[Acute heart failure (AHF)].

INTRODUCTION: Acute heart failure (AHF) is a frequent cause for emergency consultations, leads to long hospital stays and is characterized by high mortality and rehospitalization rates, with the first months after hospitalization having the highest risk («vulnerable phase¼). The clinical presentation is usually characterized by fluid accumulation. Over the last three decades, few advances have been achieved in the treatment of AHF, as most studies with diuretics or vasodilators failed to show positive effects in terms of mortality and rehospitalization rates. In this context, the treatment of AHF must have an integrative approach, consisting of rapid correction of systemic congestion on the one hand, and specific therapies for the precipitating factors, the underlying cardiac pathology, and non-cardiac comorbidities on the other. Recently, it has been shown that a rapid and intensive up-titration of oral heart failure medical therapy during and immediately after hospitalization can improve the prognosis during the vulnerable phase after AHF. In this article, the principles of optimization and personalization of diuretic therapy and oral heart failure medication during hospitalization and the early outpatient phase after AHF are discussed.

Characteristics, treatment, and outcomes of early vs. late enrollees of the STRONG-HF trial.

BACKGROUND: The STRONG-HF trial showed that high-intensity care (HIC) consisting of rapid up-titration of guideline-directed medical therapy (GDMT) and close follow-up reduced all-cause death or heart failure (HF) readmission at 180 days compared to usual care (UC). We hypothesized that significant differences in patient characteristics, management, and outcomes over the enrolment period may exist. METHODS: Two groups of the 1,078 patients enrolled in STRONG-HF were created according to the order of enrolment within center. The early group consisted of the first 10 patients enrolled at each center (N = 342) and the late group consisted of the following patients (N = 736). RESULTS: Late enrollees were younger, had more frequently reduced ejection fraction, slightly lower NT-proBNP and creatinine levels compared with early enrollees. The primary outcome occurred less frequently in early compared to late enrollees (15% vs. 21%, aHR 0.65, 95% CI 0.42-0.99, P = .044). No treatment-by-enrolment interaction was seen in respect to the average percentage of optimal dose of GDMT after randomization, which was consistently higher in early and late patients randomized to HIC compared to UC. The higher use of renin-angiotensin-inhibitors in the HIC arm was more pronounced in the late enrollees both after randomization (interaction-P = .013) and at 90 days (interaction-P < .001). No interaction was observed for safety events. Patients randomized late to UC displayed a trend toward more severe outcomes (26% vs. 16%, P = .10), but the efficacy of HIC showed no interaction with the enrolment group (aHR 0.77, 95% CI 0.35-1.67 in early and 0.58, 95% CI 0.40-0.83 in late enrollees, adjusted interaction-P = .51) with similar outcomes in the HIC arm in late and early enrollees (16% vs. 13%, P = .73). CONCLUSIONS: Late enrollees have different clinical characteristics and higher event rates compared to early enrollees. GDMT implementation in the HIC arm robustly achieved similar doses with consistent efficacy in early and late enrollees, mitigating the higher risk of adverse outcome in late enrollees. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03412201.

Titration of Medications after Acute Heart Failure is Safe, Tolerated, and Effective Regardless of Risk.

BACKGROUND: Guideline-directed medical therapy decisions may be less affected by single patient variables such as blood pressure or kidney function and more by overall risk profile. In STRONG-HF, high intensity care (HIC) in the form of rapid uptitration of heart failure (HF) guideline-directed medical therapy (GDMT) was effective overall, but the safety, tolerability and efficacy of HIC across the spectrum of HF severity is unknown. Evaluating this with a simple risk-based framework offers an alternative and more clinically translatable approach than traditional subgroup analyses. OBJECTIVES: To assess safety, tolerability, and efficacy of HIC according to the simple, powerful, and clinically translatable Meta-Analysis Global Group in Chronic (MAGGIC) HF risk score. METHODS: In STRONG-HF, 1078 patients with acute HF were randomized to HIC (uptitration of treatments to 100% of recommended doses within 2 weeks of discharge and 4 scheduled outpatient visits over the 2 months after discharge) versus usual care (UC). The primary endpoint was the composite of all-cause death or first HF rehospitalization at Day 180. Baseline HF risk profile was determined by the previously validated MAGGIC risk score. Treatment effect was stratified according to MAGGIC risk score both as a categorical and continuous variable. RESULTS: Among 1062 patients (98.5%) with complete data for whom a MAGGIC score could be calculated at baseline, GDMT use at baseline was similar across MAGGIC tertiles. Overall GDMT prescriptions achieved for individual medication classes were higher in the HIC versus UC group and did not differ by MAGGIC risk score tertiles (interaction non-significant). The incidence of all-cause death or HF readmission at Day 180 was, respectively, 16.3%, 18.9%, and 23.2% for MAGGIC risk score tertiles 1-3. The HIC arm was at lower risk of all-cause death or HF readmission at Day 180 (HR 0.66, 95% CI 0.50-0.86) and this finding was robust across MAGGIC risk score modeled as a categorical (HR 0.51, 0.62, 0.68 in tertile 1, 2, and 3, respectively, (interaction non-significant) for all comparisons) and continuous (p-interaction=NS) variable. The rate of adverse events was higher in the HIC group, but this observation did not differ based on MAGGIC risk score tertile (interaction non-significant). CONCLUSIONS: HIC led to better use of GDMT and lower HF-related morbidity and mortality compared to UC regardless of underlying HF risk profile.

Blood pressure and intensive treatment up-titration after acute heart failure hospitalization: Insights from the STRONG-HF trial.

AIMS: A high-intensity care (HIC) strategy with rapid guideline-directed medical therapy (GDMT) up-titration and close follow-up visits improved outcomes, compared to usual care (UC), in patients recently hospitalized for acute heart failure (AHF). Hypotension is a major limitation to GDMT implementation. We aimed to assess the impact of baseline systolic blood pressure (SBP) on the effects of HIC versus UC and the role of early SBP changes in STRONG-HF. METHODS AND RESULTS: A total of 1075 patients hospitalized for AHF with SBP ≥100 mmHg were included in STRONG-HF. For the purpose of this post-hoc analysis, patients were stratified by tertiles of baseline SBP (<118, 118-128, and ≥129 mmHg) and, in the HIC arm, by tertiles of changes in SBP from the values measured before discharge to those measured at 1 week after discharge (≥2 mmHg increase, ≤7 mmHg decrease to <2 mmHg increase, and ≥8 mmHg decrease). The primary endpoint was 180-day heart failure rehospitalization or death. The effect of HIC versus UC on the primary endpoint was independent of baseline SBP evaluated as tertiles (pinteraction = 0.77) or as a continuous variable (pinteraction = 0.91). In the HIC arm, patients with increased, stable and decreased SBP at 1 week reached 83.5%, 76.2% and 75.3% of target doses of GDMT at day 90. The risk of the primary endpoint was not significantly different between patients with different SBP changes at 1 week (adjusted p = 0.46). CONCLUSIONS: In STRONG-HF, the benefits of HIC versus UC were independent of baseline SBP. Rapid GDMT up-titration was performed also in patients with an early SBP drop, resulting in similar 180-day outcome as compared to patients with stable or increased SBP.

Impact of Rapid Up-Titration of Guideline-Directed Medical Therapies on Quality of Life: Insights From the STRONG-HF Trial.

BACKGROUND: This analysis provides details on baseline and changes in quality of life (QoL) and its components as measured by EQ-5D-5L questionnaire, as well as association with objective outcomes, applying high-intensity heart failure (HF) care in patients with acute HF. METHODS: In STRONG-HF trial (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies) patients with acute HF were randomized just before discharge to either usual care or a high-intensity care strategy of guideline-directed medical therapy up-titration. Patients ranked their state of health on the EQ-5D visual analog scale score ranging from 0 (the worst imaginable health) to 100 (the best imaginable health) at baseline and at 90 days follow-up. RESULTS: In 1072 patients with acute HF with available assessment of QoL (539/533 patients assigned high-intensity care/usual care) the mean baseline EQ-visual analog scale score was 59.2 (SD, 15.1) with no difference between the treatment groups. Patients with lower baseline EQ-visual analog scale (meaning worse QoL) were more likely to be women, self-reported Black and non-European (P<0.001). The strongest independent predictors of a greater improvement in QoL were younger age (P<0.001), no HF hospitalization in the previous year (P<0.001), lower NYHA class before hospital admission (P<0.001) and high-intensity care treatment (mean difference, 4.2 [95% CI, 2.5-5.8]; P<0.001). No statistically significant heterogeneity in the benefits of high-intensity care was seen across patient subgroups of different ages, with left ventricular ejection fraction above or below 40%, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and systolic blood pressure above or below the median value. The treatment effect on the primary end point did not vary significantly across baseline EQ-visual analog scale (Pinteraction=0.87). CONCLUSIONS: Early up-titration of guideline-directed medical therapy significantly improves all dimensions of QoL in patients with HF and improves prognosis regardless of baseline self-assessed health status. The likelihood of achieving optimal doses of HF medications does not depend on baseline QoL. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03412201.

Multiple Abscess Collections: Antibiotics or Steroids?

Aseptic abscess syndrome (AAS) is a medical rarity. The combination of multiple abscess collections in different organs, negative microbiological studies, and the association with an inflammatory bowel disease is highly suggestive for an AAS. The AAS is an acute neutrophilic dermatosis, so "generalized pyoderma gangraenosum" or "generalized bullous sweet syndrome" might be used synonymously. It is important to note that the diagnosis of an AAS can be made only after careful exclusion of an infectious disease. Of interest, despite the severity of the inflammation, patients with AAS are commonly hemodynamically stable. To date, no studies have investigated the optimal regimen, dose, and duration of therapy. Corticosteroids are the cornerstone of immunosuppression during the acute phase. After the induction phase, therapy might be switched to anakinra or infliximab.

Experimentally Induced Peripheral Venous Congestion Exacerbates Inflammation, Oxidative Stress, and Neurohormonal and Endothelial Cell Activation in Patients With Systolic Heart Failure.

BACKGROUND: Venous congestion (VC) is a hallmark of symptomatic heart failure (HF) requiring hospitalization; however, its role in the pathogenesis of HF progression remains unclear. We investigated whether peripheral VC exacerbates inflammation, oxidative stress and neurohormonal and endothelial cell (EC) activation in patients with HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Two matched groups of patients with HFrEF and with no peripheral VC vs without recent HF hospitalization were studied. We modeled peripheral VC by inflating a cuff around the dominant arm, targeting ∼ 30 mmHg increase in venous pressure (venous stress test [VST]). Blood and ECs were sampled before and after 90 minutes of VST. We studied 44 patients (age 53 ± 12 years, 32% female). Circulating endothelin-1, tumor necrosis factor-α, interleukin-6, isoprostane, angiotensin II (ang-2), angiopoietin-2, vascular cell adhesion molecule-1, and CD146 significantly increased after the VST. Enhanced endothelin-1 and angiopoietin-2 responses to the VST were present in patients with vs without recent hospitalization and were prospectively associated with incident HF-related events; 6698 messenger ribonucleic acid (mRNA probe sets were differentially expressed in ECs after VST. CONCLUSIONS: Experimental VC exacerbates inflammation, oxidative stress, neurohormonal and EC activation and promotes unfavorable transcriptome remodeling in ECs of patients with HFrEF. A distinct biological sensitivity to VC appears to be associated with high risk for HF progression.

Safety Indicators in Patients Receiving High-intensity Care After Hospital Admission for Acute Heart Failure: The STRONG-HF Trial.

BACKGROUND: Safety, 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 RESULTS: We 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). CONCLUSIONS: Among 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.

Diagnosis and treatment of right ventricular failure secondary to acutely increased right ventricular afterload (acute cor pulmonale): a clinical consensus statement of the Association for Acute CardioVascular Care of the European Society of Cardiology.

Acute right ventricular failure secondary to acutely increased right ventricular afterload (acute cor pulmonale) is a life-threatening condition that may arise in different clinical settings. Patients at risk of developing or with manifest acute cor pulmonale usually present with an acute pulmonary disease (e.g. pulmonary embolism, pneumonia, and acute respiratory distress syndrome) and are managed initially in emergency departments and later in intensive care units. According to the clinical setting, other specialties are involved (cardiology, pneumology, internal medicine). As such, coordinated delivery of care is particularly challenging but, as shown during the COVID-19 pandemic, has a major impact on prognosis. A common framework for the management of acute cor pulmonale with inclusion of the perspectives of all involved disciplines is urgently needed.

Optimization of Evidence-Based Heart Failure Medications After an Acute Heart Failure Admission: A Secondary Analysis of the STRONG-HF Randomized Clinical Trial.

Importance: The Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by N-Terminal Pro-Brain Natriuretic Peptide Testing of Heart Failure Therapies (STRONG-HF) trial strived for rapid uptitration aiming to reach 100% optimal doses of guideline-directed medical therapy (GDMT) within 2 weeks after discharge from an acute heart failure (AHF) admission. Objective: To assess the association between degree of GDMT doses achieved in high-intensity care and outcomes. Design, Setting, and Participants: This was a post hoc secondary analysis of the STRONG-HF randomized clinical trial, conducted from May 2018 to September 2022. Included in the study were patients with AHF who were not treated with optimal doses of GDMT before and after discharge from an AHF admission. Data were analyzed from January to October 2023. Interventions: The mean percentage of the doses of 3 classes of HF medications (renin-angiotensin system inhibitors, ß-blockers, and mineralocorticoid receptor antagonists) relative to their optimal doses was computed. Patients were classified into 3 dose categories: low (<50%), medium (≥50% to <90%), and high (≥90%). Dose and dose group were included as a time-dependent covariate in Cox regression models, which were used to test whether outcomes differed by dose. Main Outcome Measures: Post hoc secondary analyses of postdischarge 180-day HF readmission or death and 90-day change in quality of life. Results: A total of 515 patients (mean [SD] age, 62.7 [13.4] years; 311 male [60.4%]) assigned high-intensity care were included in this analysis. At 2 weeks, 39 patients (7.6%) achieved low doses, 254 patients (49.3%) achieved medium doses, and 222 patients (43.1%) achieved high doses. Patients with lower blood pressure and more congestion were less likely to be uptitrated to optimal GDMT doses at week 2. As a continuous time-dependent covariate, an increase of 10% in the average percentage optimal dose was associated with a reduction in 180-day HF readmission or all-cause death (primary end point: adjusted hazard ratio [aHR], 0.89; 95% CI, 0.81-0.98; P = .01) and a decrease in 180-day all-cause mortality (aHR, 0.84; 95% CI, 0.73-0.95; P = .007). Quality of life at 90 days, measured by the EQ-5D visual analog scale, improved more in patients treated with higher doses of GDMT (mean difference, 0.10; 95% CI, -4.88 to 5.07 and 3.13; 95% CI, -1.98 to 8.24 points in the medium- and high-dose groups relative to the low-dose group, respectively; P = .07). Adverse events to day 90 occurred less frequently in participants with HIC who were prescribed higher GDMT doses at week 2. Conclusions and Relevance: Results of this post hoc analysis of the STRONG-HF randomized clinical trial show that, among patients randomly assigned to high-intensity care, achieving higher doses of HF GDMT 2 weeks after discharge was feasible and safe in most patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03412201.

Cost-effectiveness of NT-proBNP-supported screening of chronic heart failure in patients with or without type 2 diabetes in Austria and Switzerland.

BACKGROUND: Heart failure (HF) is a clinical syndrome with a global burden. Signs and symptoms of HF are nonspecific and often shared with other conditions. The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) serves as a useful biomarker for the diagnosis of HF not only in patients with acute symptoms but also in outpatients with an ambiguous clinical presentation. The aim of the analysis is to evaluate the cost-effectiveness of implementing NT-proBNP in the diagnostic algorithm in patients with/without type 2 diabetes mellitus (T2DM), compared with a diagnosis based primarily on clinical signs or symptoms from the perspective of the Austrian and Swiss healthcare system. METHODS: A time-discrete Markov model was developed to simulate the effect/improvement (lifetime-costs, quality-adjusted life-years [QALYs], and life-years [LYs]) due to an NT-proBNP screening in undetected HF patients. Undetected HF patients are included in the model according to a distribution of New York Heart Association (NYHA) classes. The model considers disease progression by transition of NYHA classes. Undetected patients may remain undetected or be detected with the help of NT-proBNP or symptoms. Patients with known HF exhibit a slower disease progression. The probability of dying is influenced by the respective NYHA class. Direct costs (2021 € or CHF) were derived from published sources. QALYs, LYs, and costs were discounted (3% p.a.). RESULTS: In the per-patient analysis (at age 60 over lifetime), the incremental cost-utility ratio (ICUR)/QALY of NT-proBNP vs. no screening was €3,042 for HF patients in Austria. Considering the total cohort of undetected HF patients (n = 9,377) with the corresponding age structure over a lifetime, the ICUR increases to €4,356. In Switzerland, the per-patient results show an ICUR of CHF 897. Considering the total cohort of undetected HF patients (n = 6,826) the ICUR amounts to CHF 4,513. If indirect costs are considered, NT-proBNP screening becomes the dominant strategy in both countries. CONCLUSION: Overall, the analysis concludes that screening with NT-proBNP is a highly cost-effective or cost-saving diagnostic option for patients with HF, and a sensitivity analysis confirmed these findings.

[Vaskuläre Dyspnoe: Lungenembolie]. / Vaskuläre Dyspnoe: Lungenembolie.

INTRODUCTION: In clinical practice, the differentiation of pulmonary embolism from other entities often remains difficult. Of utmost importance is the estimation of the pretest probability of the disease: predictive scoring systems and the use of clinical gestalt are equally useful tools. Exclusion or confirmation of the disease requires the rationale use of additional investigations (laboratory, imaging). In this article, we provide clinical engrams and outline our diagnostic algorithm. Based on the latest recommendations, we summarize the therapeutic approach for patients with pulmonary embolism. The importance of follow-up visits after the initial event is discussed in the last part. The assessment of risk factors promoting the development of venous thromboembolism is crucial for estimating the risk of recurrence. Excessive screening (thrombophilia testing or tumor investigations) are of minor relevance.

Early changes in renal function during rapid up-titration of guideline-directed medical therapy following an admission for acute heart failure.

AIM: 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. METHODS AND RESULTS: 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). CONCLUSIONS: 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.

Non-cardiac comorbidities and intensive up-titration of oral treatment in patients recently hospitalized for heart failure: Insights from the STRONG-HF trial.

AIMS: To assess the potential interaction between non-cardiac comorbidities (NCCs) and the efficacy and safety of high-intensity care (HIC) versus usual care (UC) in the STRONG-HF trial, including stable patients with improved but still elevated natriuretic peptides. METHODS AND RESULTS: In the trial, eight NCCs were reported: anaemia, diabetes, renal dysfunction, severe liver disease, chronic obstructive pulmonary disease/asthma, stroke/transient ischaemic attack, 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 heart failure (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 11.4%, respectively. Achievement of full doses of HF therapies at 90 and 180 days in the HIC was similar irrespective of NCC number. In HIC, the primary endpoint occurred in 10.0%, 16.6%, 13.6% and 26.2%, in those with 0, 1, 2 and ≥3 NCCs, respectively, as compared to 19.1%, 25.4%, 23.3% and 26.2% in UC (interaction-p = 0.80). The treatment benefit of HIC versus UC on the primary endpoint did not 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). CONCLUSIONS: In the STRONG-HF trial, NCCs neither limited the rapid up-titration of HF therapies, nor attenuated the benefit of HIC on the primary endpoint. In the context of a clinical trial, the benefit-risk ratio favours the rapid up-titration of HF therapies even in patients with multiple NCCs.

Sex-specific analysis of the rapid up-titration of guideline-directed medical therapies after a hospitalization for acute heart failure: Insights from the STRONG-HF trial.

AIMS: The aim of this study was to evaluate efficacy and safety of rapid up-titration of guideline-directed medical therapies (GDMT) in men and women hospitalized for acute heart failure (AHF). METHODS AND RESULTS: In STRONG-HF, AHF patients were randomized just prior to discharge to either usual care (UC) or a high-intensity care (HIC) strategy of GDMT up-titration. In these analyses, we compared the implementation, efficacy, and safety of the HIC strategy between men and women. In the randomized 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 heart failure readmission or death, occurred in 15.8% HIC women versus 23.5% women in the UC group (adjusted hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.40-1.13) and in 14.9% HIC men versus 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. CONCLUSION: The results of the current analyses suggest that a rapid up-titration of GDMT immediately after an AHF hospitalization can and should be implemented similarly in men and women, as it results in reduction of 180-day all-cause death or heart failure readmission, quality-of-life improvement in both men and women with a similar safety profile.

Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure in elderly patients: A sub-analysis of the STRONG-HF randomized clinical trial.

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.

NT-proBNP and high intensity care for acute heart failure: the STRONG-HF trial.

AIMS: STRONG-HF showed that rapid up-titration of guideline-recommended medical therapy (GRMT), in a high intensity care (HIC) strategy, was associated with better outcomes compared with usual care. The aim of this study was to assess the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and its changes early during up-titration. METHODS AND RESULTS: A total of 1077 patients hospitalized for acute heart failure (HF) and with a >10% NT-proBNP decrease from screening (i.e. admission) to randomization (i.e. pre-discharge), were included. Patients in HIC were stratified by further NT-proBNP changes, from randomization to 1 week later, as decreased (≥30%), stable (<30% decrease to ≤10% increase), or increased (>10%). The primary endpoint was 180-day HF readmission or death. The effect of HIC vs. usual care was independent of baseline NT-proBNP. Patients in the HIC group with stable or increased NT-proBNP were older, with more severe acute HF and worse renal and liver function. Per protocol, patients with increased NT-proBNP received more diuretics and were up-titrated more slowly during the first weeks after discharge. However, by 6 months, they reached 70.4% optimal GRMT doses, compared with 80.3% for those with NT-proBNP decrease. As a result, the primary endpoint at 60 and 90 days occurred in 8.3% and 11.1% of patients with increased NT-proBNP vs. 2.2% and 4.0% in those with decreased NT-proBNP (P = 0.039 and P = 0.045, respectively). However, no difference in outcome was found at 180 days (13.5% vs. 13.2%; P = 0.93). CONCLUSION: Among patients with acute HF enrolled in STRONG-HF, HIC reduced 180-day HF readmission or death regardless of baseline NT-proBNP. GRMT up-titration early post-discharge, utilizing increased NT-proBNP as guidance to increase diuretic therapy and reduce the GRMT up-titration rate, resulted in the same 180-day outcomes regardless of early post-discharge NT-proBNP change.