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Abstract Background and Aims Presentation, outcome, and management of females with degenerative mitral regurgitation (DMR) are undefined. We analysed sex-specific baseline clinical and echocardiographic characteristics at referral for DMR due to flail leaflets and subsequent management and outcomes. Methods In the Mitral Regurgitation International Database (MIDA) international registry, females were compared with males regarding presentation at referral, management, and outcome (survival/heart failure), under medical treatment, post-operatively, and encompassing all follow-up. Results At referral, females (n = 650) vs. males (n = 1660) were older with more severe symptoms and higher MIDA score. Smaller cavity diameters belied higher cardiac dimension indexed to body surface area. Under conservative management, excess mortality vs. expected was observed in males [standardized mortality ratio (SMR) 1.45 (1.27–1.65), P < .001] but was higher in females [SMR 2.00 (1.67–2.38), P < .001]. Female sex was independently associated with mortality [adjusted hazard ratio (HR) 1.29 (1.04–1.61), P = .02], cardiovascular mortality [adjusted HR 1.58 (1.14–2.18), P = .007], and heart failure [adjusted HR 1.36 (1.02–1.81), P = .04] under medical management. Females vs. males were less offered surgical correction (72% vs. 80%, P < .001); however, surgical outcome, adjusted for more severe presentation in females, was similar (P ≥ .09). Ultimately, overall outcome throughout follow-up was worse in females who displayed persistent excess mortality vs. expected [SMR 1.31 (1.16–1.47), P < .001], whereas males enjoyed normal life expectancy restoration [SMR 0.92 (0.85–0.99), P = .036]. Conclusions Females with severe DMR were referred to tertiary centers at a more advanced stage, incurred higher mortality and morbidity under conservative management, and were offered surgery less and later after referral. Ultimately, these sex-related differences yielded persistent excess mortality despite surgery in females with DMR, while males enjoyed restoration of life expectancy, warranting imperative re-evaluation of sex-specific DMR management.

Introduction: The survival impact of impaired multi-chamber longitudinal strain in significant tricuspid aortic valve stenosis(TAV-AS) and its relation to cardiac damage staging(CDS) is unknown. Hypothesis: Impaired strain improves prognostication of CDS in significant TAV-AS. Methods: We performed 2D-semi-automated strain analysis in a retrospective cohort of consecutive patients with TAV-AS with mean pressure gradient≥30mmHg on echocardiogram. The outcome was all-cause death. Cutoffs of impaired left-ventricular global longitudinal strain(

Introduction: Atrial fibrillation (AF) is a serious complication, which occurs in 30% to 40% of patients after surgical aortic valve replacement (SAVR) and contributes to adverse outcomes. Advanced technology has enabled transcatheter aortic valve replacement (TAVR) in patients with High-risk Severe Aortic Stenosis (HRSAS). In these patients, the compliance of the systemic vasculature is an independent predictor of diastolic dysfunction, a known predictor of postoperative AF (POAF). We hypothesize that patients with HRSAS undergoing TAVR represent a population at increased risk for POAF. METHODS: The medical records of 195 TAVR patients at the Mayo Clinic from November 2008 to January 2013 were analyzed. All patient demographic, clinical, pre- and post-procedural outcomes were collected from the patients’ medical records, and reviewed to ascertain all cases of POAF (AF ≤30 days of surgery). Patients with a prior history of AF (n= 75 (38.5%)) were excluded. Logistic regression analysis was used to identify clinical predictors of POAF after TAVR. Results: The mean age of the study population was 80.8±7.8 years and 60.8% (n=73) were men. The mean STS risk score was 8.9±5.1. Of the 120 patients without prior AF, 20.8% (n=25) developed new-onset POAF after TAVR. Patients who developed POAF were more likely to have undergone a transapical or transaortic TAVR approach (OR 3.20; 95% CI (1.3-8.0), had a higher incidence of renal complications (52.0% vs 21.5%; p= 0.003), greater hospital length of stay (7.4±2.58 vs 5.0±2.6 days; p= 0.0003, and a trend toward higher 30-day mortality (28.0% vs 13.7%; p= 0.09) and pulmonary complications (16.0% vs 5.4%; p= 0.08) compared with those who did not develop POAF, respectively. Neurologic complications were not different between the 2 group (4.0% vs 3.2%; p= 0.85). Conclusions: Patients with High-risk Severe Aortic Stenosis undergoing TAVR have increased risk of POAF, primarily associated with a transapical or aortic surgical approach. Patients who develop POAF had higher incidence of post-procedural complications and longer hospitalizations. Therefore, perioperative strategies aimed at prevention of POAF are as important in TAVR patients as in those undergoing SAVR.

Background: Left ventricular (LV) mass regression after aortic valve replacement (AVR) for aortic stenosis (AS) is a favorable effect of LV unloading, but its relationship to improved clinical outcomes is unclear. We examined the effect on clinical outcomes after transcatheter AVR (TAVR) of: 1) amount of LV mass index (LVMi) regression; and 2) persistent severe LV hypertrophy (LVH). Methods: Of 2115 patients with symptomatic AS at high surgical risk receiving TAVR in the PARTNER randomized trial or continued access registry, 462 (55% women) who had severe LVH (LVMi ≥149 g/m 2 men, ≥122 g/m 2 women, by ASE criteria) at baseline (BL) and LVMi measured 6 mo post-TAVR were included in our analysis. The effect of LVMi regression was evaluated by comparing outcomes in patients with greater vs. lesser decrease (dichotomized by median % change) in LVMi between BL and 6 mo, and in those without vs. with persistent severe LVH 6 mo post-TAVR. Cox PH models evaluated rates of all-cause mortality (6-12 mo), rehospitalizations (through 1 yr), and the composite of these two outcomes. Results: LVMi decreased from 173±32 (BL) to 121±25 g/m 2 (6 mo) (p<0.001) in those with greater LVMi regression, and from 164±30 (BL) to 158±34 g/m 2 (6 mo) (p<0.001) in those with lesser LVMi regression. Patients with greater vs. lesser LVMi regression had similar baseline clinical characteristics, a lower rate of rehospitalization (10.5% vs. 19.9%, p=0.006) and lower rate of the composite endpoint of death or rehospitalization (13.2% vs. 21.4%, p=0.02), but a similar rate of death (4.9% vs. 4.8%, p=0.86). Persistent severe LVH at 6 mo post-TAVR was present in 54% (58% of whom were women). Patients without vs. with persistent severe LVH had similar baseline clinical characteristics, a lower rate of rehospitalization (11.9% vs. 18.1%, p=0.053) and lower rate of the composite endpoint of death or rehospitalization (13.3% vs. 20.7%, p=0.03), but a similar rate of death (3.9% vs. 5.7%, p=0.42). Similar results were obtained when including patients with moderate or severe LVH. Conclusions: In high-risk patients with severe AS and severe LVH undergoing TAVR, greater LV mass regression and resolution of initially severe LVH at 6 months are associated with a lower rate of death or repeat hospitalization.

Background: Aortic Valve Calcification (AVC) is intrinsic to aortic stenosis (AS). While established concepts assume homogeneous calcification causing AS, wide variability in hemodynamic severity at any given AVC burden suggests other operative mechanisms. Multidetector computed tomography (MDCT) now accurately measures global AVC, but AVC spatial distribution remains elusive due to imaging orientation. Methods and Results: We developed ‘en-face’ imaging by re-registration of 4D-MDCT to quantify AVC spatial distribution and analyzed global AVC load and AVC distribution in 418 patients with AS (76±9 years; mean gradient 35±17 mmHg). 4D-volume-rendered MDCT datasets were re-oriented to en-face view of aortic valve for AVC spatial scoring with individual cusp calcification load, cusp-edge calcification and AVC asymmetry. Despite high total AVC load (450 [250-666] AU/cm 2 ), asymmetry was frequent (50%), with a difference between most- and least-calcified cusp of 112 [66-182] AU/cm 2 . Maximum AVC was in the non-coronary cusp in 61% (p<0.001). Cusp edge calcification was none-mild in 26%, moderate in 62% and severe in 12%. Adjusting for total AVC, severe AS (mean gradient >40 mmHg) was more likely with symmetrical AVC (odds ratio [OR] 2.36, p<0.001) and with edge calcification moderate (OR 4.16, p=0.001 vs none-mild) to severe (OR 10.7, p=0.001). Inclusion of AVC distribution improved models predicting AS severity over total AVC (p<0.001). Conclusions: Four-dimensional MDCT en-face re-registration and AVC quantitation provides new insight into AS pathophysiology. Contrary to classical concepts, AVC is frequently inhomogeneous and asymmetric. Hemodynamic AS severity is independently affected not only by global AVC but also by variations in AVC distribution and location within cusps, emphasizing the importance of 4D AVC assessment in AS. Impact of quantified AVC asymmetry and location on outcome of transcutaneous aortic valve replacement should be evaluated.

Introduction: Soluble ST2 (sST2) is a serum marker of cardiomyocyte stress associated with a large risk of death and heart failure after myocardial infarction (MI). The relationship between sST2 and cardiac structure and function after MI however remains incompletely defined, and greater characterization is required prior to clinical application. Methods: Olmsted County, Minnesota residents who experienced their first MI between 2007 and 2012 were prospectively recruited. MIs were validated using standardized criteria and patients underwent simultaneous comprehensive Doppler echocardiography and sST2 measurement. The association between cardiac morphology and hemodynamics and sST2 were examined. Published normal values were used as referent ranges for sST2 levels. Results: Among 316 patients (mean age 65 [SD 14] years, 67% men, 32% ST-elevation MI), sST2 was measured 2.5 [SD 1.6] days after MI and within 0.7 [SD 2.3] days of echocardiography. Soluble ST2 was elevated in 33% of patients and univariately associated with decreased LV ejection fraction (LVEF), increased LV mass, impaired LV diastolic function and increased pulmonary artery pressure (ePAP) (Table). After adjustment for age, sex, LVEF and key measures of LV filling pressures, elevated sST2 was independently associated with reduced LVEF (p=0.01) mitral valve deceleration time (p=0.03), greater left atrial volume (p=0.03) and mitral regurgitation (≥mild; p=0.09). LVEF and ePAP exhibited the strongest associations with elevated sST2 (both p<0.001). Conclusions: Soluble ST2 is frequently elevated following MI and is strongly associated with the morphologic and hemodynamic determinants of adverse LV remodeling that infer poor long-term outcome after MI.

Introduction: Aortic Stenosis (AS) is a common valve disease of the adult, caused by calcification of aortic cusps. The relationship between cusp calcification and severity of AS has been established mostly in men and it is unclear whether the calcification process and its relation to AS severity is similar in women Hypothesis: We hypothesized that the physiologic relation between aortic valve calcification (AVC) load and AS severity is different in men and women and that lower calcification loads may lead to severe AS in women Methods: We prospectively performed high resolution computed tomography (CT) without contrast in 679 patients with AS (Aortic valve area (AVA) <2cm 2 , Mean gradient ≥10 mmHg) at two academic centers (Rochester, MN; Paris, France) to measure AVC scores and compare these to the hemodynamic obstruction measured by Echo-Doppler. Results: Women vs. men were older (76±11 vs 74±11, p<0.0001) with slightly higher ejection fraction (62±12 vs 59±13, p=0.001) but AS severity was similar (AVA/body surface area 0.55±0.2 vs 0.56±0.2 cm 2 /m 2 ; Peak velocity 4±1 vs 3.9±1 m/s; Mean gradient 41±21 vs 38±18 mmHg, all p≥0.1). Yet, AVC load was lower in women vs men, score absolute or normalized for LVOT area (551±383 vs 626±399 all p<0.0001). For those with severe AS (Mean gradient >40 mmHg), AVC scores were 2433±1412 in women vs 3805±1587 in men. Multivariate analysis adjusting for age, BSA, LVOT area and mean gradient, confirmed that severe AS was achieved with lower AVC load in women (all p<0.0001). Conclusions: In this large multicenter AS population, women reached similar AS severity than males for lower calcium loads, even after adjustment for lower body and LVOT size. Hence the relation between valvular calcification process and severity of AS differs in women vs. men. Thus, future studies are needed to determine the differential mechanism of aortic calcification in men and women and diagnostic consideration must be given to gender in the interpretation of AS severity by AVC load.

Objective To test the hypothesis that the numbers of circulating endothelial progenitor cells (EPC) co-expressing an osteogenic phenotype (EPC-OC) are increased in patients with clinically severe calcific aortic valve stenosis (AoC). Background AoC is one of the most common valvular heart diseases. Recent studies have shifted the old paradigm of AoC being a passive, degenerative process to an active biological process associated with an osteoblast-like phenotype. We have recently identified circulating EPC-OC which are significantly increased in patients with severe coronary artery disease (CAD). Methods and Results Of 38 patients, 14 underwent aortic valve replacement due to AoC with only mild angiographic CAD. Patients with normal aortic valves and coronary arteries (n=12) or severe CAD without aortic valve disease (n=12) served as controls (Table ). Peripheral blood mononuclear cells were analyzed using flow cytometry following staining for EPC markers (CD133, CD34, KDR) and the osteoblastic marker, osteocalcin (OC). Patients with AoC had significantly higher fractions of OC co-expression on EPC of different maturity than normal patients, similar to patients with CAD (Figure ). Conclusions Circulating EPC co-expressing an osteoblastic phenotype are increased and may potentially play a role in the active process of aortic valve calcification. Table. Clinical Data.

Abstract Background and Aims Severe aortic stenosis (AS) is the guideline-based indication for aortic valve replacement (AVR), which has markedly increased with transcatheter approaches, suggesting possible increasing AS incidence. However, reported secular trends of AS incidence remain contradictory and lack quantitative Doppler echocardiographic ascertainment. Methods All adults residents in Olmsted County (MN, USA) diagnosed over 20 years (1997–2016) with incident severe AS (first diagnosis) based on quantitatively defined measures (aortic valve area ≤ 1 cm2, aortic valve area index ≤ 0.6 cm2/m2, mean gradient ≥ 40 mmHg, peak velocity ≥ 4 m/s, Doppler velocity index ≤ 0.25) were counted to define trends in incidence, presentation, treatment, and outcome. Results Incident severe AS was diagnosed in 1069 community residents. The incidence rate was 52.5 [49.4–55.8] per 100 000 patient-year, slightly higher in males vs. females and was almost unchanged after age and sex adjustment for the US population 53.8 [50.6–57.0] per 100 000 residents/year. Over 20 years, severe AS incidence remained stable (P = .2) but absolute burden of incident cases markedly increased (P = .0004) due to population growth. Incidence trend differed by sex, stable in men (incidence rate ratio 0.99, P = .7) but declining in women (incidence rate ratio 0.93, P = .02). Over the study, AS clinical characteristics remained remarkably stable and AVR performance grew and was more prompt (from 1.3 [0.1–3.3] years in 1997–2000 to 0.5 [0.2–2.1] years in 2013–16, P = .001) but undertreatment remained prominent (&gt;40%). Early AVR was associated with survival benefit (adjusted hazard ratio 0.55 [0.42–0.71], P &lt; .0001). Despite these improvements, overall mortality (3-month 8% and 3-year 36%), was swift, considerable and unabated (all P ≥ .4) throughout the study. Conclusions Over 20 years, the population incidence of severe AS remained stable with increased absolute case burden related to population growth. Despite stable severe AS presentation, AVR performance grew notably, but while declining, undertreatment remained substantial and disease lethality did not yet decline. These population-based findings have important implications for improving AS management pathways.

Introduction: Criteria for aortic valve intervention (AVI) in severe aortic stenosis (AS) rely on symptoms, left ventricular ejection fraction (LVEF) and AS severity. Computed tomography-based aortic valve calcification (CT-AVC) scores associated with severe AS also have prognostic value, but this remains unexplored in patients with non-severe AS. We aimed to assess the prognostic value of AVC in asymptomatic patients with nonsevere AS and preserved LVEF. Methods: We retrospectively identified 395 patients with ≥mild AS but less-than-severe AS by echocardiography, who had CT-AVC assessed within six months. AVCscore was quantified offline by Agatston method (TeraRecon software), and also indexed by LV outflow track area, i.e., AVCdensity. Patients were followed until AVI or death. The primary outcome was all-cause death under medical surveillance. Results: In 395 patients, mean age was 73±12 years, 61% were men, mean aortic valve area 1.2±0.3cm2, mean gradient 28±9 mmHg, peak velocity 3.4±0.5 m/s, LVEF 64±6%. During a follow-up of 2.2[0.74-4.94] years, 220 patients had AVI and 82 patients died. Both AVCscore and AVCdensity were associated with AVI-free survival and the best AVCscore thresholds associated with mortality were 853 in women and 1183 in men by log-rank test (both p<0.001). High AVCscore and high AVCdensity were associated with increased hazard for all-cause death in unadjusted and adjusted analyses (Figure), and after further adjustment for echocardiographic severity (all p ≤0.01). Conclusions: In asymptomatic patients with less-than-severe AS, sex-specific CT-AVC scores differentiate those at higher risk for death versus lower risk. Whether AVI could modify this risk remains to be proven.