Editor's Note: This Expert Analysis is part of a series presenting perspectives on major ESC Congress 2019 trials. Please follow this link for the companion articles.

Aortic stenosis (AS) is the most common valvular disorder in Europe and North America. The risk for mortality in patients with severe symptomatic AS has been clearly established, but the morbidity and mortality with moderate AS and the risk versus benefit of treating moderate AS with aortic valve replacement remain controversial. Current American College of Cardiology/American Heart Association and European Society of Cardiology/ European Association for Cardio-Thoracic Surgery guidelines recommend that surgical intervention for moderate AS be considered only when the patient is undergoing cardiac surgery for another indication.^1,2 In a previous natural history study of 305 patients with moderate AS and left ventricular systolic dysfunction across 4 academic centers from North America and Europe, the authors reported a 61% incidence of all-cause death, heart failure (HF) hospitalization, and aortic valve replacement at 4 years of follow-up.³ Another study focused on patients with moderate AS and preserved left ventricular function and reported poorer survival in these patients compared with the general population.⁴

The current study attempts to address an important gap in literature by comparing patients with moderate AS with those with different grades of AS as well as those without AS.⁵ The authors use data from the National Echocardiography Database Australia, which was linked with Australia's National Death Index, to assess survival. Out of a total of 241,303 patients with measured aortic valve hemodynamics, 25,827 patients had some degree of AS, and 3,315 had moderate AS. The median follow-up for this study was 1,208 days.

As expected, increasing severity of AS was found to be associated with poorer 1-year and 5-year mortality. It is interesting to note that using no AS as a reference, the 5-year mortality from moderate AS (56%; odds ratio [OR] 2.6; 95% confidence interval [CI], 2.31-2.92) was significant and very similar to the 5-year mortality from severe AS (67%; OR 3.05; 95% CI, 2.79-3.33). This trend was even more pronounced in patients without concurrent left heart disease. When studying overall survival using age- and gender-adjusted Cox regression models, there was a clearer dichotomy of risk, with no AS (reference) and mild AS (hazard ratio [HR] 1.02; 95% CI, 0.98-1.07; p = 0.32) having similar risk profiles and moderate AS (HR 1.19; 95% CI, 1.12 -1.26; p < 0.001) and severe AS (HR 1.22; 95% CI, 1.13-1.31; p < 0.001) having similar risk profiles. The authors also determined that an increased risk of long-term mortality and cardiovascular-disease-related mortality was evident at a mean aortic valve gradient of 20 mmHg and peak aortic valve velocity of 3 m/s.

The findings of this provocative study suggest that moderate AS may not be as benign as previously presumed. These patients are high risk, and it is important to monitor them closely. It is essential to recognize, however, that degenerative AS does not occur in isolation. Patients with moderate AS have co-existent hypertension, diabetes, coronary artery disease, atrial fibrillation, HF, renal failure, and other conditions that may all contribute significantly to mortality.⁴ It is possible that part of the excess mortality seen with moderate AS in the current study may be attributable to these comorbidities rather than AS. The lack of granular clinical data (and inability to adjust for these data) is a major limitation of the current study. Regardless, this investigation lays the foundation for future research on the prognostic implications and treatment for moderate AS. As the horizon of transcatheter aortic valve replacement expands, it addresses an unmet need for aortic valve replacement in patients who may not be candidates for surgical aortic valve replacement. Whether patients with moderate AS will benefit from aortic valve replacement (surgical or transcatheter) remains to be seen. We eagerly await the results of the randomized TAVR UNLOAD (Transcatheter Aortic Valve Replacement to Unload the Left Ventricle in Patients With Advanced Heart Failure) study, which will test the hypothesis that transcatheter aortic valve replacement in addition to optimal HF therapy improves clinical outcomes in patients with moderate AS and HF with reduced ejection fraction.

References

1. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2438-88.
2. Baumgartner H, Falk V, Bax JJ, et al. 2017 ESC/EACTS Guidelines for the Management of Valvular Heart Disease. Rev Esp Cardiol (Engl Ed) 2018;71:110.
3. van Gils L, Clavel MA, Vollema EM, et al. Prognostic Implications of Moderate Aortic Stenosis in Patients With Left Ventricular Systolic Dysfunction. J Am Coll Cardiol 2017;69:2383-92.
4. Delesalle G, Bohbot Y, Rusinaru D, Delpierre Q, Maréchaux S, Tribouilloy C. Characteristics and Prognosis of Patients With Moderate Aortic Stenosis and Preserved Left Ventricular Ejection Fraction. J Am Heart Assoc 2019;8:e011036.
5. Strange G, Stewart S, Celermajer D, et al. Poor Long-Term Survival in Patients With Moderate Aortic Stenosis. J Am Coll Cardiol 2019;74:1851-63.

Keywords: ESC Congress, esc 2019, ESC 19, Cardiac Surgical Procedures, Adrenergic beta-Antagonists, Acute Coronary Syndrome, American Heart Association, Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Antagonists, Aortic Valve, Aortic Valve Stenosis, Aspirin, Atrial Fibrillation, Australia, Cohort Studies, Cardiac Rehabilitation, Comorbidity, Confidence Intervals, Coronary Artery Bypass, Coronary Artery Disease, Diabetes Mellitus, Dilatation, Dyslipidemias, Drug Prescriptions, Echocardiography, Electronic Health Records, Diet, Follow-Up Studies, Heart Failure, Heart Diseases, Heart Valve Prosthesis, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Heart Ventricles, Hospitalization, Hypertension, Hypotension, Incidence, Life Style, Long-Term Care, Mitral Valve, Mitral Valve Insufficiency, Myocardial Infarction, Nutritionists, Odds Ratio, Office Visits, Outcome Assessment, Health Care, Papillary Muscles, Percutaneous Coronary Intervention, Pharmacists, Physical Therapists, Physicians, Primary Care, Platelet Aggregation Inhibitors, Primary Health Care, Prospective Studies, Pulmonary Circulation, Referral and Consultation, Prognosis, Registries, Renal Insufficiency, Research, Renin-Angiotensin System, Risk, Secondary Prevention, Sleep Apnea Syndromes, Stroke, Stroke Volume, Smoking Cessation, Surgeons, Systole, Taxus, Thoracic Surgery, Transcatheter Aortic Valve Replacement, Ventricular Dysfunction, Ticlopidine, Ventricular Function, Left

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