Prognostic implications of volume status assessed by blood volume analysis in ambulatory heart failure.

The prognostic implications of intravascular volume status assessed by blood volume analysis (BVA) in ambulatory heart failure (HF) remain uncertain. The incremental benefits of assessing volume status, beyond the well-established filling pressures, in predicting HF outcomes are unknown.

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.

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.

Impact of empagliflozin on decongestion in acute heart failure: the EMPULSE trial.

AIMS: Effective and safe decongestion remains a major goal for optimal management of patients with acute heart failure (AHF). The effects of the sodium-glucose cotransporter 2 inhibitor empagliflozin on decongestion-related endpoints in the EMPULSE trial (NCT0415775) were evaluated. METHODS AND RESULTS: A total of 530 patients hospitalized for AHF were randomized 1:1 to either empagliflozin 10 mg once daily or placebo for 90 days. The outcomes investigated were: weight loss (WL), WL adjusted for mean daily loop diuretic dose (WL-adjusted), area under the curve of change from baseline in N-terminal pro-B-type natriuretic peptide levels, hemoconcentration, and clinical congestion score after 15, 30, and 90 days of treatment. Compared with placebo, patients treated with empagliflozin demonstrated significantly greater reductions in all studied markers of decongestion at all time-points, adjusted mean differences (95% confidence interval) at Days 15, 30, and 90 were: for WL -1.97 (-2.86, -1.08), -1.74 (-2.73, -0.74); -1.53 (-2.75, -0.31) kg; for WL-adjusted: -2.31 (-3.77, -0.85), -2.79 (-5.03, -0.54), -3.18 (-6.08, -0.28) kg/40 mg furosemide i.v. or equivalent; respectively (all P < 0.05). Greater WL at Day 15 (i.e. above the median WL in the entire population) was associated with significantly higher probability for clinical benefit at Day 90 (hierarchical composite of all-cause death, heart failure events, and a 5-point or greater difference in Kansas City Cardiomyopathy Questionnaire total symptom score change from baseline to 90 days) with the win ratio of 1.75 (95% confidence interval 1.37, 2.23; P < 0.0001). CONCLUSION: Initiation of empagliflozin in patients hospitalized for AHF resulted in an early, effective and sustained decongestion which was associated with clinical benefit at Day 90.

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.

Effects of Empagliflozin on Symptoms, Physical Limitations, and Quality of Life in Patients Hospitalized for Acute Heart Failure: Results From the EMPULSE Trial.

BACKGROUND: Patients hospitalized for acute heart failure experience poor health status, including a high burden of symptoms and physical limitations, and poor quality of life. SGLT2 (sodium-glucose cotransporter 2) inhibitors improve health status in chronic heart failure, but their effect on these outcomes in acute heart failure is not well characterized. We investigated the effects of the SGLT2 inhibitor empagliflozin on symptoms, physical limitations, and quality of life, using the Kansas City Cardiomyopathy Questionnaire (KCCQ) in the EMPULSE trial (Empagliflozin in Patients Hospitalized With Acute Heart Failure Who Have Been Stabilized). METHODS: Patients hospitalized for acute heart failure were randomized to empagliflozin 10 mg daily or placebo for 90 days. The KCCQ was assessed at randomization and 15, 30, and 90 days. The effects of empagliflozin on the primary end point of clinical benefit (hierarchical composite of all-cause death, heart failure events, and a 5-point or greater difference in KCCQ Total Symptom Score [TSS] change from baseline to 90 days) were examined post hoc across the tertiles of baseline KCCQ-TSS. In prespecified analyses, changes (randomization to day 90) in KCCQ domains, including TSS, physical limitations, quality of life, clinical summary, and overall summary scores were evaluated using a repeated measures model. RESULTS: In total, 530 patients were randomized (265 each arm). Baseline KCCQ-TSS was low overall (mean [SD], 40.8 [24.0] points). Empagliflozin-treated patients experienced greater clinical benefit across the range of KCCQ-TSS, with no treatment effect heterogeneity (win ratio [95% CIs] from lowest to highest tertile: 1.49 [1.01-2.20], 1.37 [0.94-1.99], and 1.48 [1.00-2.20], respectively; P for interaction=0.94). Beneficial effects of empagliflozin on health status were observed as early as 15 days and persisted through 90 days, at which point empagliflozin-treated patients experienced a greater improvement in KCCQ TSS, physical limitations, quality of life, clinical summary, and overall summary (placebo-adjusted mean differences [95% CI]: 4.45 [95% CI, 0.32-8.59], P=0.03; 4.80 [95% CI, 0.00-9.61], P=0.05; 4.66 [95% CI, 0.32-9.01], P=0.04; 4.85 [95% CI, 0.77-8.92], P=0.02; and 4.40 points [95% CI, 0.33-8.48], P=0.03, respectively). CONCLUSIONS: Initiation of empagliflozin in patients hospitalized for acute heart failure produced clinical benefit regardless of the degree of symptomatic impairment at baseline, and improved symptoms, physical limitations, and quality of life, with benefits seen as early as 15 days and maintained through 90 days. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT0415775.

Relationship of Vascular Endothelial Growth Factor C, a Lymphangiogenesis Modulator, With Edema Formation, Congestion and Outcomes in Acute Heart Failure.

BACKGROUND: Although vascular endothelial growth factor C (VEGF-C) is a known lymphangiogenesis modulator, its relationship with congestion formation and outcomes in acute heart failure (AHF) is unknown. METHODS: Serum VEGF-C levels were measured in 237 patients hospitalized for AHF. The population was stratified by VEGF-C levels and linked with clinical signs of congestion and outcomes. RESULTS: The study's population was divided in VEGF-C tertiles: low (median [Q25-Q75]: 33 [15-175]), medium (606 [468-741]) and high (1141 [968-1442] pg/mL). The group with low VEGF-C on admission presented with the highest prevalence of severe lower-extremity edema (low VEGF-C vs medium VEGF-C vs high VEGF-C): 30% vs 13% vs 20%; P = 0.02); the highest percentage of patients with ascites: 22% vs 9% vs 6%; P = 0.006; and the lowest proportion of patients with pulmonary congestion: 22% vs 30% vs 46%; P = 0.004. The 1-year mortality rate was the highest in the low VEGF-C tertile: 35% vs 28% vs 18%, respectively; P = 0.049. The same pattern was observed for the composite endpoint (death and AHF rehospitalization): 45% vs 43% vs 26%; P = 0.029. The risks of death at 1-year follow-up and composite endpoint were significantly lower in the high VEGF-C group. CONCLUSIONS: Low VEGF-C was associated with more severe signs of congestion (signs of fluid accumulation) and adverse clinical outcomes.

Role of the Renal Lymphatic System in Heart Failure.

PURPOSE OF REVIEW: The lymphatic system plays a major but overlooked role in maintaining fluid homeostasis. Given the unique fluid homeostasis functions of the kidneys, dysregulation of the renal lymphatic system underlies the development of self-propagating congestive pathomechanisms. In this review, we outline the roles of the renal lymphatic system in heart failure (HF). RECENT FINDINGS: Studies have uncovered several pathomechanisms involving the renal lymphatic system in congestive states, such as impaired interstitial draining by the renal lymphatic system, impaired structure and valves of renal lymphatics, lymphatic-induced increase in renal reabsorption of water and sodium, and development of albuminuria with proteinuria-induced renal lymphangiogenesis. These self-propagating mechanisms result in "renal tamponade" with manifestations of cardiorenal syndrome and inappropriate renal response to diuretics. Dysregulation of the renal lymphatic system is integral to the development and progression of congestion in HF. Targeting renal lymphatics may provide a novel pathway to treat intractable congestion.

Pathophysiology and Treatment Opportunities of Iron Deficiency in Heart Failure: Is There a Need for Further Trials?

PURPOSE OF REVIEW: Iron deficiency (ID) complicates heart failure (HF) at different stages of the natural history of the disease; however, this frequent comorbidity is still not comprehensively understood and investigated in terms of pathophysiology. Intravenous iron therapy with ferric carboxymaltose (FCM) should be considered to improve the quality of life, exercise capacity, and symptoms in stable HF with ID, as well as to reduce HF hospitalizations in iron-deficient patients stabilized after an episode of acute HF. The therapy with intravenous iron, however, continues to generate important clinical questions for cardiologists. RECENT FINDINGS: In the current paper, we discuss the class effect concept for intravenous iron formulations beyond FCM, based on the experiences of nephrologists who administer different intravenous iron formulations in advanced chronic kidney disease complicated with ID and anemia. Furthermore, we discuss the neutral effects of oral iron therapy in patients with HF, because there are still some reasons to further explore this route of supplementation. The different definitions of ID applied in HF studies and new doubts regarding possible interactions of intravenous iron with sodium-glucose co-transporter type 2 inhibitors are also emphasized. The experiences of other medical specializations may provide new information on how to optimally replenish iron in patients with HF and ID.

Getting ahead of the game: in-hospital initiation of HFrEF therapies.

Hospitalizations for heart failure (HF) have become a global problem worldwide. Each episode of HF decompensation may lead to deleterious short- and long- term consequences, but on the other hand is an unique opportunity to adjust the heart failure pharmacotherapy. Thus, in-hospital and an early post-discharge period comprise an optimal timing for initiation and optimization of the comprehensive management of HF. This timeframe affords clinicians an opportunity to up titrate and adjust guideline-directed medical therapies (GDMT) to potentially mitigate poor outcomes associated post-discharge and longer-term. This review will cover this timely concept, present the data of utilization of GDMT in HF populations, discuss recent evidence for in-hospital initiation and up-titration of GDMT with a need for post-discharge follow-up and implementation this into clinical practice in patients with heart failure and reduced ejection fraction.

Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure.

AIMS: In healthy volunteers, the kidney deploys compensatory post-diuretic sodium reabsorption (CPDSR) following loop diuretic-induced natriuresis, minimizing sodium excretion and producing a neutral sodium balance. CPDSR is extrapolated to non-euvolemic populations as a diuretic resistance mechanism; however, its importance in acute decompensated heart failure (ADHF) is unknown. METHODS AND RESULTS: Patients with ADHF in the Mechanisms of Diuretic Resistance cohort receiving intravenous loop diuretics (462 administrations in 285 patients) underwent supervised urine collections entailing an immediate pre-diuretic spot urine sample, then 6-h (diuretic-induced natriuresis period) and 18-h (post-diuretic period) urine collections. The average spot urine sodium concentration immediately prior to diuretic administration [median 15 h (13-17) after last diuretic] was 64 ± 33 mmol/L with only 4% of patients having low (<20 mmol/L) urine sodium consistent with CPDSR. Paradoxically, greater 6-h diuretic-induced natriuresis was associated with larger 18-h post-diuretic spontaneous natriuresis (r = 0.7, P < 0.001). Higher pre-diuretic urine sodium to creatinine ratio (r = 0.37, P < 0.001) was the strongest predictor of post-diuretic spontaneous natriuresis. In a subgroup of patients (n = 43) randomized to protocol-driven intensified diuretic therapies, the mean diuretic-induced natriuresis increased three-fold. In contrast to the substantial decrease in spontaneous natriuresis predicted by CPDSR, no change in post-diuretic spontaneous natriuresis was observed (P = 0.47). CONCLUSION: On a population level, CPDSR was not an important driver of diuretic resistance in hypervolemic ADHF. Contrary to CPDSR, a greater diuretic-induced natriuresis predicted a larger post-diuretic spontaneous natriuresis. Basal sodium avidity, rather than diuretic-induced CPDSR, appears to be the predominant determinate of both diuretic-induced and post-diuretic natriuresis in hypervolemic ADHF.

Pathophysiology of Advanced Heart Failure: What Knowledge Is Needed for Clinical Management?

Understanding of heart failure (HF) has evolved from a simple hemodynamic problem through a neurohormonally and proinflammatory-driven syndrome to a complex multiorgan dysfunction accompanied by inadequate energy handling. This article discusses the most important clinical aspects of advanced HF pathophysiology. It presents the concept of neurohormonal activation and its deleterious effect on cardiovascular system and reflex control. The current theories regarding the role of inflammation, cytokine activation, and myocardial remodeling in HF progression are presented. Advanced HF is a multiorgan syndrome with interplay between cardiovascular system and other organs. The role of iron deficiency is also discussed.

Iron deficiency defined as depleted iron stores accompanied by unmet cellular iron requirements identifies patients at the highest risk of death after an episode of acute heart failure.

AIM: Acute heart failure (AHF) critically deranges haemodynamic and metabolic homoeostasis. Iron is a key micronutrient for homoeostasis maintenance. We hypothesized that iron deficiency (ID) defined as depleted iron stores accompanied by unmet cellular iron requirements would in this setting predict the poor outcome. METHODS AND RESULTS: Among 165 AHF patients (age 65 ± 12 years, 81% men, 31% de novo HF), for ID diagnosis we prospectively applied: low serum hepcidin reflecting depleted iron stores (<14.5 ng/mL, the 5th percentile in healthy peers), and high-serum soluble transferrin receptor (sTfR) reflecting unmet cellular iron requirements (≥1.59 mg/L, the 95th percentile in healthy peers). Concomitance of low hepcidin and high sTfR (the most profound ID) was found in 37%, isolated either high sTfR or low hepcidin was found in 29 and 9% of patients, and 25% of subjects demonstrated preserved iron status. Patients with low hepcidin and high sTfR had peripheral oedema, high NT-proBNP, high uric acid, low haemoglobin (P < 0.05), and 5% in-hospital mortality (0% in remaining patients). During the 12-month follow-up, 33 (20%) patients died. Those with low hepcidin and high sTfR had the highest 12-month mortality [(41% (95% CI: 29-53%)] when compared with those with isolated high sTfR [15% (5-25%)], isolated low hepcidin [7% (0-19%)] and preserved iron status (0%) (P < 0.001). Analogous mortality patterns were seen separately in anaemics and non-anaemics. CONCLUSION: Iron deficiency defined as depleted body iron stores and unmet cellular iron requirements is common in AHF, and identifies those with the poor outcome. Its correction may be an attractive therapeutic approach.

Emerging devices for heart failure management.

There have been significant advances in the treatment of heart failure (HF) in recent years, driven by significant strides in guideline-directed medical therapy (GDMT). Despite this, HF is still associated with high levels of morbidity and mortality, and most patients do not receive optimal medical therapy. In conjunction with the improvement of GDMT, novel device therapies have been developed to better treat HF. These devices include technology capable of remotely monitoring HF physiology, devices that modulate the autonomic nervous system, and those that structurally change the heart with the ultimate aim of addressing the root causes of HF physiology As these device therapies gradually integrate into the fabric of HF patient care, it becomes increasingly important for modern cardiologists to become familiar with them. Hence, the objective of this review is to shed light on currently emerging devices for the treatment of HF.

Empagliflozin in the treatment of heart failure.

Heart failure (HF) affects more than 60 million individuals globally. Empagliflozin is currently approved for type 2 diabetes and chronic HF. Clinical trials have demonstrated that empagliflozin reduces the composite end point of hospitalizations for HF and mortality and improves the quality of life irrespective of left ventricular ejection fraction. Empagliflozin is a once-daily medication with minimal drug-drug interactions and does not require titration. Empagliflozin causes mild weight loss and does not significantly reduce blood pressure. Empagliflozin acts as an enabler for other HF drugs by reducing the risk of hyperkalemia. Empagliflozin is also beneficial for chronic kidney disease which exists commonly with HF. This review outlines the pharmacokinetics, pharmacodynamics, safety, and efficacy of empagliflozin in HF across various sub-groups and settings.

Empagliflozin is a one-daily medication and is an effective glucose-lowering drug for the treatment of diabetes. In recent years, researchers and medical professionals have discovered that empagliflozin may also be used to treat some cardiovascular conditions. Numerous people suffer from myocardial infarction ('heart attack') each year. According to several clinical trials, empagliflozin may slow the course of myocardial infarction and improve clinical outcomes and quality of life. Additionally, empagliflozin does not result in a substantial decrease in blood pressure and can also lead to mild weight loss. Therefore, empagliflozin shows potential as a useful medication for the treatment of myocardial infarction, especially in individuals with diabetes and impaired kidney function.

Spot urine sodium-to-creatinine ratio surpasses sodium in identifying poor diuretic response in acute heart failure.

AIMS: We aim to identify the most accurate marker for early prediction of poor diuretic response in acute heart failure (AHF) patients with signs of congestion requiring intravenous diuretic treatment. METHODS: In this single-centre, prospective observational study, AHF patients with signs of congestion received a standardized intravenous furosemide dose (1 mg/kg of body weight; 40 mg in bolus and remaining dose in 2 h continuous infusion). Subsequently, we assessed spot urine composition at 2 h post-administration, comparing it with total urine output at 6 h. Various potential urine markers were analysed for predicting urine output using receiver operating characteristic (ROC) curves and logistic regression models. We investigated guideline-recommended markers, including spot urine sodium (UNa+) and its cut-off, and introduced the UNa+/UCr (urine creatinine concentration) ratio adjusting UNa+ for urine dilution. RESULTS: Out of 111 patients (85% males, 66.4 ± 13.9 years old, NTproBNP 7290 [4493-14 582] pg/ml), there were 18 (16%) with a poor diuretic response (cumulative urine output <600 ml during the first 6 h). The mean 6 h cumulative diuresis in patients with poor and good diuretic response was 406 ± 142 and 2114 ± 1164 ml, respectively, P < 0.005. After an initial evaluation of several potential biomarkers, only UNa+, UCr and UNa+/UCr were selected as candidates with the highest predictive value. The cut-off for UNa+ adjusted for urine dilution: UNa+/UCr ratio <0.167 mmol/mg × 10-1 was determined by ROC analysis with the highest area under the curve (95% confidence interval): 0.956 (0.915-0.997), P < 0.001. When compared with the guideline-recommended cut-off (UNa+ <50 mmol/L as a reference, specificity-0.97; sensitivity-0.83), the odds ratio (OR) for UNa+/UCreat to identify a poor diuretic response was 2.5 times greater, regardless of kidney function (OR for estimated glomerular filtration rate in the logistic regression model was 0.978 [0.945-1.013, P = 0.222]). CONCLUSIONS: The UNa+/UCr ratio in a spot urine sample 2 h after intravenous diuretic administration is a simple, highly predictive marker for the identification of AHF patients with poor diuretic response, surpassing guidelines-recommended markers like UNa+.

Prevalence of increased intra-abdominal pressure and its impact on renal function in acute decompensated heart failure: A prospective pilot study.

BACKGROUND: Intra-abdominal pressure (IAP) is a frequently overlooked aspect in clinical assessment that can have a significant impact on organ dysfunction in patients with acute decompensated heart failure (ADHF). AIMS: We aimed to investigate dynamics of IAP in patients with ADHF and its impact on diuretic response. METHODS: We conducted a prospective observational pilot study on a group consisting of 30 patients admitted for ADHF. In every individual IAP measurement, blood and urine samples were taken upon admission, on the second and third days of hospitalization. RESULTS: The study showed a high (63.3%) prevalence of intra-abdominal hypertension (IAH) defined as IAP ≥12 mm Hg upon admission, while only roughly 13% had signs of ascites. We observed poorer diuresis on the first day of hospitalization in the IAH group (P = 0.03). IAP was negatively correlated with urine output (P = 0.01) and positively correlated with urine osmolality (P = 0.03) on the first day of hospitalization. During follow-up, there was a significant decrease in IAP in patients with IAH upon admission who received standard decongestive therapy. CONCLUSIONS: The study shows a high prevalence of IAH in patients admitted for ADHF, even in individuals who do not present symptoms of abdominal congestion. Established correlation between IAP, reduced diuresis, and increased urine osmolality, despite achieving target natriuresis, contributes novel insights into the understanding of pathomechanisms underlying diuretic resistance in ADHF.

The role of urine chloride in acute heart failure.

In our retrospective study, we aimed to investigate the relationship between urinary chloride (uCl-) and selected clinical and laboratory biomarkers, renal function, and patient outcomes in the acute heart failure (AHF) population. We divided 248 adult patients (≥ 18 years) with AHF into two groups: low uCl- (< 115 mmol/L) and high uCl-. The mean age of the patient group was 70.2 ± 12.6, and 182 patients were male (73.4%). Clinical endpoints included in-hospital mortality, one-year mortality, and a composite endpoint of one-year mortality and rehospitalization for heart failure. Patients were followed up for at least one year. Relevant clinical and baseline biomarker data were collected, including markers concerning inflammation, liver and kidney function, perfusion and congestion, iron status, cardiac remodeling, gasometry, renin and aldosterone. Low uCl- was associated with worse in-hospital outcomes, including higher in-hospital mortality (7.7% vs. 1.4%, p = 0.014), the need for inotropic support (20.19% vs. 2.08%, p ≤ 0.001), worsening of HF during therapy (17.31% vs. 4.86%, p ≤ 0.001), and the need for treatment in an intensive cardiac care unit (33.65% vs. 15.28%, p ≤ 0.001). Low uCl- was a significant predictor of one-year mortality (40.4% vs. 16.7%, p < 0.05) and the composite outcome (HR 2.42, 95% CI 1.43-4.08, p < 0.001). In the multivariable analysis, uCl- was independently associated with the risk of one-year mortality (HR 0.92, 95% CI 0.87-0.98, p < 0.05) and the composite outcome (HR 0.95, 95% CI 0.92-0.99, p < 0.05). Our findings suggest that low uCl- is a marker of more advanced heart failure, activation of the renin-angiotensin-aldosterone system and is related to worse one-year outcomes.