Francesc Formiga

Background and hypothesis: The association between acute declines in estimated glomerular filtration rate (eGFR) among individuals admitted for acute decompensated heart failure (ADHF) and cardiovascular outcomes has been inconsistent. Our objective was to examine whether eGFR decline and the timing of these declines are associated with mortality and a composite outcome of mortality or heart failure (HF) hospitalization. Methods: We used data from the CLOROTIC trial, which randomized patients admitted for ADHF to thiazide versus placebo. We examined % eGFR change at 2 days (n = 225) and at 4 days (n = 218) after randomization. Multivariable Cox models were used to evaluate the association between % eGFR change and a primary outcome of mortality and secondary outcome of composite of mortality or HF hospitalization. Results: Median % eGFR change was -9.7% (IQR -22.1, 5.4) and -14.4% (-25.1, 7.8) in the thiazide arm at 2 and 4 days, respectively, compared to -0.3% (-7.5, 10.1) and 0% (-10.0, 16.2) in the placebo arm at 2 and 4 days, respectively. Over a median 3-month follow-up, of those with 2-day eGFR change available, 41 (18%) patients died and 98 (44%) met the composite outcome, and of those with 4-day eGFR change available, 38 (17.4%) died and 95 (43.6%) met the composite outcome. The eGFR decline at 2 days was not associated with risk of mortality (hazard ratio [HR] = 0.96 [95% CI 0.47, 1.97] and HR = 0.89 [0.37, 2.10] per 30% eGFR decline in the thiazide and placebo arms, respectively). The eGFR decline at 4 days was not associated with risk of mortality in the thiazide arm (HR = 0.86 [0.48, 1.55] per 30% eGFR decline) nor in the placebo (HR = 1.63 [0.82, 3.26] per 30% eGFR decline). Associations were similar for the composite outcome. Conclusions: Among patients admitted for ADHF and randomized to thiazide versus placebo, early acute declines in eGFR had no association with increased risk of cardiovascular outcomes. Registration: Clinicaltrials.gov: NCT01647932; EudraCT Number: 2013-001852-36.

Background/Objectives: Heart failure (HF) is a leading cause of hospitalization in older adults, with significant sex differences in presentation, treatment, and outcomes. Transitional care models may benefit women more, yet they often receive less follow-up. This study assessed whether the clinical impact of the UMIPIC multidisciplinary HF management program differs by sex. Methods: This prospective, multicenter, observational cohort study included HF patients enrolled in the UMIPIC program or followed through conventional care in the RICA registry. Outcomes (30-day and one-year mortality and readmissions) were compared between groups, stratified by sex. Multivariate Cox models adjusted for age, HF phenotype, comorbidities, and baseline therapy. Results: A total of 5644 HF patients were included, with 2034 (36%) managed in UMIPIC and 3610 (64%) receiving conventional care. Women represented 55% of UMIPIC patients and were older, with higher prevalence of hypertension, anemia, and HF with preserved ejection fraction (HFpEF) compared to conventional care. At 30 days, women in UMIPIC had lower all-cause mortality (4.0% vs. 8.0%), cardiovascular mortality (2.0% vs. 6.0%), and readmissions (9.0% vs. 18.0%; all p < 0.01); these benefits persisted at one year. In multivariate analysis, UMIPIC enrollment remained protective (HR: 0.79; 95% CI: 0.71–0.87; p < 0.001). In men, UMIPIC patients were older with more comorbidities and higher HFpEF prevalence. They also showed lower 30-day mortality (2.0% vs. 8.0%; p < 0.05) and readmissions (8.0% vs. 18.0%; p < 0.01), with benefits maintained at one year. UMIPIC enrollment remained independently associated with reduced one-year mortality in men (HR: 0.79; 95% CI: 0.71–0.88; p < 0.001). Conclusions: The UMIPIC multidisciplinary care model reduced one-year mortality and readmissions in both women and men with HF, supporting integrated care strategies to improve outcomes in this high-risk population.

Background and Objectives: A COVID-19 model with a viral first-week phase and an inflammatory second phase has been proposed. It has been suggested that immunosuppressive treatment in the first week is harmful. This study aimed to analyze the potential damage of corticosteroids (CS) administered in the first week of COVID-19. Materials and Methods: This study was performed on a large cohort of consecutive COVID-19 patients admitted to Bellvitge University Hospital (Barcelona, Spain) from March 2020 to April 2021. Patients diagnosed with COVID-19 who were treated with 6 mg of dexamethasone a day for 10 days, and whose initiation of administration occurred within the first 2 weeks from symptom onset were included. We divided the cohort into the following two groups: patients for whom CS were initiated within the first 7 days after symptom onset vs. patients for whom CS were initiated between days 8 and 14. The degree of analytical inflammation (based on lymphocyte count, C-reactive protein, ferritin, lactate dehydrogenase, and D-dimer) upon admission was taken into account. The primary outcome was in-hospital mortality. Results: A total of 581 patients met the inclusion criteria. The results included, as follows: differences in age at baseline between groups (70.8 years old vs. 62.7, p < 0.001); moderate-to-severe dependency (11.9% vs. 4.2%, p = 0.003); the lymphocyte count (840 × 10⁶/L vs. 900, p = 0.033); D-dimer (400 ng/mL vs. 309, p < 0.001); and PaO₂/FiO₂ (290 vs. 311, p < 0.001). In-hospital mortality in patients who received CS in the first week of symptom onset was higher (29% vs. 12.8%, p < 0.001). The following risk factors were associated with higher in-hospital mortality: age (OR = 1.06, p < 0.001); Charlson index (OR = 1.34, p = 0.001); tachypnea > 20 bpm (OR = 2.58, p < 0.001); ≥3 high-risk criteria of inflammation (OR = 1.94, p = 0.012); and CS onset in the first week (OR = 2.17, p = 0.004). A higher PaO₂/FiO₂ (OR = 0.99, p < 0.001) and the use of remdesivir (OR = 0.53, p = 0.021) were identified as protective factors. However, when stratified by analytical inflammation criteria, the onset of CS in the first week did not reach statistical significance. Conclusions: The early administration of CS did not demonstrate a significant detrimental effect. These results highlight the need for a nuanced approach to CS therapy in COVID-19 that carefully weighs the risks and benefits based on individual patient characteristics and the severity of the inflammation.

Background and Objectives: Previous studies showed that, paradoxically, obese patients with heart failure (HF) have better clinical outcomes compared to overweight, normal, or underweight patients. Scientific societies emphasize the importance of integrating quality of life (QoL) assessment in cardiovascular care. However, the association between QoL and weight remains understudied. Given the significant correlation between HF survival and QoL, it is essential to assess how obesity impacts patient-reported outcomes in this clinical setting. Methods: This cross-sectional multicenter study in 1028 HF patients with reduced ejection fraction (HFrEF) aims to evaluate the association between obesity and QoL, and whether the obesity paradox holds for HF patients regarding QoL. Specific and generic QoL questionnaires were administered alongside clinical parameters like body mass index (BMI) and body adiposity estimator (BAE). Results: Obese compared to non-obese reported worse QoL. In the adjusted linear regression models, neither BMI nor obesity were associated with QoL. Generalized additive models confirmed a strong non-parametric association between BMI, subdomain scores from Kansas City Cardiomyopathy Questionnaire (KCCQ) (OSS p = 0.004, CSS p = 0.006, TSS p = 0.02), and summary measurements of EQ-5D (EQ-5D index p = 0.003, visual analogue scale (VAS) p = 0.01). In contrast, BAE showed a statistically significant linear relation among QoL (OSS p ≤ 0.001, CSS p ≤ 0.001, TSS p ≤ 0.001) and EQ-5D summary measurements (EQ-5D index p ≤ 0.001, VAS p ≤ 0.001). Conclusions: Overall, obese patients have worse QoL; therefore, obesity cannot be considered a protective factor in terms of QoL in established HF.

Plasma osteopontin is a promising aging-related biomarker among individuals with and without kidney disease. The interaction between sex, pOPN levels, and global and cardio-renal outcomes among older individuals was not previously evaluated. In this study we investigated the association of pOPN with 24-month global, major cardiovascular events (MACEs), MACE + cardiovascular (CV) mortality, and renal decline among older individuals; we also evaluated whether sex modified observed associations. pOPN levels were measured in a cohort of 2 013 outpatients (908 men and 1 105 women) aged 75 years or more enrolled in the context of a multicenter prospective cohort study in Europe. Multivariable linear regression, Cox and Fine Gray models, and linear mixed regression models were fitted to evaluate whether sex modified the associations between biomarkers and study outcomes. 2 013 older participants with a median age of 79 years, and 54.9% women were included in the study; increased pOPN levels were associated with all-cause mortality specifically among women (reduced fully-adjusted model resulting from backward selection, HR, 95%CI: 1.84, 1.20–2.89). Addition of pOPN to models containing age, eGFR, and ACR improved time-dependent AUC at 6, 12, and 24 months, among women only. No significant association was found between the biomarker levels, MACE, and MACE + CV mortality. Conversely, increased baseline pOPN was associated with eGFR decline in all patients (-0.45, 95%CI:-0.68 to -0.22 ml/min/1.73 m² year) but with slightly steeper declines in women compared to men (-0.57, -0.99 to -0.15 vs -0.47, -0.88 to -0.07). pOPN levels were significantly lower in women than in men but associated with all-cause mortality in women only; increase in serum pOPN was associated with eGFR decline over time in all patients, but with stronger associations among women. Assessment of pOPN may help identifying older female participants at risk of poor outcomes.

Purpose: In this study, a comprehensive analysis of costs of chronic kidney disease (CKD) was performed, to understand factors associated with the economic burden of the disease in a multicentre international framework. Methods: The impact on costs of demographics, socio-economics, clinical, and functional variables was tested in 2204 subjects aged 75 years or more attending outpatient clinics in Europe using a multicentre 2-year prospective cohort study. By means of collected resources consumption and unit cost data a comprehensive cost database was built and then investigated using multilevel regression modeling. Results: Overall, hospitalization, medications and specialist visits were the main cost items, with a notable variability among countries. Estimated yearly costs were 4478€ ± 9804€, rising up to 6683€ ± 10,953€ for subjects with estimated Glomerular Filtration Rate (eGFR) < 30. Costs increased significantly according to the severity of the disease, gender and age. Clinical and functional covariates were also significantly associated with CKD-related total costs, even after correcting for the inter-country variability. Conclusion: Findings corroborate the importance of multidimensional assessment of participants with CKD, as multimorbidity and functional disability produce a detrimental impact on participant’s prognosis and cost of care. Preservation of functional impairment and adequate management of comorbidities may thus help decreasing the overall consumption on health care resources in CKD patients, especially in older people.

Background: Heart failure (HF) with preserved ejection fraction (pEF) has lacked effective treatments for reducing mortality. However, previous studies have found an association between statin use and decreased mortality in patients with HFpEF. The aim of this study was to analyse whether statin therapy is associated with a reduction in mortality in these patients and whether the effect differs according to the presence or absence of ischaemic heart disease (IHD). Methods: We analysed data from the National Registry of Heart Failure, a prospective study that included patients admitted for HF in Internal Medicine units nationwide. Patients with HFpEF were classified according to the use of statins, and the differences between the two groups were analysed. A multivariable analysis was performed using Cox regression to assess factors independently related to mortality. Results: A total of 2788 patients with HFpEF were included; 63% of them were women with a mean age of 80.1 (±7.8) years. The statin-treated group (40.2%) was younger, with better functional status, and had a more common diagnosis of vascular disease and lower frequency of atrial fibrillation. The most frequent aetiology of HF in both groups was the hypertensive one. Nevertheless, ischaemic HF was more common in those who received statins (24.8% vs. 9.6%; p < 0.001). Multivariable analysis showed lower mortality at the 1-year follow-up in statin-treated patients (OR: 0.74; 95%CI: 0.61–0.89; p = 0.002). This association was observed in patients without IHD (p < 0.001) but not in those with IHD (p = 0.11). Conclusions: Statins are associated with a decrease in total mortality in patients with HFpEF. This benefit occurs mainly in those without IHD.