Patients with moderate aortic stenosis (AS) may have a higher mortality risk than those with no or mild AS but a lower risk than patients with severe AS, according to a new meta-analysis. AS is the most common valvular heart disease in the Western Hemisphere – affecting approximately 5% of individuals over 65 years of age, noted the study authors, led by Augustin Coisne, MD, PhD, from the Cardiovascular Research Foundation; Albert Einstein College of Medicine, New York; and the University of Lille, France. “Although the impact of severe AS on clinical outcomes has been extensively reported in the literature, conflicting data exist about the clinical course of patients with lower grades of stenosis,” said the authors, writing in a study published online Monday and in the Aug. 22 issue of JACC: Cardiovascular Interventions. “Given the growing interest in intervention in moderate AS patients, a deeper understanding of the population risk profile and clinical course of the disease may serve as a benchmark for future clinical studies.” Study setup Coisne and colleagues performed a comprehensive meta-analysis to evaluate the long-term clinical outcomes of patients with moderate AS and compared them with other stages of the disease. Studies were included if they included adult patients with moderate AS quantified by echocardiography or heart catheterization and at least the event of death during follow-up and the mean or median duration of follow-up were reported, they noted. The primary endpoint was all-cause death, while secondary endpoints were cardiac death, heart failure, sudden death and aortic valve replacement. A total of 25 observational studies met eligibility criteria for the initial meta-analysis of outcomes for patients with moderate AS. Within the data set, the average patient age was 74 years (95% confidence interval [CI]: 72 to 76), while 41% were women (95% CI: 32% to 52%) and pooled mean left ventricular ejection fraction (LVEF) was within normal limits (58% [95% CI: 55% to 61%]). Further meta-analysis comparing the all-cause mortality of patients with no or mild versus moderate AS pooled data from 277,041 patients in eight studies with a mean follow-up of 3.7 years, while an analysis comparing the all-cause mortality of patients with severe versus moderate AS pooled data from 13,848 patients from 11 studies with a mean follow-up of 3.8 years. “For the meta-analysis comparing AS grades, we chose to include only the studies reporting separate outcomes for patients with moderate and other stages of AS and exclude those including patients with only 1 grade of AS,” noted Coisne and colleagues. “Given that the observed mortality in patients with mild AS was found to be indistinguishable from the expected mortality of the general population, we chose to pool patients with no and mild AS,” they added. Key findings The team reported that pooled rates per 100 person-years were 9.0 (95% CI: 6.9 to 11.7) for all-cause death, 4.9 (95% CI: 3.1 to 7.5) for cardiac death, 3.9 (95% CI: 1.9 to 8.2) for heart failure, 1.1 (95% CI: 0.8 to 1.5) for sudden death, and 7.2 (95% CI: 4.3 to 12.2) for aortic valve replacement. Furthermore, meta-regression analyses detected that diabetes (P = 0.019), coronary artery disease (P = 0.017), presence of symptoms (P < 0.001), and left ventricular (LV) dysfunction (P = 0.009) were associated with a significant impact on the overall estimate of all-cause death for patients with moderate AS. Indeed, all-cause mortality was higher in patients with reduced LV ejection fraction of <50% (16.5 per 100 person-years [95% CI: 5.2 to 52.3]) than with normal LV ejection fraction (4.2 per 100 person-years [95% CI: 1.4 to 12.8]). Compared with moderate AS, the incidence rate difference of all-cause mortality was -3.9 (95% CI: -6.7 to -1.1) for no or mild AS and +2.2 (95% CI: +0.8 to +3.5) for severe AS patients, said Coisne and colleagues. “Moderate AS appears to be associated with a mortality risk higher than no or mild AS but lower than severe AS, which increases in specific population subsets,” they noted, adding that the impact of early intervention in moderate AS patients having high-risk features “deserves further investigation.” Not a benign condition Writing in an accompanying editorial, Craig R. Narins, MD, from the University of Rochester, New York, said the findings of the new meta-analysis “support the contention that moderate aortic stenosis is not a benign condition.” “The current study effectively assimilates a wealth of data, and raises some intriguing issues,” said Narins. “As reports have accrued supporting an association between moderate aortic stenosis, cardiac damage, and adverse clinical outcomes including all-cause mortality, interest has turned toward the question of whether individuals with moderate aortic stenosis, or certain subsets thereof, might derive value from transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement,” he noted, adding that the benefits vs risks of valve replacement earlier in the progression of aortic stenosis demands special attention. Indeed, the editorialist noted that the “traditional, but possibly overly simplistic, approach” of using a set binary hemodynamic cut-point to trigger valve replacement has come under scrutiny – adding that trial results examining the role of TAVR in moderate aortic stenosis are “eagerly anticipated.” “It is highly conceivable that different patient subsets may benefit from aortic valve replacement at various points along the disease spectrum, possibly in relation to clinical comorbidities, results of cardiac imaging studies, exercise stress testing, or yet to be determined parameters,” he said. “As in many other areas involving patient care, moving from a ‘1 size fits all’ approach toward an individualized ‘precision medicine’ approach makes sense and is imaginably the future of therapy for aortic valve disease.” Sources: Coisne A, Scotti A, Latib A, et al. Impact of Moderate Aortic Stenosis on Long-Term Clinical Outcomes: A Systematic Review and Meta-Analysis. JACC Cardiovasc Interv 2022;15:1664-674. Narins CR. Implications of Moderate Aortic Stenosis. JACC Cardiovasc Interv 2022;15:1675-1677. Image Credit: Pitchy – stock.adobe.com