Impact of Moderate Aortic Stenosis in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Afterload from moderate aortic stenosis (AS) may contribute to adverse outcomes in patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: The authors evaluated clinical outcomes in patients with HFrEF and moderate AS relative to those without AS and with severe AS. METHODS: Patients with HFrEF, defined by left ventricular ejection fraction (LVEF) <50% and no, moderate, or severe AS were retrospectively identified. The primary endpoint, defined as a composite of all-cause mortality and heart failure (HF) hospitalization, was compared across groups and within a propensity score-matched cohort. RESULTS: We included 9,133 patients with HFrEF, of whom 374 and 362 had moderate and severe AS, respectively. Over a median follow-up time of 3.1 years, the primary outcome occurred in 62.7% of patients with moderate AS vs 45.9% with no AS (P < 0.0001); rates were similar with severe and moderate AS (62.0% vs 62.7%; P = 0.68). Patients with severe AS had a lower incidence of HF hospitalization (36.2% vs 43.6%; P < 0.05) and were more likely to undergo AVR within the follow-up period. Within a propensity score-matched cohort, moderate AS was associated with an increased risk of HF hospitalization and mortality (HR: 1.24; 95% CI: 1.04-1.49; P = 0.01) and fewer days alive outside of the hospital (P < 0.0001). Aortic valve replacement (AVR) was associated with improved survival (HR: 0.60; CI: 0.36-0.99; P < 0.05). CONCLUSIONS: In patients with HFrEF, moderate AS is associated with increased rates of HF hospitalization and mortality. Further investigation is warranted to determine whether AVR in this population improves clinical outcomes.

Racial and Ethnic Differences in the Clinical Diagnosis of Aortic Stenosis.

Background Racial and ethnic minority groups are underrepresented among patients undergoing aortic valve replacement in the United States. We evaluated the impact of race and ethnicity on the diagnosis of aortic stenosis (AS). Methods and Results In patients with transthoracic echocardiography (TTE)-confirmed AS, we assessed rates of AS diagnosis as defined by assignment of an International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) code for AS within a large multicenter electronic health record. Multivariable Cox proportional hazard and competing risk regression models were used to evaluate the 1-year rate of AS diagnosis by race and ethnicity. Among 14 800 patients with AS, the 1-year diagnosis rate for AS following TTE was 37.4%. Increasing AS severity was associated with an increased likelihood of receiving an AS diagnosis (moderate: hazard ratio [HR], 3.05 [95% CI, 2.86-3.25]; P<0.0001; severe: HR, 4.82 [95% CI, 4.41-5.28]; P<0.0001). Compared with non-Hispanic White, non-Hispanic Black (HR, 0.65 [95% CI, 0.54-0.77]; P<0.0001) and non-Hispanic Asian individuals (HR, 0.72 [95% CI, 0.57-0.90], P=0.004) were less likely to receive a diagnosis of AS. Additional factors associated with a decreased likelihood of receiving an AS diagnosis included a noncardiology TTE ordering provider (HR, 0.92 [95% CI, 0.86-0.97]; P=0.005) and TTE performed in the inpatient setting (HR, 0.72 [95% CI, 0.66-0.78]; P<0.0001). Conclusions Rates of receiving an ICD diagnostic code for AS following a diagnostic TTE are low and vary significantly by race and ethnicity and disease severity. Further studies are needed to determine if efforts to maximize the clinical recognition of TTE-confirmed AS may help to mitigate disparities in treatment.

Trends in Utilization of Aortic Valve Replacement for Severe Aortic Stenosis.

BACKGROUND: Despite the rapid growth of aortic valve replacement (AVR) for aortic stenosis (AS), limited data suggest symptomatic severe AS remains undertreated. OBJECTIVES: This study sought to investigate temporal trends in AVR utilization among patients with a clinical indication for AVR. METHODS: Patients with severe AS (aortic valve area <1 cm2) on transthoracic echocardiograms from 2000 to 2017 at 2 large academic medical centers were classified based on clinical guideline indications for AVR and divided into 4 AS subgroups: high gradient with normal left ventricular ejection fraction (LVEF) (HG-NEF), high gradient with low LVEF (HG-LEF), low gradient with normal LVEF (LG-NEF), and low gradient with low LVEF (LG-LEF). Utilization of AVR was examined and predictors identified. RESULTS: Of 10,795 patients, 6,150 (57%) had an indication or potential indication for AVR, of whom 2,977 (48%) received AVR. The frequency of AVR varied by AS subtype with LG groups less likely to receive an AVR (HG-NEF: 70%, HG-LEF: 53%, LG-NEF: 32%, LG-LEF: 38%, P < 0.001). AVR volumes grew over the 18-year study period but were paralleled by comparable growth in the number of patients with an indication for AVR. In patients with a Class I indication, younger age, coronary artery disease, smoking history, higher hematocrit, outpatient index transthoracic echocardiogram, and LVEF ≥0.5 were independently associated with an increased likelihood of receiving an AVR. AVR was associated with improved survival in each AS-subgroup. CONCLUSIONS: Over an 18-year period, the proportion of patients with an indication for AVR who did not receive AVR has remained substantial despite the rapid growth of AVR volumes.

Relation of Subacute Kidney Injury to Mortality After Transcatheter Aortic Valve Implantation.

Acute kidney injury after transcatheter aortic valve implantation (TAVI) has been associated with adverse outcomes; however, data are limited on the subacute changes in renal function that occur after discharge and their impact on clinical outcomes. This study investigates the relation between subacute changes in kidney function at 30 days after TAVI and survival. Patients from 2 centers who underwent TAVI and survived beyond 30 days with baseline, in-hospital, and 30-day measures of renal function were retrospectively analyzed. Patients were stratified based on change in estimated glomerular filtration rate (eGFR) from baseline to 30 days as follows: improved (≥15% higher than baseline), worsened (≤15% lower), or unchanged (values in between). Univariable and multivariable models were constructed to identify predictors of subacute changes in renal function and of 2-year mortality. Of the 492 patients who met inclusion criteria, eGFR worsened in 102 (22%), improved in 110 (22%), and was unchanged in 280 (56%). AKI occurred in 90 patients (18%) and in only 27% of patients with worsened eGFR at 30 days. After statistical adjustment, worsened eGFR at 30 days (hazard ratio vs unchanged eGFR 2.09, 95% CI 1.37 to 3.19, p <0.001) was associated with worse survival, whereas improvement in renal function was not associated with survival (hazard ratio vs unchanged eGFR 1.30, 95% CI 0.79 to 2.11, p = 0.30). Worsened renal function at 30 days after TAVI is associated with increased mortality after TAVI. In conclusion, monitoring renal function after discharge may identify patients at high risk of adverse outcomes.

Association Between Angiotensin Receptor-Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Sacubitril/valsartan (S/V) treatment is associated with reverse cardiac remodeling and reductions in biomarkers reflecting ventricular wall stress and myocardial injury, such as NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT (high-sensitivity cardiac troponin T), and soluble suppressor of tumorigenicity 2 (sST2). How longitudinal changes in these biomarkers analyzed collectively are associated with cardiac remodeling in patients with heart failure with reduced ejection fraction treated with S/V is uncertain. METHODS: In a prospective study of S/V in patients with heart failure with reduced ejection fraction, this prespecified exploratory analysis included patients with serially collected biomarkers and echocardiographic measures of cardiac remodeling through 12 months of treatment. A multivariate latent growth curve model assessed associations between simultaneous changes in biomarkers and left ventricular ejection fraction and left atrial volume index. RESULTS: Seven hundred fifteen out of 794 total study participants were included (mean age 65 years, 73% male). Mean baseline left ventricular ejection fraction and left atrial volume index were 29% and 40 mL/m2, respectively. Adjusted geometric mean baseline concentrations for biomarkers included NT-proBNP of 649 pg/mL, hs-cTnT of 15.9 ng/L, and sST2 of 24.7 ng/mL. Following initiation of S/V, circulating concentrations of NT-proBNP, hs-cTnT, and sST2 significantly decreased within 30 days and remained significantly different than baseline at all subsequent timepoints. From baseline to month 12, decreases in adjusted biomarker concentrations averaged -27.9% (95% CI, -35.1% to -20.7%; P<0.001) for NT-proBNP; -6.7% (95% CI, -8.8% to -4.7%; P<0.001) for hs-cTnT; and -1.6% (95% CI, -2.9% to -0.4%; P<0.001) for sST2. NT-proBNP concentrations were predictive of later changes in hs-cTnT. The magnitude of reductions in NT-proBNP and hs-cTnT concentrations associated with improvements in left ventricular ejection fraction and left atrial volume index. There was no association between changes in sST2 and changes in other measures. CONCLUSIONS: Following initiation of S/V, NT-proBNP, hs-cTnT, and sST2 concentrations decreased significantly. Longitudinal changes in NT-proBNP and hs-cTnT together associated with left atrial and left ventricular reverse remodeling. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02887183.