Sex-related differences in the trends and outcomes of trans-septal transcatheter mitral valve replacement: Insights from the National Readmissions Database.

BACKGROUND: There is a paucity of data regarding the sex-related differences in the trends and outcomes of trans-septal transcatheter mitral valve replacement (TS-TMVR). METHODS: The Nationwide Readmissions Database (2015-2018) was queried for admissions for TS-TMVR. Propensity matched analysis was conducted to compare outcomes with hospitalizations for TS-TMVR among women versus men. The main study outcome was in-hospital mortality. RESULTS: Our final analysis included 2063 hospitalizations for TS-TMVR; of whom, 58.1% were women. The proportion of women among those undergoing TS-TMVR increased from 50% in 2015 to 60.2% in 2018 (Ptrend = 0.04). Compared with men, women undergoing TS-TMVR were slightly younger, and had a distinct profile of comorbidities. After matching, there was no significant difference in in-hospital mortality among women versus men undergoing TS-TMVR (7.8% vs. 6.1%, OR = 1.30; 95% CI: 0.79-2.13). Subgroup analyzes showed an interaction toward higher mortality with women versus men among patients with CKD (Pinteraction = 0.07). There were no significant differences between women and men in in-hospital complications or length of stay after TS-TMVR. Compared with men, women undergoing TS-TMVR were more likely to be discharged to a nursing facility (17.7% vs. 11.5%, p = 0.01) and had higher rates of 30-day readmissions (22.4% vs. 13.6%, p = 0.01). CONCLUSION: This nationwide analysis showed an increase in the proportion of women among patients undergoing TS-TMVR during the study years. There were no differences in in-hospital mortality, in-hospital complications, or length of stay between both sexes following TS-TMVR. Women were more likely to be discharged to nursing facilities and had higher rates of readmission at 30 days even after propensity matching.

Prevalence of Coronary Endothelial and Microvascular Dysfunction in Women with Symptoms of Ischemia and No Obstructive Coronary Artery Disease Is Confirmed by a New Cohort: The NHLBI-Sponsored Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD).

OBJECTIVE: In a separate, contemporary cohort, we sought to confirm findings of the original Women's Ischemia Syndrome Evaluation (WISE). BACKGROUND: The original WISE observed a high prevalence of both invasively determined coronary endothelial and coronary microvascular dysfunction (CMD) that predicted adverse events in follow-up. METHODS: We comparatively studied the WISE-Coronary Vascular Dysfunction (CVD) cohort (2009-2011), with signs and symptoms of ischemia but without significant CAD, to the original WISE (1997-2001) cohort. CMD was defined as coronary flow reserve (CFR) ≤2.5, or endothelial dysfunction as epicardial coronary artery constriction to acetylcholine (ACH), or <20% epicardial coronary dilation to nitroglycerin (NTG). RESULTS: In WISE (n=181) and WISE-CVD (n=235) women, mean age in both was 54 years, and 83% were white (WISE) vs 74% (WISE-CVD, p=0.04). Use of hormone replacement therapy was less frequent in WISE-CVD vs WISE (46% vs 57%, p=0.026) as was presence of hypertension (40% vs 52%, p=0.013), hyperlipidemia (20% vs 46%, p<0.0001), and smoking (46% vs 56%, p=0.036). Similar rates were observed in WISE-CVD and WISE cohorts for CMD (mean CFR 2.7±0.6 vs 2.6±0.8, p=0.35), mean change in diameter with intracoronary ACH (0.2±10.0 vs 1.6±12.8 mm, p=0.34), and mean change in diameter with intracoronary NTG (9.7±13.0 vs 9.8±13.5 mm, p=0.94), respectively. CONCLUSIONS: This study confirms prevalence of CMD in the contemporary WISE-CVD cohort similar to that of the original WISE cohort, despite a lower risk factor burden in WISE-CVD. Because these coronary functional abnormalities predict major adverse cardiac events, clinical trials of therapies targeting these abnormalities are indicated.

Predictors of patient radiation exposure during transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) exposes patients to radiation. OBJECTIVES: We sought to identify factors associated with higher radiation exposure and to quantify their relative influence, which may inform reduction of this hazard. METHODS: All TAVR procedures at Rhode Island Hospital between March 20, 2012 and February 12, 2017 were included. Procedures were performed by two co-primary operators using a Siemens Artis Zeego system. Radiation metrics were generated by the imaging system. The primary metric was dose-area product (DAP, Gy*cm2 ), and secondary metrics were reference point air kerma (mGy) and fluoroscopy time (minutes). Data collected for the STS/ACC TVT Registry were utilized to develop a multivariable linear regression model predicting DAP. RESULTS: In 294 TAVRs, median DAP was 169 Gy*cm2 [interquartile range (IQR) 106-238]. The r2 values for the full 27-variable DAP model and reduced eight-variable model were 0.457 and 0.420, respectively. Valve area, aortic insufficiency, and procedure year (suggesting absence of a learning curve) were non-significant predictors in the full model, while increasing weight, cutdown transfemoral access, higher pre-procedure creatinine and hemoglobin, and vascular complications predicted higher DAP in both models. Results were unchanged when DAP was log-transformed. Secondary models for air kerma and fluoroscopy time revealed similar predictors. CONCLUSION: Factors associated with increased procedural complexity and duration as well as radiation attenuation and scatter predict increased patient radiation exposure during TAVR. Modification of procedural technique, especially using percutaneous femoral vascular access, may facilitate reduction in exposure.

Vascular complications associated with transcatheter aortic valve replacement.

Transcatheter aortic valve replacement (TAVR) is now an accepted pathway for aortic valve replacement for patients who are at prohibitive, severe and intermediate risk for traditional aortic valve surgery. However, with this rising uptrend and adaptation of this new technology, vascular complications and their management remain an Achilles heel for percutaneous aortic valve replacement. The vascular complications are an independent predictor of mortality for patients undergoing TAVR. Early recognition of these complications and appropriate management is paramount. In this article, we review the most commonly encountered vascular complications associated with currently approved TAVR devices and their optimal percutaneous management techniques.

Aldosterone inhibition and coronary endothelial function in women without obstructive coronary artery disease: an ancillary study of the national heart, lung, and blood institute-sponsored women's ischemia syndrome evaluation.

UNLABELLED: Endothelial dysfunction is highly prevalent and associated with adverse outcomes among patients without obstructive coronary artery disease (CAD). Angiotensin II inhibition may improve endothelial function, but with continued treatment, "aldosterone escape" may occur. Thus, it is unknown if adding aldosterone blockade further improves endothelial function. METHODS: In a double-blind, parallel-group, repeated-measures study, women with symptoms and signs of ischemia, no significant CAD, and coronary endothelial dysfunction receiving an angiotensin-converting enzyme inhibitor or receptor blocker were randomized to aldosterone blockade or placebo. The primary outcome at 16 weeks was percent change in coronary diameter to acetylcholine, and secondary outcome, coronary flow reserve to adenosine, both adjusted for baseline reactivity. RESULTS: Forty-one women completed the treatment period with repeat coronary reactivity testing. Their mean age was 54 ± 10 years; body mass index, 30 ± 7.4 kg/m2; 12% had diabetes; and 15% had metabolic syndrome. There were no significant differences between treatment groups. At baseline, the percent change in reference vessel coronary diameter to acetylcholine was -5.0% in the aldosterone blockade group and -3.4% in the placebo group and, at 16 weeks, -7.2% in the aldosterone blockade group versus -14.3% in the placebo group (P = .15). At 16 weeks, the change in coronary flow reserve to intracoronary adenosine was -0.13 in the aldosterone blockade group versus -0.25 in the placebo group (P = .66). CONCLUSION: Adding aldosterone receptor blockade to angiotensin II inhibition did not improve coronary endothelial or microvascular function among women with signs and symptoms of ischemia in the setting of nonobstructive CAD.

Adverse outcomes among women presenting with signs and symptoms of ischemia and no obstructive coronary artery disease: findings from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) angiographic core laboratory.

BACKGROUND: Women presenting with signs and symptoms of myocardial ischemia frequently have no or nonobstructive coronary artery disease (CAD). OBJECTIVE: This study aimed to investigate the associations between angiographic measures and longer-term clinical outcomes among women with signs and symptoms of ischemia referred for coronary angiography. METHODS: A prospective cohort analysis of women referred for coronary angiography and enrolled in the National Heart, Lung, and Blood Institute-sponsored WISE was performed. An angiographic severity score was prospectively developed, assigning points for any stenosis weighted by stenosis severity, location, and collaterals and was then tested for prediction for adverse outcome in 917 women, over a median of 9.3 years. SETTING: The study was conducted in referral centers. PATIENTS: Women with signs and/or symptoms of myocardial ischemia referred for coronary angiography were consecutively consented and enrolled in a prospective study. MAIN OUTCOME MEASURES: Main outcomes included first occurrence of cardiovascular death or nonfatal myocardial infarction. Hospitalization for angina was a secondary outcome. RESULTS: Cardiovascular death or myocardial infarction at 10 years occurred in 6.7%, 12.8%, and 25.9% of women with no, nonobstructive, and obstructive CAD (P < .0001), respectively. Cumulative 10-year cardiovascular death or myocardial infarction rates showed progressive, near-linear increases for each WISE CAD severity score range of 5, 5.1 to 10, 10.1 to 20, 20.1 to 50, and >50. The optimal threshold in the WISE severity score classifications for predicting cardiovascular mortality was >10 (eg, 5.0-10 vs 10.1-89), with both a sensitivity and specificity of 0.64 and an area under the curve of 0.64 (P = .02, 95% CI 0.59-0.68). CONCLUSIONS: Among women with signs and symptoms of ischemia, nonobstructive CAD is common and associated with adverse outcomes over the longer term. The new WISE angiographic score appears to be useful for risk prediction in this population.

Mitral Valve Transcatheter Edge-to-Edge Repair After TAVR: A Nationwide Analysis.

Patients with persistent severe mitral regurgitation after transcatheter aortic valve replacement (TAVR) may benefit from mitral transcatheter edge-to-edge repair (M-TEER). Using the Nationwide Readmission Database, we identified patients who had M-TEER within 6 months after TAVR and compared their outcomes with patients who had M-TEER without previous recent TAVR during the same calendar year between 2014 and 2020. Because Nationwide Readmission Database data do not cross years, analysis was restricted to the last half of each calendar year. End points included in-hospital mortality and 30-day and 90-day postdischarge rehospitalization rates. In 23,885 M-TEER patients, 396 (1.7%) had a previous recent TAVR. The number of post-TAVR M-TEER procedures increased progressively over time from 16 in 2014 to 92 in 2020. Patients who had M-TEER after a recent TAVR versus those without previous TAVR had similar in-hospital mortality (adjusted odds ratio 0.38, 95% confidence interval [CI] 0.12 to 1.23, p = 0.11), but higher rates of 30-day all-cause hospitalization and heart failure hospitalization (adjusted odds ratios 1.34, 95% CI 1.11 to 1.79, p = 0.04 and 1.63, 95% CI 1.13 to 2.36, p = 0.009, respectively). Nonetheless, in patients who underwent M-TEER post-TAVR, the cumulative 90-day all-cause hospitalization and heart failure hospitalization rates were less after M-TEER compared with before M-TEER (from 45.7% to 31.5%, p = 0.007, and from 29.0% to 16.6%, respectively, both p = 0.005). In conclusion, M-TEER procedures after TAVR in the United States are increasing. Patients with M-TEER after TAVR had similar in-hospital mortality as those who underwent M-TEER without recent TAVR, but higher 30-day hospitalization rates. Nonetheless, 90-day hospitalization rates were decreased after M-TEER in patients with previous TAVR.

In-hospital and Readmission Outcomes With Percutaneous Balloon Mitral Valvuloplasty.

Percutaneous balloon mitral valvuloplasty (PBMV) is primarily performed for rheumatic mitral stenosis (MS). Therefore, limited data exist on PBMV in countries with a low incidence of rheumatic disease. Using the Nationwide Readmission Database, we examined trends in in-hospital mortality and 30-day readmission among patients who received PBMV for rheumatic and non-rheumatic MS. We also examined the change in 90-day hospitalization rate before vs after PBMV. Between 2016 and 2019, there were 1109 hospitalizations in which patients received PBMV for rheumatic (n = 955, 86.1%) vs non-rheumatic MS (n = 154, 13.9%). The all-cause in-hospital mortality for rheumatic and non-rheumatic MS did not change over time (0.9% → 2.0%, P = 0.94, and 5.9% → 9.5%, P = 0.09 respectively). Similarly, the 30-day readmission for patients with rheumatic and non-rheumatic MS did not change over time (12.4% → 9.9%, P = 0.26, and 4.4% → 10.5%, P = 0.30, respectively). The 90-day all-cause hospitalization rate remained the same before vs after PBMV for rheumatic and non-rheumatic MS (25.5% → 21.8%; P = 0.14, and 24.0% → 33.7%; P = 0.19, respectively). Although no statistically significant change was noted over time for trends in in-hospital mortality, 30-day readmission, or even in the change in 90-day all-cause hospitalizations before and after PBMV for both types of MS, among those with non-rheumatic MS, there was a signal of an increase in the in-hospital mortality, and 30-day readmission, even more, there was 29% relative increase in 90-day hospitalizations after PBMV. Future studies are needed to examine the role of PBMV in patients with non-rheumatic MS.

Association of anti-oxidized LDL and candidate genes with severity of coronary stenosis in the Women's Ischemia Syndrome Evaluation study.

Atherosclerosis is the major cause of coronary artery disease (CAD), and oxidized LDL (oxLDL) is believed to play a key role in the initiation of the atherosclerotic process. Recent studies show that inflammation and autoimmune reactions are also relevant in atherosclerosis. In this study, we examined the association of antibodies against oxLDL (anti-oxLDL) with the severity of CAD in 558 Women's Ischemia Syndrome Evaluation (WISE) study samples (465 whites; 93 blacks) determined by coronary stenosis (< 20%, 20%-49%, > 50% stenosis). We also examined the relationship of anti-oxLDL with serum lipid levels and nine candidate genes including APOE, APOH, APOA5, LPL, LRP1, HL, CETP, PON1, and OLR1. IgM anti-oxLDL levels were significantly higher in the >20% stenosis group than in the ≥ 20% stenosis group in whites (0.69 ± 0.02 vs. 0.64 ± 0.01, respectively; P = 0.02). IgM anti-oxLDL levels correlated significantly with total cholesterol (r² = 0.01; P = 0.03) and LDL cholesterol (r² = 0.017; P = 0.004) in whites. Multiple regression analysis revealed a suggestive association of LPL/S447X single-nucleotide polymorphism (SNP) with both IgG anti-oxLDL (P = 0.02) and IgM anti-oxLDL (P = 0.07), as well as between IgM anti-oxLDL and the OLR1/3'UTR SNP (P = 0.020). Our data suggest that higher IgM anti-oxLDL levels may provide protection against coronary stenosis and that genetic variation in some candidate genes are determinants of anti-oxLDL levels.

In women with symptoms of cardiac ischemia, nonobstructive coronary arteries, and microvascular dysfunction, angiotensin-converting enzyme inhibition is associated with improved microvascular function: A double-blind randomized study from the National Heart, Lung and Blood Institute Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND: We investigated the role of the renin-angiotensin system in women with signs and symptoms of ischemia without obstructive coronary artery disease (CAD). Although microvascular dysfunction has been suggested to explain this syndrome and recently was found to predict adverse outcomes, the mechanisms and treatments remain unclear. METHODS: In a substudy within the WISE, 78 women with microvascular dysfunction (coronary flow reserve [CFR] <3.0 following adenosine) and no obstructive CAD were randomly assigned to either an angiotensin-converting enzyme inhibition (ACE-I) with quinapril or a placebo treatment group. The primary efficacy parameter was CFR at 16 weeks adjusted for baseline characteristics and clinical site. The secondary response variable was freedom from angina symptoms assessed using the Seattle Angina Questionnaire. RESULTS: A total of 61 women completed the 16-week treatment period with repeat CFR measurements, and treatment was well tolerated. For the primary outcome, at 16 weeks, CFR improved more with ACE-I than placebo (P < .02). For the secondary outcome of symptom improvement, ACE-I treatment (P = .037) and CFR increase (P = .008) both contributed. CONCLUSIONS: Microvascular function improves with ACE-I therapy in women with signs and symptoms of ischemia without obstructive CAD. This improvement is associated with reduction in angina. The beneficial response of the coronary microvasculature was limited to women with lower baseline CFR values, suggesting that the renin-angiotensin system may be more involved among women with more severe microvascular defects.

A randomized controlled trial of low-dose hormone therapy on myocardial ischemia in postmenopausal women with no obstructive coronary artery disease: results from the National Institutes of Health/National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND: Compared with men, women have more evidence of myocardial ischemia with no obstructive coronary artery disease. Although low endogenous estrogen levels are associated with endothelial dysfunction, the role of low-dose hormone therapy has not been fully evaluated. We postulate that a 12-week duration of low-dose hormone replacement therapy is associated with myocardial ischemia and endothelial dysfunction. METHODS AND RESULTS: Using a multicenter, randomized, placebo-controlled design, subjects were randomized to receive either 1 mg norethindrone/10 microg ethinyl estradiol or placebo for 12 weeks. Chest pain and menopausal symptoms, cardiac magnetic resonance spectroscopy, brachial artery reactivity, exercise stress testing, and psychosocial questionnaires were evaluated at baseline and exit. Recruitment was closed prematurely because of failure to recruit after publication of the Women's Health Initiative hormone trial. Of the 35 women who completed the study, there was less frequent chest pain in the treatment group compared with the placebo group (P = .02) at exit. Women taking 1 mg norethindrone/10 microg ethinyl estradiol also had significantly fewer hot flashes/night sweats (P = .003), less avoidance of intimacy (P = .05), and borderline differences in sexual desire and vaginal dryness (P = .06). There were no differences in magnetic resonance spectroscopy, brachial artery reactivity, compliance, or reported adverse events between the groups. CONCLUSIONS: These data suggest that low-dose hormone therapy improved chest pain symptoms, menopausal symptoms, and quality of life, but did not improve ischemia or endothelial dysfunction. Given that it was not possible to enroll the prespecified sample size, these results should not be considered definitive.

An intravascular ultrasound analysis in women experiencing chest pain in the absence of obstructive coronary artery disease: a substudy from the National Heart, Lung and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE).

AIMS: Using intravascular ultrasound (IVUS), we sought to characterize coronary morphology in women with chest pain without major epicardial obstructive coronary artery disease (CAD). We have previously observed an unexpectedly high rate of adverse outcomes among women with chest pain and normal or insignificant obstructive CAD. Information about the presence and characteristics of coronary atherosclerosis in these women could provide insight into the mechanisms related to increased risk, as well as improved diagnosis, prevention, and treatment. METHODS: Women (n = 100) with suspected ischemia without obstructive CAD (>50% stenosis) underwent IVUS of a left coronary segment with measurements by a core lab masked to clinical and angiographic findings. RESULTS: Angiograhic core lab analysis found 69.6% of patients had no (≤20%) and 30.4% had minimal (20-<50%) CAD. IVUS segmental images were interpretable by the core lab in 92 women, with 19 (21%) having no atherosclerosis (intimal-medial thickness <0.5 mm). In the remaining 73 women (79%), percent atheroma volume was 27 ± 8% and mean maximum plaque thickness was 0.53 ± 0.22 mm. Thirty-eight women with atherosclerosis (53%) had ≥30% of interrogated vessel involved. The average vessel involvement was 40%, and the maximum plaque thickness was 1.27 mm. The number of risk factors strongly correlated with percent atheroma volume (r = 0.53, P < 0.0001) and percent vessel involvement (r = 0.51, P < 0.0001), with the strongest independent predictor of both being age. Remodeling was assessed in 59/73 women (81%), and 73% had evidence of positive remodeling. CONCLUSIONS: In symptomatic women without significant luminal obstructive CAD, we observed a high prevalence of atherosclerosis with positive remodeling and preserved lumen size. These findings may help explain increased risk and emphasize need for improved diagnostic and treatment options for women with concealed CAD.

Trends and outcomes of red blood cell transfusion in patients undergoing transcatheter aortic valve replacement in the United States.

OBJECTIVES: To examine temporal trends, predictors, and outcomes of red blood cell (RBC) transfusion in patients undergoing transcatheter aortic valve replacement (TAVR) in the United States. METHODS: We used the National Inpatient Sample databases to identify TAVR procedures performed between January 2012 and September 2015 in the United States. Patients were propensity matched (within the strata of overt and no bleeding) on the likelihood of receiving RBC transfusion, and in-hospital outcomes were compared between the 2 groups in the matched cohort. RESULTS: Among 46,710 TAVR procedures performed during the study period, rates of RBC transfusion were 17.3% (95% confidence interval [CI], 16.1%-18.5%). RBC transfusion rates decreased significantly from 29.5% during the first quarter of 2012 to 10.8% during the third quarter of 2015 (P < .001). Older age, female sex, peripheral vascular disease, chronic kidney disease, anemia, coagulopathy, and fluid/electrolyte disorders were associated with increased odds, whereas elective admission, obesity, and endovascular access were associated with decreased odds of RBC transfusion. In the propensity-matched cohort (7995 pairs with and without RBC transfusion), RBC transfusion was associated with increased risk of in-hospital mortality, infection, and transient ischemic attack/stroke in patients without bleeding (odds ratio [OR]Mortality, 2.29; 95% CI, 1.31-4.02; ORInfection, 2.13; 95% CI, 1.03-4.39; ORTransient ischemic attack/Stroke, 3.36; 95% CI, 1.52-7.45), but not in those with overt bleeding (ORMortality, 1.10; 95% CI, 0.68-1.48; ORInfection, 0.80; 95% CI, 0.45-1.45; ORTransient ischemic attack/Stroke, 1.16; 95% CI, 0.74-1.85); Pinteraction < .05 for all. CONCLUSIONS: RBC transfusion is associated with worse clinical outcomes in TAVR patients without bleeding, but not in those with overt bleeding. The utility and optimal threshold for RBC transfusion in TAVR patients, especially among those with overt bleeding, warrants further prospective investigation.

Multimarker approach predicts adverse cardiovascular events in women evaluated for suspected ischemia: results from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation.

BACKGROUND: Inflammatory marker and hemoglobin levels (eg biomarkers) considered separately, predict adverse events in selected populations. HYPOTHESIS: A multiple biomarker approach predicts adverse events in women referred for evaluation of ischemia. METHODS: We investigated associations between biomarkers (high sensitivity C-reactive protein, interleukin-6, serum amyloid-A, and hemoglobin levels) with adverse outcomes in women referred for coronary angiography for suspected ischemia in the National Heart, Lung, and Blood Institute (NHLBI)-sponsored Women's Ischemia Syndrome Evaluation (WISE). RESULTS: Among 595 women (mean age 58 years, ejection fraction [EF] 65%, majority without coronary stenosis >or= 50%) followed for 3.6 +/- 1.8 years (mean +/- SD), those without abnormal markers had fewer events (11.6%) compared to those with 1 (18.4%), 2 (20.9%), or 3 (37%) abnormal markers (p < 0.001 for trend). Women without abnormal markers had fewer deaths (1.6%) than women with 1 (6.1%), 2 (9.1%), or 3 (17%) abnormal markers (p < 0.001 for trend). Adding low hemoglobin was associated with higher adverse event and all-cause mortality rates. In multivariate analysis, as the number of abnormal biomarkers increased risk increased. Women with 3 or 4 abnormal biomarkers were approximately 10-20 times more likely to die (p < 0.05). Biomarkers added to the predictive information provided by the Framingham Risk Score. CONCLUSIONS: Among women undergoing coronary angiography for suspected ischemia, a multibiomarker approach predicted adverse events. Biomarkers added prognostic information beyond that obtained from traditional risk factors.

Association Between Red Blood Cell Transfusion and Clinical Outcomes Among Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: We evaluated the association between postprocedural packed red blood cell transfusion and morbidity and mortality among patients undergoing transcatheter aortic valve replacement. METHODS: We retrospectively analyzed 429 patients with severe aortic stenosis who underwent transcatheter aortic valve replacement. Propensity-score adjusted multivariable logistic and Cox regression models were used to determine the association of packed red blood cell transfusion with the composite endpoint of death, myocardial infarction, and stroke at 30 days and in hospital, and 1-year mortality. RESULTS: Patients receiving transfusions had a higher 30-day and in-hospital incidence of death, myocardial infarction, or stroke when compared with patients who did not receive transfusions (hazard ratio 2.03, 95% confidence interval: 1.02 to 4.07, p = 0.045; and hazard ratio 2.46, 95% confidence interval: 1.12 to 5.41, p = 0.025, respectively). Postprocedural transfusion was independently associated with 1-year mortality (hazard ratio 2.65, 95% confidence interval: 1.21 to 5.80, p = 0.015). CONCLUSIONS: Packed red blood cell transfusion for patients undergoing transcatheter aortic valve replacement is associated with an increased incidence of adverse outcomes during hospitalization and at 30-day and 1-year follow-up.

Adrenergic gene polymorphisms and cardiovascular risk in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation.

BACKGROUND: Adrenergic gene polymorphisms are associated with cardiovascular and metabolic phenotypes. We investigated the influence of adrenergic gene polymorphisms on cardiovascular risk in women with suspected myocardial ischemia. METHODS: We genotyped 628 women referred for coronary angiography for eight polymorphisms in the alpha1A-, beta1-, beta2- and beta3-adrenergic receptors (ADRA1A, ADRB1, ADRB2, ADRB3, respectively), and their signaling proteins, G-protein beta 3 subunit (GNB3) and G-protein alpha subunit (GNAS). We compared the incidence of death, myocardial infarction, stroke, or heart failure between genotype groups in all women and women without obstructive coronary stenoses. RESULTS: After a median of 5.8 years of follow-up, 115 women had an event. Patients with the ADRB1 Gly389 polymorphism were at higher risk for the composite outcome due to higher rates of myocardial infarction (adjusted hazard ratio [HR] 3.63, 95% confidence interval [95%CI] 1.17-11.28; Gly/Gly vs. Arg/Arg HR 4.14, 95%CI 0.88-19.6). The risk associated with ADRB1 Gly389 was limited to those without obstructive CAD (n = 400, Pinteraction = 0.03), albeit marginally significant in this subset (HR 1.71, 95%CI 0.91-3.19). Additionally, women without obstructive CAD carrying the ADRB3 Arg64 variant were at higher risk for the composite endpoint (HR 2.10, 95%CI 1.05-4.24) due to subtle increases in risk for all of the individual endpoints. No genetic associations were present in women with obstructive CAD. CONCLUSION: In this exploratory analysis, common coding polymorphisms in the beta1- and beta3-adrenergic receptors increased cardiovascular risk in women referred for diagnostic angiography, and could improve risk assessment, particularly for women without evidence of obstructive CAD. TRIAL REGISTRATION: ClinicalTrials.gov NCT00000554.

Comparison of Incidence, Predictors, and Outcomes of Early Infective Endocarditis after Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement in the United States.

Infective endocarditis (IE) of prosthetic or bioprosthetic heart valves is a serious complication associated with significant morbidity and mortality. Data on the incidence, risk factors, and outcomes of IE after transcatheter aortic valve implantation (TAVI) in the United States are limited. We used the 2013 to 2014 Nationwide Readmissions Databases to determine the incidence of early IE after TAVI and surgical aortic valve replacement (SAVR) in the US. Clinical characteristics, independent predictors, and outcomes of patients with IE post-TAVI were examined. In 29,306 TAVI and 66,077 SAVR patients, the incidence rates of early IE were 1.7% (95% confidence interval [CI] 1.5% to 1.9%) and 2.5% (95% CI 2.3% to 2.9%) per person-year, respectively. In a propensity-matched cohort of 15,138 TAVI and 15,030 SAVR patients (weighted), there were no significant differences in the incidence rates of IE (1.7% [95% CI 1.4% to 2.0%] vs 1.9% [95% CI 1.6% to 2.2%] per person-year, log-rank p = 0.29) or in the median (interquartile range) time to IE (91 [48 to 146] vs 92 [61 to 214] days, p = 0.13). Staphylococcus (30.4%), Streptococcus (29.9%), and Enterococcus (20.5%) were the most common causative organisms of IE post-TAVI. Younger age, history of heart failure, need for permanent pacemaker placement, cardiac arrest, major bleeding, and sepsis during the index TAVI hospitalization were independently associated with an increased risk of IE. In-hospital mortality rate during readmission for IE was 15.6%. In conclusion, in a nationally representative cohort of TAVI patients in the US, the incidence rate of early IE was 1.7% per person-year. Age, co-morbid conditions, invasive procedures, and complications during the index hospitalization were associated with incident IE post-TAVI.

Extent of coronary atherosclerosis and arterial remodelling in women: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation.

BACKGROUND: Information regarding the pathogenesis of ischemic heart disease (IHD) in women is limited. Sex-specific responses to atherosclerosis and coronary arterial remodelling in women versus men have been hypothesized, but limited study exists. METHODS: Case-matched study of 174 women with suspected ischemia referred for coronary angiography: 87 with non-obstructive coronary artery disease (CAD) (no luminal diameter stenosis >20% in any coronary artery) and 87 age and ethnicity matched women with obstructive CAD. Groups were compared with regard to atheroma burden and coronary arterial remodelling assessed by coronary artery intravascular ultrasound (IVUS). RESULTS: IVUS revealed more extensive atheroma with obstructive CAD vs. those without obstructive CAD, with greater percent atheroma volume (PAV) (36.1%±9.8% vs. 25.4%±9.1%, P<0.0001), total atheroma volume (TAV) (140.8±58.7 vs. 98.8±46.9 mm3, P<0.0001) and percentage of images containing plaque (70.0%±30.5% vs. 35.7%±32.6%, P<0.0001). Adjusting for risk factors, PAV (35%±1% vs. 28%±1%, P=0.0008), TAV (131±7 vs. 115±7 mm3, P=0.110) and percentage of images containing plaque (66%±4% vs. 45%±5%, P=0.0008) remained greater with obstructive CAD. Obstructive CAD was associated with smaller lumen volumes (251.9±92.8 vs. 289.7±91.8 mm3, P=0.005), but surprisingly, the external elastic membrane (EEM) volume was very similar comparing the groups (392.7±128.1 vs. 388.6±113.7 mm3, P=0.910). CONCLUSIONS: Our findings suggest that women referred to angiography for suspected ischemia, have differing patterns of coronary arterial response to injury with regard to accumulation of atherosclerosis and compensatory remodelling related to the presence and absence of obstructive CAD. Preservation and cultivation of compensatory arterial remodelling may be a novel CAD therapeutic target.

Outcomes Following Urgent/Emergent Transcatheter Aortic Valve Replacement: Insights From the STS/ACC TVT Registry.

OBJECTIVES: The authors sought to examine outcomes and identify independent predictors of mortality among patients undergoing urgent/emergent transcatheter aortic valve replacement (TAVR). BACKGROUND: Data on urgent/emergent TAVR as a rescue therapy for decompensated severe aortic stenosis (AS) are limited. METHODS: The Society of Thoracic Surgeons and the American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) Registry linked with Centers for Medicare & Medicaid Services claims was used to identify patients who underwent urgent/emergent versus elective TAVR between November 2011 and June 2016. Outcomes assessed were device success rate, in-hospital major adverse events, and 30-day and 1-year mortality. Independent predictors of mortality after urgent/emergent TAVR were examined. RESULTS: Of 40,042 patients who underwent TAVR, 3,952 (9.9%) were urgent/emergent (median STS PROM score 11.8 [interquartile range: 7.6 to 17.9]). Device success rate was statistically lower, but not clinically different after urgent/emergent versus elective TAVR (92.6% vs. 93.7%; p = 0.007). Rates of major and/or life-threatening bleeding, major vascular complications, myocardial infarction, stroke, new permanent pacemaker placement, conversion to SAVR, and paravalvular regurgitation were similar between the 2 groups. Compared with elective TAVR, patients undergoing urgent/emergent TAVR had higher rates of acute kidney injury and/or new dialysis (8.2% vs. 4.2%; p < 0.001), 30-day mortality (8.7% vs. 4.3%, adjusted hazard ratio: 1.28, 95% confidence interval: 1.10 to 1.48), and 1-year mortality (29.1% vs. 17.5%, adjusted hazard ratio: 1.20, 95% confidence interval: 1.10 to 1.31). In patients undergoing urgent/emergent TAVR, non-femoral access and cardiopulmonary bypass were associated with increased risk, whereas use of balloon-expandable valve was associated with decreased risk of 30-day and 1-year mortality. CONCLUSIONS: Urgent/emergent TAVR is feasible with acceptable outcomes and may be a reasonable option in a selected group of patients with severe AS.

The economic burden of angina in women with suspected ischemic heart disease: results from the National Institutes of Health--National Heart, Lung, and Blood Institute--sponsored Women's Ischemia Syndrome Evaluation.

BACKGROUND: Coronary angiography is one of the most frequently performed procedures in women; however, nonobstructive (ie, < 50% stenosis) coronary artery disease (CAD) is frequently reported. Few data exist regarding the type and intensity of resource consumption in women with chest pain after coronary angiography. METHODS AND RESULTS: A total of 883 women referred for coronary angiography were prospectively enrolled in the National Institutes of Health--National Heart, Lung, and Blood Institute--sponsored Women's Ischemia Syndrome Evaluation (WISE). Cardiovascular prognosis and cost data were collected. Direct (hospitalizations, office visits, procedures, and drug utilization) and indirect (out-of-pocket, lost productivity, and travel) costs were estimated through 5 years of follow-up. Among 883 women, 62%, 17%, 11%, and 10% had nonobstructive and 1-vessel, 2-vessel, and 3-vessel CAD, respectively. Five-year cardiovascular death or myocardial infarction rates ranged from 4% to 38% for women with nonobstructive to 3-vessel CAD (P < 0.0001). Five-year rates of hospitalization for chest pain occurred in 20% of women with nonobstructive CAD, increasing to 38% to 55% for women with 1-vessel to 3-vessel CAD (P < 0.0001). The volume of repeat catheterizations or angina hospitalizations was 1.8-fold higher in women with nonobstructive versus 1-vessel CAD after 1 year of follow-up (P < 0.0001). Drug treatment was highest for those with nonobstructive or 1-vessel CAD (P < 0.0001). The proportion of costs for anti-ischemic therapy was higher for women with nonobstructive CAD (15% versus 12% for 1-vessel to 3-vessel CAD; P = 0.001). For women with nonobstructive CAD, average lifetime cost estimates were $767,288 (95% CI, $708,480 to $826,097) and ranged from $1,001,493 to $1,051,302 for women with 1-vessel to 3-vessel CAD (P = 0.0003). CONCLUSIONS: Symptom-driven care is costly even for women with nonobstructive CAD. Our lifetime estimates for costs of cardiovascular care identify a significant subset of women who are unaccounted for within current estimates of the economic burden of coronary heart disease.