Prognostic Value of E/E′ Ratio in Patients With Unoperated Severe Aortic Stenosis

ObjectivesThe aim of this study was to evaluate the value of clinical and echo-Doppler parameters for the prognosis of unoperated severe aortic stenosis (AS).BackgroundApproximately one-third of severe, symptomatic AS patients are denied surgery. Risk stratification of unoperated AS is important to determine eligibility for percutaneous aortic valve replacement, an evolving treatment option for AS patients deemed suboptimal for surgical aortic valve replacement.MethodsWe retrospectively compared clinical and echo-Doppler parameters between survivors and nonsurvivors of 125 patients with unoperated severe AS.ResultsThe 1-year survival rate was 62.4%. In univariate analysis, survivors compared with nonsurvivors were younger (80.0 ± 10.9 years vs. 84.9 ± 11.1 years, p = 0.02), had a greater left ventricular ejection fraction (LVEF) (55 ± 15% vs. 50 ± 16%, p = 0.042), a higher left ventricular stroke volume (63 ± 19 ml vs. 56 ± 13 ml, p = 0.015), a lower E/E′ ratio (12.19 ± 5.7 vs. 16.87 ± 7.43, p < 0.001), and a lower prevalence of E/E′ >15 (20% vs. 55%, p < 0.001). Symptomatic status was nonsignificantly different between survivors and nonsurvivors. In patients with an LVEF ≥50%, the subgroup with E/E′ ≤15 and with E/E′ >15 had a 73.8% and 47.8% 1-year survival rate, respectively (p = 0.027). In the patients with an LVEF <50%, the patients with E/E′ ≤15 and those with E/E′ >15 demonstrated a 70.6% and 22.3% 1-year survival rate, respectively (p = 0.003). In multivariate analysis, significant predictors of mortality were E/E′ >15 and a combination of E/E′ >15 and B-type natriuretic peptide >300 ng/ml: adjusted mortality risk 2.34 (95% confidence interval (CI) 1.27 to 4.33, p = 0.0072) and 2.59 (95% CI 1.21 to 5.55, p = 0.014), respectively.ConclusionsThe E/E′ ratio is the single most predictive clinical and echo-Doppler parameter in the assessment of overall prognosis in patients with unoperated severe AS. LVEF was a significant predictor of survival only in the univariate analysis. B-type natriuretic peptide alone was not a predictor of prognosis in the study population. However, the combination of E/E′ and B-type natriuretic peptide is even more predictive of the 1-year prognosis

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years