In this subgroup analysis of STRONG-HF, we explored the association between changes in renal function and efficacy of rapid up-titration of guideline-directed medical therapy (GDMT) according to a high-intensity care (HIC) strategy. In patients randomized to the HIC arm (n = 542), renal function was assessed at baseline and during follow-up visits. We studied the association with clinical characteristics and outcomes of a decrease in estimated glomerular filtration rate (eGFR) at week 1, defined as ≥15% decrease from baseline. Patients in the usual care group (n = 536) were seen at day 90. The treatment effect of HIC versus usual care was independent of baseline eGFR (p-interaction = 0.4809). A decrease in eGFR within 1 week occurred in 77 (15.5%) patients and was associated with more rales on examination (p = 0.004), and a higher New York Heart Association class at the corresponding visit. Following the decrease in eGFR at 1 week, lower average optimal doses of GDMT were prescribed during follow-up (p = 0.0210) and smaller reductions in N-terminal pro-B-type natriuretic peptide occurred (geometrical mean 0.81 in no eGFR decrease vs 1.12 in GFR decrease, p = 0.0003). The rate of heart failure (HF) readmission or death at 180 days was 12.3% in no eGFR decrease versus 18.5% in eGFR decrease (p = 0.2274) and HF readmissions were 7.8% versus 16.6% (p = 0.0496). In the STRONG-HF study, HIC reduced 180-day HF readmission or death regardless of baseline eGFR. An early decrease in eGFR during rapid up-titration of GDMT was associated with more evidence of congestion, yet lower doses of GDMT during follow-up.

BackgroundSafety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies (STRONG-HF) demonstrated the safety and efficacy of rapid up-titration of guideline-directed medical therapy (GDMT) with high-intensity care (HIC) compared with usual care in patients hospitalized for acute heart failure (HF). In the HIC group, the following safety indicators were used to guide up-titration: estimated glomerular filtration rate of <30 mL/min/1.73 m2, serum potassium of >5.0 mmol/L, systolic blood pressure (SBP) of <95 mmHg, heart rate of <55 bpm, and N-terminal pro-B-type natriuretic peptide concentration of >10% higher than predischarge values. Methods and ResultsWe examined the impact of protocol-specified safety indicators on achieved dose of GDMT and clinical outcomes. Three hundred thirteen of the 542 patients in the HIC arm (57.7%) met ≥1 safety indicator at any follow-up visit 1–6 weeks after discharge. As compared with those without, patients meeting ≥1 safety indicator had more severe HF symptoms, lower SBP, and higher heart rate at baseline and achieved a lower average percentage of GDMT optimal doses (mean difference vs the HIC arm patients not reaching any safety indicator, –11.0% [95% confidence interval [CI] –13.6 to –8.4%], P < .001). The primary end point of 180-day all-cause death or HF readmission occurred in 15.0% of patients with any safety indicator vs 14.2% of those without (adjusted hazard ratio 0.84, 95% CI 0.48–1.46, P = .540). None of each of the safety indicators, considered alone, was significantly associated with the primary end point, but an SBP of <95 mm Hg was associated with a trend toward increased 180-day all-cause mortality (adjusted hazard ratio 2.68, 95% CI 0.94–7.64, P = .065) and estimated glomerular filtration rate decreased to <30 mL/min/1.73 m2 with more HF readmissions (adjusted hazard ratio 3.60, 95% CI 1.22–10.60, P = .0203). The occurrence of a safety indicator was associated with a smaller 90-day improvement in the EURO-QoL 5-Dimension visual analog scale (adjusted mean difference –3.32 points, 95% CI –5.97 to –0.66, P = .015). ConclusionsAmong patients with acute HF enrolled in STRONG-HF in the HIC arm, the occurrence of any safety indicator was associated with the administration of slightly lower GDMT doses and less improvement in quality of life, but with no significant increase in the primary outcome of 180-day HF readmission or death when appropriately addressed according to the study protocol.

The current surgical approach for patients with a single ventricle is the culmination of decades of dedicated research and groundbreaking innovation. From 1971 to the present day, a series of incremental advancements have significantly extended the life expectancy of these patients. Since the very beginning, Dr Guillermo Kreutzer and his team have pioneered different techniques with the ultimate goal of improving outcomes for these individuals. This is, narrated by him, the story of how it all began.

To assess the potential interaction between noncardiac comorbidities (NCCs) and the efficacy and safety of high intensity care (HIC) versus usual care (UC) in STRONG-HF trial, including stable patients with improved but still elevated NPs METHODS AND RESULTS: In the trial, 8 NCCs were reported: anemia, diabetes, renal dysfunction, severe liver disease, COPD/asthma, stroke/TIA, psychiatric/neurological disorders, and malignancies. Patients were classified by NCC number (0, 1, 2 and ≥3). The treatment effect of HIC versus UC on the primary endpoint, 180-day death or HF-rehospitalization, was compared by NCC number and by each individual comorbidity. Among the 1078 patients, the prevalence of 0, 1, 2 and ≥3 NCCs was 24.3%, 39.8%, 24.5% and 11.3%. Achievement of full doses of HF-therapies at 90- and 180-days in the HIC was similar irrespective of NCCs number. In the HIC, the primary endpoint occurred in 10.0%, 16,6%, 13,6% and 26,2%, in those with 0, 1, 2 and ≥3 NCCs, as compared to 19,1%, 25,4%, 23,3% and 26,2% in UC (interaction-p=0.80). The treatment benefit of HIC vs. UC on the primary endpoint didn't differ significantly by each individual comorbidity. There was no significant treatment interaction by NCC number in quality-of-life improvement (p=0.98) or the incidence of serious adverse events (p=0.11). In the STRONG-HF trial, non-cardiac comorbidities neither limited the rapid up-titration of HF-therapies, nor attenuated the benefit of HIC on primary endpoint. In the context of a clinical trial, the benefit-risk ratio favors the rapid up-titration of HF-therapies even in patients with multiple NCCs This article is protected by copyright. All rights reserved.

Children with moderate traumatic brain injury (modTBI) (Glasgow Coma Scale (GCS) 9-13) may benefit from better stratification. We aimed to compare neurocritical care utilization and functional outcomes between children with high GCS modTBI (hmodTBI, GCS 11-13), low GCS modTBI (lmodTBI, GCS 9-10), and severe TBI (sTBI, GCS ≤ 8). We hypothesized that patients with lmodTBI have higher neurocritical care needs and worse outcomes than patients with hmodTBI and are similar to patients with sTBI. Prospective observational study from June 2018 to October 2022 in 28 pediatric intensive care units (PICU) in Asia, South America, and Europe. We included children (age < 18years) with modTBI and sTBI admitted to PICU and measured functional outcomes at 3months using the Glasgow Outcome Scale-Extended Pediatric Revision (GOS-E Peds, scale 1-8, 1 = upper good recovery, 8 = death). We analyzed 409 patients: 98 (24%) and 311 (76%) with modTBI and sTBI, respectively. Patients with lmodTBI (vs. hmodTBI) were more likely to have invasive ICP monitoring (32.3% vs. 4.5%, p < 0.001), longer PICU stay (days, median [IQR]; 5.00 [4.00, 9.75] vs 4.00 [2.00, 5.00], p = 0.007), and longer hospital stay (days, median [IQR]: 13.00 [8.00, 17.00] vs. 8.00 [5.00, 12, 25], p = 0.015). Median GOS-E Peds scores were significantly different (hmodTBI (1.00 [1.00, 3.00]), lmodTBI (3.00 [IQR 2.00, 5.75]), and sTBI (5.00 [IQR 1.00, 6.00]) (p < 0.001)). After adjusting for age, sex, presence of polytrauma and cerebral edema, lmodTBI, and sTBI remained significantly associated with higher GOS-E scores (adjusted coefficient (standard error): 1.24 (0.52), p = 0.018, and 1.27 (0.33), p < 0.001, respectively) compared with hmodTBI. Children with lmodTBI have higher rates of neurocritical care utilization and worse functional outcomes than those with hmodTBI but better than those with sTBI. Children with lmodTBI may benefit from guideline-based management similar to what is implemented in children with sTBI. This work was performed in hospitals within the PACCMAN and LARed networks. No reprints will be ordered.

To develop a healthy diet score that is associated with health outcomes and is globally applicable using data from the Prospective Urban Rural Epidemiology (PURE) study and replicate it in five independent studies on a total of 245 000 people from 80 countries. A healthy diet score was developed in 147 642 people from the general population, from 21 countries in the PURE study, and the consistency of the associations of the score with events was examined in five large independent studies from 70 countries. The healthy diet score was developed based on six foods each of which has been associated with a significantly lower risk of mortality [i.e. fruit, vegetables, nuts, legumes, fish, and dairy (mainly whole-fat); range of scores, 0-6]. The main outcome measures were all-cause mortality and major cardiovascular events [cardiovascular disease (CVD)]. During a median follow-up of 9.3 years in PURE, compared with a diet score of ≤1 points, a diet score of ≥5 points was associated with a lower risk of mortality [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.63-0.77)], CVD (HR 0.82; 0.75-0.91), myocardial infarction (HR 0.86; 0.75-0.99), and stroke (HR 0.81; 0.71-0.93). In three independent studies in vascular patients, similar results were found, with a higher diet score being associated with lower mortality (HR 0.73; 0.66-0.81), CVD (HR 0.79; 0.72-0.87), myocardial infarction (HR 0.85; 0.71-0.99), and a non-statistically significant lower risk of stroke (HR 0.87; 0.73-1.03). Additionally, in two case-control studies, a higher diet score was associated with lower first myocardial infarction [odds ratio (OR) 0.72; 0.65-0.80] and stroke (OR 0.57; 0.50-0.65). A higher diet score was associated with a significantly lower risk of death or CVD in regions with lower than with higher gross national incomes (P for heterogeneity <0.0001). The PURE score showed slightly stronger associations with death or CVD than several other common diet scores (P < 0.001 for each comparison). A diet comprised of higher amounts of fruit, vegetables, nuts, legumes, fish, and whole-fat dairy is associated with lower CVD and mortality in all world regions, especially in countries with lower income where consumption of these foods is low.

The WHO Concept Model of Palliative Care emphasises empowering people and communities with Advance Care Planning (ACP). In Latin America, a more relational approach involving family members is suited to ACP. Improvements in doctor-patient-family relationships are needed. Policy efforts have been made to foster ACP in Argentina's healthcare system, but implementation barriers include a need for more communication skills and coordination between healthcare providers. The Shared Care Planning Group Argentina aims to promote ACP through research and training programs. It has sensitised and trained 236 healthcare providers in short courses to introduce basic information and skills. However, there needs to be specific documentation for ACP in Argentina. Research found obstacles to ACP implementation, such as the inability to converse with patients and the lack of coordination between healthcare teams. A new project will assess the self-efficacy of healthcare professionals who assist patients with Sclerosis Lateral Amyotrophic in ACP and evaluate a specific training program. Patient and public involvement in ACP remains limited in Argentina, with paternalistic medical culture and a need for more awareness and training among healthcare professionals as significant barriers. Collaborative research projects with Spain and Ecuador aim to train healthcare professionals and evaluate ACP implementation in other Latin American countries.

STRONG-HF examined a high-intensity care (HIC) strategy of rapid up-titration of guideline-directed medical therapy (GDMT) and close follow-up after acute heart failure (AHF) admission. We assess the role of age on efficacy and safety of HIC. Hospitalized AHF patients, not treated with optimal GDMT were randomized to HIC or usual care. The primary endpoint of 180-day death or HF readmission occurred equally in older (>65 years, n = 493, 74 ± 5 years) and younger patients (53 ± 11 years, adjusted hazard ratio [aHR] 1.02, 95% confidence interval [CI] 0.73-1.43, p = 0.89). Older patients received slightly lower GDMT to day 21, but same doses at day 90 and 180. The effect of HIC on the primary endpoint was numerically higher in younger (aHR 0.51, 95% CI 0.32-0.82) than older patients (aHR 0.73, 95% CI 0.46-1.15, adjusted interaction p = 0.30), partially related to COVID-19 deaths. After exclusion of COVID-19 deaths, the effect of HIC was similar in younger (aHR 0.51, 95% CI 0.32-0.82) and older patients (aHR 0.63, 95% CI 0.32-1.02, adjusted interaction p = 0.56), with no treatment-by-age interaction (interaction p = 0.57). HIC induced larger improvements in quality of life to day 90 in younger (EQ-VAS adjusted-mean difference 5.51, 95% CI 3.20-7.82) than in older patients (1.77, 95% CI -0.75 to 4.29, interaction p = 0.032). HIC was associated with similar rates of adverse events in older and younger patients. High-intensity care after AHF was safe and resulted in a significant reduction of all-cause death or HF readmission at 180 days across the study age spectrum. Older patients have smaller benefits in terms of quality of life.

The aim of this study was to evaluate efficacy and safety of rapid up-titration of guideline directed medical therapies in men and women hospitalized for acute heart failure (AHF). In STRONG-HF AHF patients were randomised just prior to discharge to either usual care (UC) or a high-intensity care (HIC) strategy of guideline-directed medical therapies (GDMT) up-titration. In these analyses, we compare the implementation, efficacy, and safety of the HIC strategy between men and women. In the randomised AHF population, 416/1078 (39%) were women. By day 90, a higher proportion of both sexes in the HIC group had been up-titrated to full doses of GDMT compared to UC. Overall, there were no differences in the primary endpoint between the sexes. The primary endpoint, 180-day HF readmission or death, occurred in 15.8% HIC women vs 23.5% women in the UC group (adjusted HR 0.67 [95% CI 0.40-1.13]) and in 14.9% HIC men vs 23.5% UC men (adjusted HR 0.57 [95% CI 0.38-0.88]), adjusted interaction p = 0.65. There was no significant treatment-by-sex interaction in quality-of-life improvement or in adverse events, including serious or fatal adverse events. The results of the current analyses suggest that a rapid up-titration of GDMT immediately after an AHF hospitalisation can and should be implemented similarly in men and women, as it results in reduction of 180-day all-cause death or HF readmission, quality-of-life improvement in both men and women with a similar safety profile.