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Background: Sleep apnea is more common in patients with heart failure (HF) than in the general population, but little is known about its association with clinical outcomes in various HF phenotypes or how it might modify the effect of HF therapy. Objectives: To examine the prevalence of sleep apnea, its association with outcomes and the effects of dapagliflozin in patients with HF with and without sleep apnea in a pooled analysis of 2 trials comparing dapagliflozin to placebo in HFrEF (DAPA-HF trial) and HFmrEF/HFpEF (DELIVER trial). Methods: A history of sleep apnea was investigator-reported. The primary outcome was a composite of worsening HF or cardiovascular death. Results: The prevalence of sleep apnea was 5.7% and 7.8% in patients with HFrEF and HFmrEF/HFpEF, respectively. The primary outcome occurred at a rate of 16.0 in participants with sleep apnea compared to 10.6 per 100 person-years in those without (adjusted HR 1.29 [95%CI, 1.10–1.52]). Compared with placebo, dapagliflozin reduced the risk of the primary endpoint to the same extent in patients with (HR 0.78 [95% CI, 0.59–1.03]) and without sleep apnea (HR 0.79 [0.72–0.87]) [Pinteraction = 0.93]. The beneficial effects of dapagliflozin on other clinical outcomes and symptom burden, physical function, and quality of life were consistent in participants with and without sleep apnea. Conclusions: In DAPA-HF and DELIVER, the true prevalence of sleep apnea was likely underestimated. An investigator-reported history of sleep apnea was associated with higher rates of worsening HF events. The benefits of dapagliflozin on clinical outcomes were consistent in patients with and without sleep apnea. Clinical trial registration: Unique identifiers: NCT01920711 Condensed Abstract: In a pooled analysis of the DAPA-HF and DELIVER trials of more than 11,000 patients with heart failure (HF) across the range of ejection fractions, an investigator-reported history of sleep apnea was associated with higher rates

Aim: Blood urea nitrogen (BUN) to creatinine ratio is associated with worse outcomes in acute heart failure (HF) but little is known about its importance in chronic HF. Methods and results: We combined individual patient data from clinical trials (HF with reduced ejection fraction [HFrEF]: PARADIGM-HF, ATMOSPHERE and DAPA-HF, and HF with preserved ejection fraction [HFpEF]: PARAGON-HF and I-PRESERVE). The primary outcome examined was a composite time to first HF hospitalization or cardiovascular death; its components and all-cause death were also examined. Each HF phenotype was categorized according to median BUN/creatinine ratio, generating four groups that is, HFpEF ≤ and >median BUN/creatinine ratio and HFrEF ≤ and >median BUN/creatinine ratio. The association between BUN/creatinine ratio and outcomes was evaluated using the Kaplan–Meier estimator and Cox proportional hazard models. Overall, 28 820 patients were analysed. The median (IQR) BUN/creatinine ratio was 20.1 (Q1–Q3 16.7–24.7) in HFpEF and 18.7 (15.2–22.8) in HFrEF. In both HFpEF and HFrEF, higher BUN/creatinine ratio was associated with older age, female sex, and diabetes, but similar estimated glomerular filtration rate (eGFR). The risk of each outcome examined was significantly higher in patients with BUN/creatinine ratio ≥median, compared to

Background The incidence and distribution of acute and chronic dialysis among patients with heart failure (HF), stratified by diabetes, remain uncertain. We hypothesized that with improved survival and rising comorbidities, the demand for dialysis would increase over time. Methods and Results Patients with incident HF, aged 18 to 100 years, between 2002 and 2016, were identified using Danish nationwide registers. Primary outcomes included acute and chronic dialysis initiation, HF‐related hospitalization, and all‐cause mortality. These outcomes were assessed in 2002 to 2006, 2007 to 2011, and 2012 to 2016, stratified by diabetes. We calculated incidence rates (IRs) per 1000 person‐years and hazard ratios (HR) using multivariable Cox regression. Of 115 533 patients with HF, 2734 patients received acute dialysis and 1193 patients received chronic dialysis. The IR was 8.0 per 1000 and 3.5 per 1000 person‐years for acute and chronic dialysis, respectively. Acute dialysis rates increased significantly among patients with diabetes over time, while no significant changes occurred in those without diabetes, chronic dialysis, HF‐related hospitalization, or overall mortality. Diabetes was associated with significantly higher HRs of acute and chronic dialysis, respectively, compared with patients without diabetes (HR, 2.07 [95% CI, 1.80–2.39] and 2.93 [95% CI, 2.40–3.58] in 2002 to 2006; HR, 2.45 [95% CI, 2.14–2.80] and 2.86 [95% CI, 2.32–3.52] in 2007 to 2011; and 2.69 [95% CI, 2.33–3.10] and 3.30 [95% CI, 2.69–4.06] in 2012 to 2016). Conclusions The IR of acute and chronic dialysis remained low compared with HF‐related hospitalizations and mortality. Acute dialysis rates increased significantly over time, contrasting no significant trends in other outcomes. Diabetes exhibited over 2‐fold increased rates of the outcomes. These findings emphasize the importance of continued monitoring and renal care in patients with HF, especially with diabetes, to, BACKGROUND: The incidence and distribution of acute and chronic dialysis among patients with heart failure (HF), stratified by diabetes, remain uncertain. We hypothesized that with improved survival and rising comorbidities, the demand for dialysis would increase over time. METHODS AND RESULTS: Patients with incident HF, aged 18 to 100 years, between 2002 and 2016, were identified using Danish nationwide registers. Primary outcomes included acute and chronic dialysis initiation, HF-related hospitalization, and all-cause mortality. These outcomes were assessed in 2002 to 2006, 2007 to 2011, and 2012 to 2016, stratified by diabetes. We cal-culated incidence rates (IRs) per 1000 person-years and hazard ratios (HR) using multivariable Cox regression. Of 115 533 patients with HF, 2734 patients received acute dialysis and 1193 patients received chronic dialysis. The IR was 8.0 per 1000 and 3.5 per 1000 person-years for acute and chronic dialysis, respectively. Acute dialysis rates increased significantly among patients with diabetes over time, while no significant changes occurred in those without diabetes, chronic dialysis, HF-related hospitalization, or overall mortality. Diabetes was associated with significantly higher HRs of acute and chronic dialysis, re-spectively, compared with patients without diabetes (HR, 2.07 [95% CI, 1.80–2.39] and 2.93 [95% CI, 2.40–3.58] in 2002 to 2006; HR, 2.45 [95% CI, 2.14–2.80] and 2.86 [95% CI, 2.32–3.52] in 2007 to 2011; and 2.69 [95% CI, 2.33–3.10] and 3.30 [95% CI, 2.69–4.06] in 2012 to 2016). CONCLUSIONS: The IR of acute and chronic dialysis remained low compared with HF-related hospitalizations and mortality. Acute dialysis rates increased significantly over time, contrasting no significant trends in other outcomes. Diabetes exhibited over 2-fold increased rates of the outcomes. These findings emphasize the importance of continued monitoring and renal care in patients with HF, especially with diabetes, to optimize outcomes and

Background: A sizeable proportion of patients with chronic kidney disease (CKD) are reported to be frail. Here we examined the safety andefficacy of dapagliflozin in patients with CKD by frailty level.Methods: Adults with CKD, with/without type 2 diabetes, with an estimated glomerular filtration rate (eGFR) of 25–75 mL/min/1.73 m2 , andurinary albumin-to-creatinine ratio 200–5 000 mg/g were randomized to dapagliflozin (10 mg/day) or placebo. The primary endpoint was a com-posite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD), or death from kidney or cardiovascular (CV) causes.Results: Frailty index (FI), assessed by Rockwood cumulative deficit approach, was calculable in 4 303/4 304 (99.9%) patients: 1 162 (27.0%)in not-to-mildly frail (FI ≤0.210), 1 642 (38.2%) in moderately frail (FI 0.211–0.310), and 1 499 (34.8%) in severely frail categories (FI >0.311).Dapagliflozin reduced the risk of the primary composite endpoint across all FI categories (hazard ratios [95% confidence interval {CI}]: 0.50[0.33–0.76], 0.62 [0.45–0.85], and 0.64 [0.49–-0.83], respectively; p-interaction = 0.67). Results were similar for secondary outcomes includ-ing kidney composite outcome (sustained ≥50% eGFR decline, ESKD or death from kidney cause; p-interaction = 0.44), CV endpoint (heartfailure hospitalization or CV death; p-interaction = 0.63), and all-cause mortality (p-interaction p = .42). Results were consistent when usingFI as a continuous variable. Occurrence of serious adverse events was numerically lower in patients receiving dapagliflozin versus placeboin all FI categories (16.9% vs 20.1%, 26.3% vs 30.7%, and 42.9% vs 47.8%, in not-to-mildly, moderately, and severely frail categories,respectively).Conclusions: The relative benefit of dapagliflozin for all outcomes was consistent across all frailty categories, with no difference in associatedsafety., BACKGROUND: A sizeable proportion of patients with chronic kidney disease (CKD) are reported to be frail. Here we examined the safety and efficacy of dapagliflozin in patients with CKD by frailty level.METHODS: Adults with CKD, with/without type 2 diabetes, with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m 2 and urinary albumin-to-creatinine ratio 200-5000 mg/g were randomized to dapagliflozin (10 mg/day) or placebo. The primary endpoint was composite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD) or death from kidney or cardiovascular (CV) causes.RESULTS: Frailty index (FI), assessed by Rockwood cumulative deficit approach, was calculable in 4303/4304 (99.9%) patients: 1162 (27.0%) in not-to-mildly frail(FI≤0.210), 1642 (38.2%) in moderately frail(FI 0.211-0.310), and 1499 (34.8%) in severely frail categories (FI>0.311). Dapagliflozin reduced the risk of the primary composite endpoint across all FI categories (hazard ratios [95% CI]: 0.50 [0.33-0.76], 0.62 [0.45-0.85], and 0.64 [0.49-0.83], respectively (P-interaction =0.67). Results were similar for secondary outcomes including kidney composite outcome (sustained ≥50% eGFR decline, ESKD or death from kidney cause; P-interaction=0.44), CV endpoint (heart failure hospitalization or CV death; P-interaction=0.63), and all-cause mortality (P-interaction p=0.42). Results were consistent when using FI as a continuous variable. Occurrence of serious adverse events was numerically lower in patients receiving dapagliflozin vs. placebo in all FI categories (16.9% vs. 20.1%, 26.3% vs. 30.7%, and 42.9% vs 47.8%, in not-to-mildly, moderately and severely frail categories, respectively).CONCLUSIONS: The relative benefit of dapagliflozin for all outcomes was consistent across all frailty categories, with no difference in associated safety.

BACKGROUND: Patients with heart failure and chronic kidney disease (CKD) may have an increased risk of death from causes competing with arrhythmic death, which could have implications for the efficacy of implantable cardioverter-defibrillators (ICDs). We examined the long-term effects of primary prophylactic ICD implantation, compared with usual care, according to baseline CKD status in an extended follow-up study of DANISH (Danish Study to Assess the Efficacy of ICDs in Patients With Nonischemic Systolic Heart Failure on Mortality).METHODS AND RESULTS: In the DANISH trial, 1116 patients with nonischemic heart failure with reduced ejection fraction were randomized to receive an ICD (N=556) or usual care (N=550). Outcomes were analyzed according to CKD status (estimated glomerular filtration rate ≥/<60 mL/min per 1.73 m 2) at baseline. In total, 1113 patients had an available estimated glomerular filtration rate measurement at baseline (median estimated glomerular filtration rate 73 mL/min per 1.73 m 2), and 316 (28%) had CKD. During a median follow-up of 9.5 years, ICD implantation, compared with usual care, did not reduce the rate of all-cause mortality (no CKD, HR, 0.82 [95% CI, 0.64-1.04]; CKD, HR, 1.02 [95% CI, 0.75-1.38]; P interaction=0.31) or cardiovascular death (no CKD, HR, 0.77 [95% CI, 0.58-1.03]; CKD, HR, 1.05 [95% CI, 0.73-1.51]; P interaction=0.20), irrespective of baseline CKD status. Similarly, baseline CKD status did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (no CKD, HR, 0.57 [95% CI, 0.32-1.00]; CKD, HR, 0.65 [95% CI, 0.34-1.24]; P interaction=0.70). CONCLUSIONS: ICD implantation, compared with usual care, did not reduce the overall mortality rate, but it did reduce the rate of sudden cardiovascular death, regardless of baseline kidney function in patients with nonischemic heart failure with reduced ejection fraction.REGISTRATION: URL: https://www.clinicaltrials.gov; Unique ident