Incident aortic stenosis in 49 449 men and 42 229 women investigated with routine echocardiography

Objective We addressed the paucity of data describing the characteristics and consequences of incident aortic stenosis (AS). Methods Adults undergoing echocardiography with a native aortic valve (AV) and no AS were studied. Subsequent age-specific and sex-specific incidence of AS were derived from echocardiograms conducted a median of 2.8 years apart. Progressive AV dysfunction and individually linked mortality were examined per AS category. Results 49 449 men (53.9%, 60.9±15.8 years) and 42 229 women (61.6±16.9 years) with no initial evidence of AS were identified. Subsequently, 6293 (6.9%) developed AS—comprising 5170 (5.6%), 636 (0.7%), 339 (0.4%) and 148 (0.2%) cases of mild, moderate, severe low-gradient and severe high-gradient AS, respectively. Age-adjusted incidence rates of all grades of AS were 17.5 cases per 1000 men/annum and 18.7 cases per 1000 women/annum: rising from ~5 to ~40 cases per 1000/annum in those aged 80 years. Median peak AV velocity increased by +0.57 (+0.36 to +0.80) m/s in mild AS compared with +2.75 (+2.40 to +3.19) m/s in severe high-gradient AS cases between first and last echocardiograms. During subsequent median 7.7 years follow-up, 24 577 of 91 678 cases (26.8%) died. Compared with no AS, the adjusted risk of all-cause mortality was 1.42-fold higher in mild AS, 1.92-fold higher in moderate AS, 1.95-fold higher in severe low-gradient AS and 2.27-fold higher in severe, high-gradient AS cases (all p<0.001). Conclusions New onset AS is a common finding among older patients followed up with echocardiography. Any grade of AS is associated with higher mortality, reinforcing the need for proactive vigilance

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Mild pulmonary hypertension and premature mortality among 154 956 men and women undergoing routine echocardiography

Although mild pulmonary hypertension (PHT) is known to be associated with increased mortality, its impact on premature mortality is largely unknown. We studied the distribution of estimated right ventricular systolic pressures (eRVSP) among 154 956 adults with no evidence of left heart disease investigated with echocardiography. We then examined individually linked mortality, premature mortality and associated life-years lost (LYL) according to eRVSP levels. The cohort comprised 70 826 men (61.3±17.7 years) and 84 130 women (61.4±18.4 years). Overall, 85 173 (55.0%), 49 276 (31.8%), 13 060 (8.4%) and 7447 (4.8%) cases had an eRVSP level indicative of no (\u3c30.0 mmHg), mild (30.0–39.9 mmHg), moderate (40.0–49.9 mmHg), or severe (≥50.0 mmHg) PHT, respectively. During median 5.7 (interquartile range 3.2–8.9) years follow-up, 38 456/154 986 (24.8%) individuals died. Compared to an eRVSP \u3c30.0 mmHg, age and sex-adjusted hazard ratios for all-cause and cardiovascular-related mortality were 1.90 (95% CI 1.84–1.96) and 1.85 (95% CI 1.74–1.97) respectively, for an eRVSP of 35.0–39.9 mmHg. Overall, 6,256 (54%) men and 7524 (55%) women died prematurely. As a proportion of all deaths, premature mortality rose from 46.7% to 79.2% among those with an eRVSP \u3c30.0 mmHg versus ≥60.0 mmHg with a mean of 5.1 to 11.4 LYL each time. However, due to more individuals affected overall, an eRVSP of 30.0–39.9 mmHg accounted for 58% and 53% of total LYL among men (40 606/70 019 LYL) and women (47 333/88 568 LYL), respectively. These data confirm that elevated eRVSP levels indicative of mild PHT are associated with increased risk of death. Moreover, this results in a substantive component of premature mortality/LYL that requires more proactive clinical surveillance and management

Diastolic dysfunction and mortality in 436 360 men and women: The National Echo Database Australia (NEDA)

Aims: To examine the characteristics/prognostic impact of diastolic dysfunction (DD) according to 2016 American Society of Echocardiography (ASE) and European Society of Cardiovascular Imaging (ESCVI) guidelines, and individual parameters of DD. Methods and results: Data were derived from a large multicentre mortality-linked echocardiographic registry comprising 436 360 adults with \u3e_1 diastolic function measurement linked to 100 597 deaths during 2.2 million person-years follow-up. ASE/ European Association of Cardiovascular Imaging (EACVI) algorithms could be applied in 392 009 (89.8%) cases; comprising 11.4% of cases with ‘reduced’ left ventricular ejection fraction (LVEF \u3c 50%) and 88.6% with ‘preserved’ LVEF (\u3e_50%). Diastolic function was indeterminate in 21.5% and 62.2% of ‘preserved’ and ‘reduced’ LVEF cases, respectively. Among preserved LVEF cases, the risk of adjusted 5-year cardiovascular-related mortality was elevated in both DD [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.22–1.42; P \u3c 0.001] and indeterminate status cases (OR 1.11, 95% CI 1.04–1.18; P \u3c 0.001) vs. no DD. Among impaired LVEF cases, the equivalent risk of cardiovascular-related mortality was 1.51 (95% CI 1.15–1.98, P \u3c 0.001) for increased filling pressure vs. 1.25 (95% CI 0.96–1.64, P = 0.06) for indeterminate status. Mitral E velocity, septal e’ velocity, E:e’ ratio, and LAVi all correlated with mortality. On adjusted basis, pivot-points of increased risk for cardiovascular-related mortality occurred at 90 cm/s for E wave velocity, 9 cm/s for septal e’ velocity, an E:e’ ratio of 9, and an LAVi of 32 mL/m2 . Conclusion: ASE/EACVI-classified DD is correlated with increased mortality. However, many cases remain ‘indeterminate’. Importantly, when analysed individually, mitral E velocity, septal e’ velocity, E:e’ ratio, and LAVi revealed clear pivotpoints of increased risk of cardiovascular-related mortality

Change in ejection fraction and long-term mortality in adults referred for echocardiography

Aims We investigated long-term mortality associated with changes in left ventricular ejection fraction (LVEF) in a large, real-world patient cohort. Methods and results A total of 117 275 adults (63 ± 16 years, 46% women) had LVEF quantified by the same method ≥6 months apart. This included 17 343 cases (66 ± 15 years, 48% women) being initially investigated for heart failure (HF). During 3.3 [interquartile range (IQR) 1.7–6.0] years from first to last echocardiogram, median change in LVEF was −1 (IQR −8 to +5) units from a baseline of 62% (IQR 54–69%). During subsequent 7.6 (IQR 4.3–10.1) years of follow-up, 11 397 (9.7%) and 34 101 (29.1%) cases died from cardiovascular disease and all causes, respectively. Actual 5-year, all-cause mortality increased from 12% to 29% among those with the smallest to the largest decrease in LVEF (from 30 units); the adjusted risk of cardiovascular-related mortality increased two- to eightfold beyond a >10-unit decline in LVEF (vs. minimal change; P 30-unit increase to >30-unit decline in LVEF (vs. minimal change; P < 0.001 for both comparisons). A distinctive, bi-directional plateau of improved vs. worsening mortality was evident around a final LVEF of 50% to 55%. Conclusions These data, derived from a large, heterogeneous cohort of adults being followed up with echocardiography, suggest that modest LVEF changes (particularly around an LVEF of 50–55%) may be of clinical significance

Change in ejection fraction and long‐term

Aims We investigated long-term mortality associated with changes in left ventricular ejection fraction (LVEF) in a large, real-world patient cohort. Methods and results A total of 117 275 adults (63 ± 16 years, 46% women) had LVEF quantified by the same method ≥6 months apart. This included 17 343 cases (66 ± 15 years, 48% women) being initially investigated for heart failure (HF). During 3.3 [interquartile range (IQR) 1.7–6.0] years from first to last echocardiogram, median change in LVEF was −1 (IQR −8 to +5) units from a baseline of 62% (IQR 54–69%). During subsequent 7.6 (IQR 4.3–10.1) years of follow-up, 11 397 (9.7%) and 34 101 (29.1%) cases died from cardiovascular disease and all causes, respectively. Actual 5-year, all-cause mortality increased from 12% to 29% among those with the smallest to the largest decrease in LVEF (from 30 units); the adjusted risk of cardiovascular-related mortality increased two- to eightfold beyond a >10-unit decline in LVEF (vs. minimal change; P 30-unit increase to >30-unit decline in LVEF (vs. minimal change; P < 0.001 for both comparisons). A distinctive, bi-directional plateau of improved vs. worsening mortality was evident around a final LVEF of 50% to 55%. Conclusions These data, derived from a large, heterogeneous cohort of adults being followed up with echocardiography, suggest that modest LVEF changes (particularly around an LVEF of 50–55%) may be of clinical significance