at 8 years: a population-based cohort study.

OBJECTIVES: To examine associations between sleep-disordered breathing (SDB) and behavioral sleep problems (BSPs) through 5 years of age and special educational need (SEN) at 8 years. METHODS: Parents in the Avon Longitudinal Study of Parents and Children reported on children's snoring, witnessed apnea, and mouth-breathing at 6, 18, 30, 42, and 57 months, from which SDB symptom trajectories, or clusters, were derived. BSPs were based on report of ≥ 5 of 7 sleep behaviors at each of the 18-, 30-, 42-, and 57-month questionnaires. Parent report of SEN (yes/no) at 8 years was available for 11049 children with SDB data and 11467 children with BSP data. Multivariable logistic regression models were used to predict SEN outcome by SDB cluster and by cumulative report of SEN. RESULTS: Controlling for 16 putative confounders, previous history of SDB and BSPs was significantly associated with an SEN. BSPs were associated with a 7% increased odds of SEN (95% confidence interval [CI] 1.01-1.15), for each ∼1-year interval at which a BSP was reported. SDB, overall, was associated with a near 40% increased odds of SEN (95% CI 1.18-1.62). Children in the worst symptom cluster were 60% more likely to have an SEN (95% CI 1.23-2.08). CONCLUSIONS: In this population-based longitudinal study, history of either SDB or BSPs in the first 5 years of life was associated with increased likelihood of SEN at 8 years of age. Findings highlight the need for pediatric sleep disorder screening by early interventionists, early childhood educators, and health professionals.

Sleep-disordered breathing in a population-based cohort: behavioral outcomes at 4 and 7 years.

OBJECTIVES: Examine statistical effects of sleep-disordered breathing (SDB) symptom trajectories from 6 months to 7 years on subsequent behavior. METHODS: Parents in the Avon Longitudinal Study of Parents and Children reported on children's snoring, mouth breathing, and witnessed apnea at ≥2 surveys at 6, 18, 30, 42, 57, and 69 months, and completed the Strengths and Difficulties Questionnaire at 4 (n = 9140) and 7 (n = 8098) years. Cluster analysis produced 5 "Early" (6-42 months) and "Later" (6-69 months) symptom trajectories ("clusters"). Adverse behavioral outcomes were defined by top 10th percentiles on Strengths and Difficulties Questionnaire total and subscales, at 4 and 7 years, in multivariable logistic regression models. RESULTS: The SDB clusters predicted ≈20% to 100% increased odds of problematic behavior, controlling for 15 potential confounders. Early trajectories predicted problematic behavior at 7 years equally well as at 4 years. In Later trajectories, the "Worst Case" cluster, with peak symptoms at 30 months that abated thereafter, nonetheless at 7 years predicted hyperactivity (1.85 [1.30-2.63]), and conduct (1.60 [1.18-2.16]) and peer difficulties (1.37 [1.04-1.80]), whereas a "Later Symptom" cluster predicted emotional difficulties (1.65 [1.21-2.07]) and hyperactivity (1.88 [1.42-2.49]) . The 2 clusters with peak symptoms before 18 months that resolve thereafter still predicted 40% to 50% increased odds of behavior problems at 7 years. CONCLUSIONS: In this large, population-based, longitudinal study, early-life SDB symptoms had strong, persistent statistical effects on subsequent behavior in childhood. Findings suggest that SDB symptoms may require attention as early as the first year of life.

Prevalence and persistence of sleep disordered breathing symptoms in young children: a 6-year population-based cohort study.

STUDY OBJECTIVES: To describe the prevalence, persistence, and characteristics associated with sleep disordered breathing (SDB) symptoms in a population-based cohort followed from 6 months to 6.75 years. DESIGN: Avon Longitudinal Study of Parents and Children (ALSPAC). SETTING: England, 1991-1999. PARTICIPANTS: 12,447 children in ALSPAC with parental report of apnea, snoring, or mouth-breathing frequency on any one of 7 questionnaires. MEASUREMENTS: Symptom prevalence rates-assessed as "Always" and "Habitually"-are reported at 0.5, 1.5, 2.5, 3.5, 4.75, 5.75, and 6.75 years of age. The proportion of children in whom symptoms develop, persist or abate between observation points is reported. Exploratory multivariate analyses identified SDB risk factors at 1.5, 4.75, and 6.75 years. RESULTS: The prevalence of apnea ("Always") is 1%-2% at all ages assessed. In contrast, snoring "Always" ranges from 3.6% to 7.7%, and snoring "Habitually" ranges from 9.6% to 21.2%, with a notable increase from 1.5- 2.5 years. At 6 years old, 25% are habitual mouth-breathers. The "Always" and "Habitual" incidence of each symptom between time points is 1%-5% and 5%-10%, respectively. In multivariate analyses of combined symptoms, socioeconomic factors have stronger, more persistent effects upon increased SDB risk than gestational age, gender, or race (aside from 1.5 years); adenoidectomy decreases risk by 40%-50%. CONCLUSIONS: This is the first natural history study of the primary symptoms of SDB across a key 6-year period in the development of SDB symptoms. Snoring rates are higher and spike earlier than previously reported. Symptoms are dynamic, suggesting the need for early and continued vigilance in early childhood.