BACKGROUND: Guidelines acknowledge that discordant low-gradient (LG) aortic stenosis (AS) may be severe, but verifying this can be challenging. Right heart catheterization during exercise is considered the gold standard for evaluating ventricular hemodynamics. No invasive studies have compared the hemodynamic response of discordant LG and severe AS during exercise. The aim of this observational study was to describe exercise hemodynamics in patients with asymptomatic discordant AS and left ventricular ejection fraction ≥50%. METHODS: Patients with aortic valve area ≤1.5 cm 2 underwent right heart catheterization at rest and during maximal exercise, measuring pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and the PCWP/CO-slope. Patients were stratified into 3 groups: discordant LG AS (aortic valve area ≤1.0 cm 2 and mean gradient <40 mm Hg); moderate AS (aortic valve area >1.0 cm 2 ); and high-gradient (HG) severe AS (aortic valve area ≤1.0 cm 2 and mean gradient ≥40 mm Hg). RESULTS: Among 86 patients, 17 (20%) had discordant LG, 49 (57%) moderate, and 20 (23%) HG severe AS. The median PCWP/CO-slope was significantly steeper in discordant LG (3.3 [interquartile range, 2.1–4.3] mm Hg/L/min) and HG severe AS (2.7 [1.9–3.4] mm Hg/L per minute) compared with moderate AS (1.9 [0.7–2.8] mm Hg/L per minute), P =0.004. In a regression model adjusted for age, sex, and rest PCWP, systemic arterial compliance and AS severity were significantly associated with the PCWP/CO-slope. Furthermore, patients with discordant LG AS had a leftward-upward shift in the PCWP/CO-curve. CONCLUSIONS: Discordant LG and HG severe AS had similar hemodynamic responses to exercise with steeper PCWP/CO-slope than in moderate AS, suggesting that discordant LG AS is a severe form of AS. In addition, the left upwards shift in PCWP/CO-curve for discordant LG compared with HG severe AS indicates that this group also has heart failure with preserved ejection fraction physiology. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04913870 and NCT02395107.
Acute Valve Syndrome Before Aortic Valve Replacement: Impact on Clinical Outcomes, Health Care Costs, and Resource Use
Background A classification system describing clinical presentation before aortic valve replacement (AVR) has recently been proposed (stable valve syndrome [SVS]), mildly symptomatic (progressive valve syndrome), or with acute and severe signs and symptoms (acute valve syndrome [AVS]). We aimed to evaluate the clinical impact, health care costs, and resource use associated with the mode of clinical presentation at the time of AVR among patients presenting with aortic stenosis. Methods Using the Market Clarity database (2017–2023), patients >18 years old with aortic stenosis and undergoing AVR (transcatheter or surgical) were included. Patients were categorized as SVS, progressive valve syndrome, or AVS based on their clinical presentation during the 1 year before AVR. All‐cause death, heart failure hospitalization, total health care costs (index hospitalization plus 1‐year follow‐up), and resource use were compared across clinical presentation groups using adjusted regression models. Results Of the 24 075 patients undergoing AVR for aortic stenosis, 270 (1.1%) had SVS, 10 195 (42.3%) progressive valve syndrome, and 13 610 (56.5%) AVS. Compared with SVS, AVS presentation was associated with increased risk of 1‐year death (adjusted hazard ratio [aHR], 2.93 [95% CI, 1.1–7.8]; P =0.03) and heart failure hospitalization (aHR, 4.15 [95% CI, 1.6–11.1]; P <0.01) after AVR. The total costs of AVR and 1‐year follow‐up were significantly higher in both the progressive valve syndrome (difference $27 410 [$13 507–$41 314]) and AVS groups (difference $36 267 [$22 302–$50 232]) compared with patients with SVS. Conclusions AVS was frequent among patients undergoing AVR and was associated with increase in death, heart failure hospitalization, health care costs, and resource use 1 year after AVR, and SVS presentation was associated with the best clinical and economic outcomes.
Abstract Aims This study aims to describe the prevalence of discordant mild/moderate aortic stenosis (AS) in a population-based study and to identify the mechanisms that lead to reduced stroke volume (SV) and discordant moderate AS. Methods and results Discordant high-gradient (HG)-mild AS, defined as AVA > 1.5 cm2 and mean pressure gradient (MG) of 20–40 mmHg, and discordant low-gradient (LG) moderate AS, defined as AVA 1.0–1.5 cm2 and MG < 20 mmHg, were assessed in 883 individuals from the DANCAVAS screening study with aortic valve calcification and 257 individuals form the PROGRESSA study excluding those with left ventricular (LV) ejection fraction < 50%. In the DANCAVAS cohort, 150 men had mild/moderate AS of which 34% had discordance between MG and AVA, representing 66% with moderate AS. Among 262 patients in the combined cohort, 39% had discordant LG-moderate AS and 6% discordant HG-mild AS. Compared with concordant mild and moderate AS, individuals with discordant LG-moderate AS were more likely to present with LV concentric remodelling geometry (26 vs. 33 vs. 45%, P < 0.001), increased valvulo-arterial impedance (3.3 ± 0.7 vs. 3.6 ± 0.5 vs. 4.1 ± 0.7 mmHg/mL/m2, P < 0.001), and reduced systemic arterial compliance (SAC) (0.74 ± 0.22 vs. 0.81 ± 0.22 vs. 0.64 ± 0.18 mL/m2/mmHg, P < 0.001). Factors associated with SV index were relative wall thickness, LV end-diastolic diameter index, SAC, and LV remodelling pattern. Conclusion Discordant moderate AS is common, accounting for two-thirds of patients with moderate AS in the general male population. Patients with discordant LG-moderate AS have predominantly a concentric remodelling pattern with reduced SV. Reduced SV index was associated with signs of reduced vascular compliance, suggesting that altered vascular properties drive differences in remodelling patterns and discordant moderate AS.
One-Year Outcomes of Transseptal Mitral Valve-in-Valve in Intermediate Surgical Risk Patients
BACKGROUND: Transcatheter mitral valve-in-valve replacement offers a less-invasive alternative for high-risk patients with bioprosthetic valve failure. Limited experience exists in intermediate-risk patients. We aim to evaluate 1-year outcomes of the PARTNER 3 mitral valve-in-valve study. METHODS: This prospective, single-arm, multicenter study enrolled symptomatic patients with a failing mitral bioprosthesis demonstrating greater than or equal to moderate stenosis and regurgitation and Society of Thoracic Surgeons score ≥3% and <8%. A balloon-expandable transcatheter heart valve (SAPIEN 3, Edwards Lifesciences) was used via a transeptal approach. The primary end point was the composite of all-cause mortality and stroke at 1 year. RESULTS: A total of 50 patients from 12 sites underwent mitral valve-in-valve from 2018 to 2021. The mean age was 70.1±9.7 years, mean Society of Thoracic Surgeons score was 4.1%±1.6%, and 54% were female. There were no primary end point events (mortality or stroke) through 1 year, and no left-ventricular outflow tract obstruction, endocarditis, or mitral valve reintervention was reported. Six patients (12%) required rehospitalization, including heart failure (n=2), minor procedural side effects (n=2), and valve thrombosis (n=2; both resolved with anticoagulation). An additional valve thrombosis was associated with no significant clinical sequelae. From baseline to 1 year, all subjects with available data had none/trace or mild (grade 1+) mitral regurgitation and the New York Heart Association class improved in 87.2% (41/47) of patients. CONCLUSIONS: Mitral valve-in-valve with a balloon-expandable valve via transseptal approach in intermediate-risk patients was associated with improved symptoms and quality of life, adequate transcatheter valve performance, and no mortality or stroke at 1-year follow-up. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03193801.
Moderate Aortic Valve Stenosis Is Associated With Increased Mortality Rate and Lifetime Loss: Systematic Review and Meta‐Analysis of Reconstructed Time‐to‐Event Data of 409 680 Patients
Background The mortality risk attributable to moderate aortic stenosis (AS) remains incompletely characterized and has historically been underestimated. We aim to evaluate the association between moderate AS and all‐cause death, comparing it with no/mild AS (in a general referral population and in patients with heart failure with reduced ejection fraction). Methods and Results A systematic review and pooled meta‐analysis of Kaplan–Meier‐derived reconstructed time‐to‐event data of studies published by June 2023 was conducted to evaluate survival outcomes among patients with moderate AS in comparison with individuals with no/mild AS. Ten studies were included, encompassing a total of 409 680 patients (11 527 with moderate AS and 398 153 with no/mild AS). In the overall population, the 15‐year overall survival rate was 23.3% (95% CI, 19.1%–28.3%) in patients with moderate AS and 58.9% (95% CI, 58.1%–59.7%) in patients with no/mild aortic stenosis (hazard ratio [HR], 2.55 [95% CI, 2.46–2.64]; P <0.001). In patients with heart failure with reduced ejection fraction, the 10‐year overall survival rate was 15.5% (95% CI, 10.0%–24.0%) in patients with moderate AS and 37.3% (95% CI, 36.2%–38.5%) in patients with no/mild AS (HR, 1.83 [95% CI, 1.69–2.0]; P <0.001). In both populations (overall and heart failure with reduced ejection fraction), these differences correspond to significant lifetime loss associated with moderate AS during follow‐up (4.4 years, P <0.001; and 1.9 years, P <0.001, respectively). A consistent pattern of elevated mortality rate associated with moderate AS in sensitivity analyses of matched studies was observed. Conclusions Moderate AS was associated with higher risk of death and lifetime loss compared with patients with no/mild AS.
Computed tomography calcium scoring in aortic stenosis: bicuspid versus tricuspid morphology
Objective CT aortic valve calcium score (AVCscore) and density (AVCdensity) thresholds have been recommended for aortic stenosis (AS) severity assessment in tricuspid aortic valve (TAV). We aimed to compare AVCscore and AVCdensity in bicuspid aortic valve (BAV) versus TAV. Methods Retrospective single-centre study of patients with echocardiographic AS-severity and CT-AVC assessments within 6 months, and left ventricular ejection fraction ≥50%, all referred for clinical AS evaluation. Severe AS was defined as aortic valve area (AVA) ≤1 cm2 or indexed AVA ≤0.6cm2/m2 plus mean gradient ≥40 mm Hg or peak velocity ≥4 m/s. AVC was assessed by Agatston method. Results Of the 1957 patients, 328 had BAV and 1629 had TAV, age 65±11 vs 80±9 years (p<0.001), men 65% vs 56% (p=0.006), respectively. BAV morphology was associated with higher AVCscore and AVCdensity independent of age, comorbidities and AS severity (p<0.001) in men only (sex and BAV interaction p<0.001). In patients with severe AS, mean AVCscore and AVCdensity were higher in BAV-men than that in TAV-men (both p<0.001), but similar in BAV-women and TAV-women (both p≥0.4). Such patterns remained the same after adjustment for clinical covariates and AS severity. Best thresholds for severe AS diagnosis in BAV-men were 2916 AU by AVCscore and 600 AU/cm2 by AVCdensity which were higher than the guideline-recommended thresholds, while thresholds in BAV-women (1036 AU and 282 AU/cm2) were similar to guideline-recommended ones. Conclusion Valve calcification in AS differs according to valve morphology and sex. BAV-men with severe AS exhibit greater AVCscore and AVCdensity than TAV-men. This presents a diagnostic challenge to the current guidelines, which needs confirmation in larger studies.
Outcomes From Transcatheter Aortic Valve Replacement in Patients With Low-Flow, Low-Gradient Aortic Stenosis and Left Ventricular Ejection Fraction Less Than 30%
Bioprostheses are prone to structural valve degeneration, resulting in limited long-term durability. A significant challenge when comparing the durability of different types of bioprostheses is the lack of a standardized terminology for the definition of a degenerated valve. This issue becomes especially important when we try to compare the degeneration rate of surgically inserted and transcatheter bioprosthetic valves. This document, by the VIVID (Valve-in-Valve International Data), proposes practical and standardized definitions of valve degeneration and provides recommendations for the timing of clinical and imaging follow-up assessments accordingly. Its goal is to improve the quality of research and clinical care for patients with deteriorated bioprostheses by providing objective and strict criteria that can be utilized in future clinical trials. We hope that the adoption of these criteria by both the cardiological and surgical communities will lead to improved comparability and interpretation of durability analyses.
Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis