Clinical Investigation
Aortic Stenosis
Risk for Mortality with Increasingly Severe Aortic Stenosis: An International Cohort Study

https://doi.org/10.1016/j.echo.2022.09.020Get rights and content

Highlights

  • The authors evaluated risk for progressive AS in two large parallel cohorts.

  • Risk for mortality in patients with AS is linear but plateaus above 3.0 m/sec.

  • These data support ongoing clinical trials in patients with moderate AS.

Background

Aortic stenosis (AS) is the most common valvular heart disease in high-income countries. Adjusted for clinical confounders, the risk associated with increasing AS severity across the spectrum of AS severity remains uncertain.

Methods

The authors conducted an international, multicenter, parallel-cohort study of 217,599 Australian (mean age, 76.0 ± 7.3 years; 49.3% women) and 30,865 US (mean age, 77.4 ± 7.3 years; 52.2% women) patients aged ≥65 years who underwent echocardiography. Patients with previous aortic valve replacement were excluded. The risk of increasing AS severity, quantified by peak aortic velocity (Vmax), was assessed through linkage to 97,576 and 14,481 all-cause deaths in Australia and the United States, respectively.

Results

The distribution of AS severity (mean Vmax, 1.7 ± 0.7 m/sec) was similar in both cohorts. Compared with those with Vmax of 1.0 to 1.49 m/sec, those with Vmax of 2.50 to 2.99 m/sec (US cohort) or Vmax of 3.0 to 3.49 m/sec (Australian cohort) had a 1.5-fold increase in mortality risk within 10 years, adjusting for age, sex, presence of left heart disease, and left ventricular ejection fraction. Overall, the adjusted risk for mortality plateaued (1.75- to 2.25-fold increased risk) above a Vmax of 3.5 m/sec. This pattern of mortality persisted despite adjustment for a comprehensive list of comorbidities and treatments within the US cohort.

Conclusions

Within large, parallel patient cohorts managed in different health systems, similar patterns of mortality linked to increasingly severe AS were observed. These findings support ongoing clinical trials of aortic valve replacement in patients with nonsevere AS and suggest the need to develop and apply more proactive surveillance strategies in this high-risk population.

Section snippets

Study Design

We conducted a multicenter, international, parallel-group, observational cohort study with individually linked long-term follow-up outcomes data, adhering to the Reporting of Studies Conducted Using Observational Routinely Collected Health Data statement for the conduct and reporting of observational studies.19 Two matching real-world, clinical cohorts comprising patients undergoing routine echocardiography were studied, National Echo Database Australia and the Medicare-linked Electronic

Study Cohorts

As shown in Figure 1, individually linked mortality data were available for 211,635 Australian and 30,810 US patients aged ≥65 years with Vmax levels determined by echocardiography. A total of 1,081 US individuals (1.6%) and 18,405 Australian individuals (2.9%) were excluded from the analysis because of prior AVR. Of those not excluded on the basis of AVR at baseline, a total of 393 individuals (0.9%) in the US cohort and 5,454 (1.1%) in the Australian cohort underwent AVR during follow-up (of

Discussion

In a combined analysis of nearly 250,000 patients from two different continents (and health systems), we found a consistent pattern of increased risk for mortality associated with increasing peak aortic valve velocity, indicative of progressively worsening AS. Specifically, we found that after adjusting for potentially important clinical confounders and contributors to excess mortality, an inflection point for increased mortality in patients presenting with less severe forms of AS (compared

Conclusion

In a large, parallel-group, international cohort study, we observed a consistent pattern of increasing mortality associated with increasing AS severity. The risk for mortality linearly increased above a Vmax of 2.0 to 3.0 m/sec and plateaued above a Vmax of 3.0 m/sec. This pattern persisted despite detailed adjustment for clinical comorbidities, including coronary artery disease, cancer, and dementia, pharmacologic treatments, and prior revascularization. Overall, these findings support ongoing

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  • This study was supported by an investigator-initiated grant from Edwards Lifesciences (with no input or influence on the interpretation of study data or this report). Dr. Strom additionally reports support from the National, Heart, Lung, and Blood Institute (grant 1K23HL144907).

    Dr. Stewart is supported by the National Health and Medical Research Council of Australia (grant GNT1135894). Dr. Strom is supported by grants from the National Heart, Lung, and Blood Institute (grant 1K23HL144907), Anumana, HeartSciences, and Ultromics. Drs. Strange and Playford are the co–principal investigators and directors of National Echo Database Australia (a not-for-profit research entity), which has received investigator-initiated funding support from Novartis Pharmaceuticals and Edward Lifesciences in the past 3 years. Dr. Stewart has received consultancy fees from National Echo Database Australia. Drs. Stewart, Playford, and Strange have previously received consultancy and speaking fees from Edwards Lifesciences. Dr. Strom is a member of the scientific advisory board for Edwards Lifesciences, is a consultant for Bracco Diagnostics and General Electric Healthcare, and has received speaker fees from Northwest Imaging Forums, unrelated to the submitted work.

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