The lack of an association between RHR and AVR is potentially due to competing risks, as higher RHRs may be more common in sicker patients who are more likely to die or be deemed unsuitable for major surgery. The study was limited by the inherent shortcomings of interpreting big data and, in particular, the lack of comprehensive clinical profiling. This is the largest study examining the association between RHR and the development and haemodynamic progression of AS, and the first to show that it is significantly associated with both. AS: aortic stenosis AVR: aortic valve replacement bpm: beats per minute CI: confidence interval CVD: cardiovascular death HR: hazard ratio N: sample size. ![]() Multivariable association between RHR (10bpm increase) and study endpoints. RHR was independently associated with rate of change of each measurement index of AS severity, including Vmax (0.01 m/s per year/10 bpm P < 0.001), MPG (0.05 mmHg per year/10 bpm P < 0.001), and AVA (0.01 cm 2 per year/10 bpm P < 0.001). ![]() There was no evidence of a significant association between RHR and receipt of an AVR (HR/10 bpm, 0.97 95% CI 0.94–1.00 P = 0.057), reached by 1869 patients. The composite event rate was significantly higher in patients with an RHR ≥ 70 bpm compared with those with an RHR < 70 bpm (log-rank P-value< 0.001, Supplementary Figure). RHR was independently associated with the primary endpoint and the secondary endpoints of cardiovascular death (HR/10 bpm, 1.04 95% CI 1.02–1.06 P < 0.001), reached by 5843 patients, and the composite endpoint of developing severe AS, cardiovascular death, or AVR (HR/10 bpm, 1.03 95% CI 1.02–1.05 P < 0.001), reached by 7434 patients ( Figure 1). The initial study cohort comprised 55585 individuals: 54% male, mean age 63 years, and median baseline RHR 73 bpm, with 847 patients reaching the primary endpoint. The relationship between RHR and annualized AS progression rate, defined as the change in standard indices of AS severity, was analysed using multivariable regression models. Multivariable Cox proportional hazards regression models were used to examine the association between RHR and all time-to-event outcomes (primary endpoint of development of severe AS, secondary endpoints of cardiovascular death, receipt of an AVR, and a composite of these). We excluded those with severe AS (high or low gradient), AVR, or congenital bicuspid aortic valve at baseline. We performed a retrospective cohort study and included only patients with baseline RHR and haemodynamic assessment of the aortic valve on at least two echocardiograms, separated by at least 6 months, available. ![]() NEDA is registered with the Australia New Zealand Clinical Trials Registry (ACTRN12617001387314), and ethical approval has been obtained from all relevant Human Research Ethics Committees.Īt study census (May 2019), NEDA included more than 1 million echocardiography reports from 631824 individuals (≥18 years). 5 Individual NEDA data have been linked to the Australian National Death Index, and the cause of death has been categorized according to the International Classification of Diseases, Tenth Revision coding system (ICD-10). We used the National Echocardiography Database of Australia (NEDA), an observational registry, which collects individual echocardiographic data, combined with basic demographic profiling, on a retrospective and prospective basis from participating centres throughout Australia. We hypothesized that elevated RHR is independently associated with the development and accelerated haemodynamic progression of AS. 2–4 Aortic valve calcification is the most common precursor to AS and is associated with faster disease progression. Furthermore, increased RHR predicts accelerated calcification in coronary artery disease and carotid stenosis, and increased incidence and progression of aortic valve calcification in patients with and without a confirmed diagnosis of AS. Therefore, there is a clear need for novel therapeutic interventions to slow or prevent the progression of AS and reduce associated adverse outcomes.Ī high resting heart rate (RHR) is a risk factor for cardiovascular disease, adverse cardiac events, and cardiovascular mortality. 1 AVR confers procedural risk and has limited availability. Severe AS is associated with a dismal prognosis without timely intervention, and aortic valve replacement (AVR), either surgically or via a trans-catheter approach, is the only treatment. Aortic stenosis (AS) affects ∼2% of individuals aged over 65 years in high-income countries, and the prevalence is projected to double by 2050.
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