Camilla Fuchs Andersen

Background: Heart failure (HF) prevalence is increasing. In a nationwide cohort study, we investigated temporal trends in care and outcomes of patients with new‐onset HF within vulnerable populations. Methods: There were 154 819 patients with new‐onset HF between 2003 and 2022 identified and included using Danish nationwide registries. Eight potentially vulnerable subgroups were defined (aged ≥80 years, women, low income, living alone, mental illness, non‐Western background, frail, and rural residency) and compared with their counterparts. Temporal trends in initiation of guideline‐recommended HF therapy and risk of all‐cause mortality were analyzed. Results: Initiation of guideline‐recommended HF therapies (mineralocorticoid‐receptor‐antagonists, β‐blockers, renin‐angiotensin system inhibitors) was generally successful, but initiation of mineralocorticoid receptor antagonists was insufficient in vulnerable patients. Five‐year all‐cause mortality decreased from 2003 to 2007 to 2018 to 2022; however, those aged ≥80 years, frail, and living alone experienced a smaller decrease (aged ≥80 years versus counterpart: adjusted hazard ratio [aHR], 0.74 [95% CI, 0.72–0.76] versus aHR, 0.63 [95% CI, 0.61–0.65]; frail versus counterpart: aHR, 0.74 [95% CI, 0.71–0.77] versus aHR, 0.67 [95% CI, 0.65–0.68]; living alone versus counterpart: aHR, 0.75 [95% CI, 0.73–0.77] versus aHR, 0.62 [95% CI, 0.60–0.64]); and patients with mental illness experienced no improvements (mental illness versus counterpart: aHR, 0.99 [95% CI, 0.87–1.12] versus aHR, 0.68 [95% CI, 0.67–0.70]). Six vulnerable groups had higher aHRs compared with their counterparts in 2018 to 2022. Conclusions: Initiation of guideline‐recommended therapies improved over the past 2 decades, but initiation of mineralocorticoid receptor antagonists was inadequate in vulnerable patients. Furthermore, the overall mortality risk declined, but 4 out of the 8 vulnerable groups experienced a lesser decline than their counterparts. Despite improvements, 6 vulnerable groups still had worse outcomes than their counterparts at the end of the study period. Our findings highlight the urgent need for more effort aimed at helping vulnerable subgroups of patients with HF.

Aims: Obesity increases the risk of heart failure (HF), partly due to hypervolaemia and excess epicardial adipose tissue (EAT). We aimed to investigate the effect of the sodium glucose co-transporter 2 inhibitor empagliflozin on estimated extracellular volume (eECV) and ventricular EAT mass in non-diabetic patients with overweight or obesity and risk of HF to evaluate the drug’s potential for HF prevention. Methods and results: In this randomized, double-blind, placebo-controlled trial, we recruited non-diabetic patients with body mass index (BMI) > 28 kg/m2 and risk of HF. Patients were randomized 1:1 to 180-day empagliflozin 10 mg or placebo. The primary endpoints were the baseline-adjusted mean differences in change of eECV and ventricular EAT mass in the intention-to-treat population with Bonferroni-adjustment for multiplicity. From September 2021 to July 2024, we randomized 191 patients (empagliflozin: 94, placebo: 97) with median age 68 years and median BMI 31.9 kg/m2. Analyses of eECV and EAT included 191 and 165 patients, respectively. Compared to placebo, empagliflozin significantly reduced eECV (empagliflozin, mean change [SD]: −0.154 L [0.257]; placebo, mean change: −0.029 L [0.261]; estimated treatment difference [ETD]: −0.123 L, 97.5% confidence interval [CI]: −0.211 to −0.035, Padj = 0.004) but did not affect EAT mass [empagliflozin, mean change: −2.3 g [13.4]; placebo, mean change: −3.7 g [15.8]; ETD: 1.5 g, 97.5% CI: −3.8 to 6.7, Padj = 1.00]. Conclusion: In high-risk patients with overweight or obesity, treatment with empagliflozin resulted in a potentially favourable reduction in eECV compared to placebo. Meanwhile, the drug did not affect EAT mass. Registration: ClinicalTrials.gov: NCT05042973

Background Obesity is common in heart failure with reduced ejection fraction (HFrEF). As anti-obesity treatments advance, understanding how body mass index (BMI) affects outcomes in HFrEF is increasingly important. Objective To examine whether a BMI >27 kg/m² is linked to higher risks of all-cause mortality, cardiovascular death, and heart failure (HF) hospitalization in HFrEF patients. Methods This study included 1,017 clinically stable, medically optimized HFrEF patients from the NorthStar study (2005–2009), followed through 2023 using Danish registries. Outcomes were assessed with Cox models adjusted for prognostic factors. The primary endpoint was all-cause mortality; secondary endpoints included cardiovascular death, HF hospitalization, and a composite of mortality or hospitalization. Subgroup analyses compared BMI categories (27 kg/m²). Results Patients with BMI >27 had more diabetes (27.8% vs. 17.7%) and lower NT-proBNP (median 776 vs. 1,163 pg/mL) than those with BMI 24–27, with similar HF etiology. Over a median 8.8 years, 821 patients (80.7%) died, including 444 cardiovascular deaths, and 740 (72.8%) were hospitalized for HF. A BMI of 35 vs. 27 was associated with non-significant increased all-cause mortality (HR 1.18, 95% CI 0.94–1.48) but significantly higher cardiovascular mortality (HR 1.42, 95% CI 1.05–1.92), HF hospitalization (HR 1.33, 95% CI 1.05–1.67), and composite outcome (HR 1.30, 95% CI 1.06–1.60). Subgroup analysis showed higher mortality with BMI >27 vs. 24–27 in ischemic cardiomyopathy (HR 1.31, 95% CI 1.05–1.64), but not in non-ischemic (HR 0.86, 95% CI 0.66–1.12), interaction p=0.015. Conclusion Among HFrEF patients—especially those with ischemic cardiomyopathy—BMI >27 is associated with worse outcomes, challenging the “obesity-survival paradox” and highlighting the importance of effective weight management.

Background: Heart failure (HF) and frailty often coexist. However, it is unknown how the interplay between HF and frailty at HF onset impacts prognosis of frail patients with HF and how this has evolved over time. Methods and Results: We identified 131 235 patients with new‐onset HF (median age 74 years, 39.7% women) from Danish nationwide registers in 1999 to 2017. Stratification according to the Hospital Frailty Risk Score resulted in (1) 102 635 (78%) nonfrail, (2) 26 054 (20%) moderately frail, and (3) 2609 (2%) severely frail patients. The proportion of moderately frail patients increased from 13.2% to 24.9%. Five‐year absolute risks of all‐cause mortality, HF hospitalization, and non‐HF hospitalization were calculated using the Kaplan‐Meier and Aalen‐Johansen estimators. From 1999 to 2002 to 2003 to 2017, all‐cause mortality risk (95% CI) declined from 56.4% (55.8%–57.0%) to 33.3% (32.6%–34.1%), 79.8% (78.5%–81.0%) to 58.6% (57.2%–60.1%), and 90.8% (85.6%–96.0%) to 79.8% (76.4%–83.2%) in nonfrail, moderately frail, and severely frail patients, respectively. HF hospitalization risk remained almost constant over the study period. Non‐HF hospitalization risk declined from 74.0% (73.5%–74.5%) to 65.8% (65.0%–66.5%) in nonfrail patients and remained stable overall in moderately frail and severely frail patients over the study period. Conclusions: We observed an increase in frail patients. Mortality decreased for all frailty groups but remained high for severely frail patients. These findings indicate the need for further evidence on the optimization of care for frail patients with HF, and future research should address the development of comprehensive management strategies, integrating frailty assessment into standard clinical care and focused care for older patients with HF.

Background: Given the many advances in treating heart failure (HF) and atrial fibrillation (AF) separately over the past decades, it remains unclear how the prognosis of patients diagnosed with both conditions has changed over time. We aimed to investigate the temporal trends in clinical outcomes from 1997 to 2018 in patients diagnosed with both HF and AF. Methods: From Danish nationwide registries, we identified 152,059 patients with a first-time HF-diagnosis from 1997 to 2018. Patients were grouped according to year of new-onset HF and AF-status: Prevalent AF (n=34,734), New-onset HF (n=12,691), and No AF (n=104,634). Outcomes of interest were the five-year risk of all-cause mortality, HF-hospitalization, and stroke. Results: Between 1997 and 2018, the proportion of patients with prevalent or new-onset AF increased from 24.7% (n=9256) to 35.8% (n=14,970). The five-year risk of all-cause mortality decreased from 69.1% (95% CI): 67.9%-70.2%) to 51.3% (49.9%-52.7%), 62.3% (60.5%-64.4%) to 43.0% (40.5%-45.5%), and 61.9% (61.3%-62.4%) to 36.7% (35.9%-37.6%) for the prevalent AF, new-onset AF, and no AF group, respectively. Minimal changes were observed in the risk of HF-hospitalization. The five-year risk of stroke decreased from 8.5% (7.8%-9.1%) to 5.0% (4.4%-5.5%) in the prevalent AF group, 8.2% (7.2%-9.2%) to 4.6% (3.7%-5.5%) in the new-onset AF group, and 6.3% (6.1%-6.6%) to 4.9% (4.6%-5.3%) in the no AF group. Simultaneously, patients prescribed anticoagulant therapy within 90 days after HF-onset increased from 42.7% to 93.1% in patients with prevalent AF and 41.9% to 92.5% in patients with new-onset AF. Conclusion: From 1997 to 2018, we observed an increase in patients with HF and coexisting AF. Mortality and stroke risk decreased across all patient groups regardless of AF-status. Anticoagulation therapy increased, and stroke risk in patients with HF and AF was reduced to similar levels as HF patients without AF at the end of the study period. Clinical Perspective: What is new?: In patients with heart failure, an increasing proportion had concomitant atrial fibrillation in 2018 versus 1997. The mortality- and stroke risk decreased for all patients with heart failure over the past two decades, also for patients with coexisting atrial fibrillation, and more patients received guideline-recommended therapy in 2018 versus in 1997. What are the clinical implications?: The increasing trend of patients with heart failure and coexisting atrial fibrillation necessitates a better understanding of the coexistence of these two conditions, of which this study provides insight into the evolving prognosis and management landscape of individuals with both heart failure and atrial fibrillation over the past two decades. Graphical