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.

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.

Proportional pulse pressure relates to cardiac index in stabilized acute heart failure patients.

AIMS: In chronic heart failure, proportional pulse pressure (PPP) is suggested as an estimate of cardiac index (CI). The association between CI and PPP in acute heart failure (AHF) has not been described. METHODS: This was examined using hemodynamic measurements (from a trial using serelaxin) in 63 stabilized AHF patients. RESULTS: Mean (SD) age was 68 (11), 74% male, mean (SD) ejection fraction (EF) was 33.4% (13.7), mean (SD) CI (L/min/m2) was 2.3 (0.6). CI correlated with PPP (Pearson R = 0.42; p < 0.0001) based on a linear mixed-effects model analysis of 171 pairs of measurements from 47 patients (out of 63) where CI and PPP were measured within 3 min of each other during. Serelaxin treatment did not modify the established correlation between CI and PPP. Time-weighted average CI correlated with time-weighted average PPP (Spearman Rank R = 0.35; p = 0.0051) over the -4 h to 24 h time interval. In a multivariable regression analysis, low PPP was an independent predictor of low CI (p < 0.0001). CONCLUSIONS: In patients with AHF after initial clinical stabilization, both baseline and post-baseline CI measurements are positively related to PPP. This was the most closely related non-invasive blood pressure variable to CI.

A randomized, double-blind, placebo-controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failure.

AIMS: The aim of this study was to evaluate the haemodynamic effects of serelaxin (30 µg/kg/day 20-h infusion and 4-h post-infusion period) in patients with acute heart failure (AHF). METHODS AND RESULTS: This double-blind, multicentre study randomized 71 AHF patients with pulmonary capillary wedge pressure (PCWP) ≥ 18 mmHg, systolic blood pressure (BP) ≥ 115 mmHg, and estimated glomerular filtration rate ≥ 30 mL/min/1.73 m(2) to serelaxin (n = 34) or placebo (n = 37) within 48 h of hospitalization. Co-primary endpoints were peak change from baseline in PCWP and cardiac index (CI) during the first 8 h of infusion. Among 63 patients eligible for haemodynamic analysis (serelaxin, n = 32; placebo, n = 31), those treated with serelaxin had a significantly higher decrease in peak PCWP during the first 8 h of infusion (difference vs. placebo: -2.44 mmHg, P = 0.004). Serelaxin showed no significant effect on the peak change in CI vs. placebo. Among secondary haemodynamic endpoints, a highly significant reduction in pulmonary artery pressure (PAP) was observed throughout the serelaxin infusion (largest difference in mean PAP vs. placebo: -5.17 mmHg at 4 h, P < 0.0001). Right atrial pressure, systemic/pulmonary vascular resistance, and systolic/diastolic BP decreased from baseline with serelaxin vs. placebo and treatment differences reached statistical significance at some time points. Serelaxin administration improved renal function and decreased N-terminal pro-brain natriuretic peptide levels vs. placebo. Treatment with serelaxin was well tolerated with no apparent safety concerns. CONCLUSION: The haemodynamic effects of serelaxin observed in the present study provide plausible mechanistic support for improvement in signs and symptoms of congestion observed with this agent in AHF patients. ClinicalTrials.gov identifier NCT01543854.

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.

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.

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+.

Spot urine sodium as a marker of urine dilution and decongestive abilities in acute heart failure.

The decongestion ability in response to diuretic treatment plays a crucial role in the treatment of acute heart failure. This effectiveness is evaluated through the assessment of sodium concentration and urine volume, which are also treatment goals themselves. However, the bidirectional interconnection between these factors remains not fully understood. The objective of this study is to provide mechanistic insights into the correlation between spot urine sodium concentrations (UNa+) and urine dilution. This aims to better understand of the decongestive abilities in acute heart failure (AHF). The study was single-center, prospective, conducted on a group of 50 AHF patients. Each participant received a standardized furosemide dose of 1 mg per kg of body weight. Hourly diuresis was measured in the first 6 h of the study, and urine composition was assessed at predefined timepoints. The study group presented the exponential (rather than linear) pattern of relationship between UNa+ and 6-h urine volume, whereas relationship between eGFR and 6-h urine volume was linear (r = 0.61, p < 0.001). The relationship between UNa+ and all other analyzed indices of urine dilution, including the change from baseline in urine creatinine concentration, urine osmolarity, and urine osmolarity corrected for urine sodium, also exhibited an exponential relationship. Patients who were chronically exposed to furosemide demonstrated a significantly lower urine dilution (1.78 [1.18-3.54] vs 11.58 [3.9-17.88]; p < 0.001) in comparison to naïve individuals. In conclusion, it should be noted that in AHF higher UNa+ is associated with disproportionally higher urine dilution, and patients naïve to furosemide have significantly greater ability to dilute urine when compare to chronic furosemide users.

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.

The early safety profile of simultaneous vaccination against influenza and Respiratory Syncytial Virus (RSV) in patients with high-risk heart failure.

The safety of simultaneous vaccination for Respiratory Syncytial Virus (RSV) and influenza in vulnerable high-risk heart failure (HF) patients remains unclear. In an open-label, prospective study, 105 patients received concurrent influenza (Vaxigrip Tetra, season 2023/2024, Sanofi) and RSV (Arexvy, GSK) vaccinations from September 15th to November 17th, 2023. Adverse events were collected on the fourth-day post-vaccination. Overall, the vaccination was well tolerated, with the most common reaction being injection site pain (63 %). General symptoms occurred in 33 % of patients, predominantly fatigue (23 %), myalgia (12 %), and headache (9 %). Grade 3 reactions were observed in 6 % of patients, and a few experienced temperature elevation or flu-like symptoms, managing them with antipyretics. Notably, there were no exacerbations of HF, hospitalizations, or deaths within a week post-vaccination. This study indicates the safety of simultaneous influenza and RSV vaccination in high-risk HF patients, with a low incidence of mild adverse events.

Lower Extremity Lymphatic Flow/Drainage Assessment by Indocyanine Green Fluorescent Lymphography in Heart Failure Patients.

The purpose of this study was to present a protocol for visualizing lymphatic flow in patients with heart failure (HF) by using indocyanine green fluorescence lymphography. We studied 37 subjects: 20 patients with acute heart failure (AHF) and lower limb edema, 7 patients with chronic heart failure (CHF) without lower limb edema, and 10 control subjects (no HF, no limb edema). All subjects were assessed at rest, and 11 subjects (6 control and 5 with CHF) were assessed again after a 10-minute walk. The lymph flow was visualized in all selected patients without complications. At rest, there was either no lymph flow or minimal lymph flow in all control subjects and patients with CHF, whereas the majority of patients with AHF demonstrated significant lymph flow. This study describes a new method to visualize/assess lymphatic flow in patients with HF, allowing for continuous, real-time tracking of lymphatic flow in the lower extremity.

Effectiveness of remote pulmonary artery pressure estimating in heart failure: systematic review and meta-analysis.

Heart failure (HF) poses a significant challenge, often leading to frequent hospitalizations and compromised quality of life. Continuous pulmonary artery pressure (PAP) monitoring offers a surrogate for congestion status in ambulatory HF care. This meta-analysis examines the efficacy of PAP monitoring devices (CardioMEMS and Chronicle) in preventing adverse outcomes in HF patients, addressing gaps in prior randomized controlled trials (RCTs). Five RCTs (2572 participants) were systematically reviewed. PAP monitoring significantly reduced HF-related hospitalizations (RR 0.72 [95% CI 0.6-0.87], p = 0.0006) and HF events (RR 0.86 [95% CI 0.75-0.99], p = 0.03), with no impact on all-cause or cardiovascular mortality. Subgroup analyses highlighted the significance of CardioMEMS and blinded studies. Meta-regression indicated a correlation between prolonged follow-up and increased reduction in HF hospitalizations. The risk of bias was generally high, with evidence certainty ranging from low to moderate. PAP monitoring devices exhibit promise in diminishing HF hospitalizations and events, especially in CardioMEMS and blinded studies. However, their influence on mortality remains inconclusive. Further research, considering diverse patient populations and intervention strategies with extended follow-up, is crucial for elucidating the optimal role of PAP monitoring in HF management.

Renal Assessment in Acute Cardiorenal Syndrome.

Cardiorenal syndrome (CRS) is a complex, heterogeneous spectrum of symptoms that has kept cardiologists awake for decades. The heart failure (HF) population being burdened with multimorbidity poses diagnostic and therapeutic challenges even for experienced clinicians. Adding deteriorated renal function to the equation, which is one of the strongest predictors of adverse outcome, we measure ourselves against possibly the biggest problem in modern cardiology. With the rapid development of new renal assessment methods, we can treat CRS more effectively than ever. The presented review focuses on explaining the pathophysiology, recent advances and current practices of monitoring renal function in patients with acute CRS. Understanding the dynamic interaction between the heart and the kidney may improve patient care and support the selection of an effective and nephroprotective treatment strategy.

Timing of decongestion and its impact on acute heart failure prognosis.

Introduction: The risk of unfavourable outcomes after an acute heart failure (AHF) episode remains high. Effective decongestion, reflected by haemoconcentration (HC), may guide therapy. Optimal timing of HC remains unspecified. Methods: We analysed the AHF registry to evaluate the prognostic differences of various timing of HC. Subjects were divided into 3 groups by time of reaching HC. Results: The groups differed in terms of 1-year occurrence of a composite of the mortality and AHF hospitalization (26% vs. 46% vs. 40%, early vs. late vs. no HC, p = 0.016). Conclusions: Patients reaching HC earlier seem to present the best prognosis regarding the analysed composite endpoint.

Diuretic, natriuretic, and chloride-regaining effects of oral acetazolamide as an add-on therapy for acute heart failure with volume overload: a single-center, prospective, randomized study.

INTRODUCTION: Decongestion is a therapeutic target in acute heart failure (AHF). Acetazolamide is a diuretic that decreases proximal tubular sodium reabsorption, and may also reverse hypochloremia Objectives: We assessed the decongestive, natriuretic, and chloride­regaining effects as well as the renal safety profile of oral acetazolamide (250 mg) used as an add­on therapy in patients with AHF. PATIENTS AND METHODS: This prospective, randomized study was conducted at the Institute of Heart Diseases in Wroclaw, Poland. It involved patients with AHF who were randomly assigned to receive either 250 mg of oral acetazolamide or standard care, and who underwent clinical and laboratory follow­up for 3 consecutive days since the beginning of the treatment and at discharge. RESULTS: The study population comprised 61 patients (71% men), of whom 31 (51%) were included in the acetazolamide group. The mean (SD) age of the patients was 68 (13) years. In comparison with the controls, the acetazolamide group demonstrated significantly higher cumulative diuresis after 48 and 72 hours since treatment implementation, negative fluid balance, weight loss after 48 hours of treatment, weight loss throughout the hospitalization, natriuresis, and serum chloride concentration. In terms of the renal safety profile, no increase in the creatinine concentration and urinary renal biomarker levels was noted. CONCLUSIONS: Oral acetazolamide seems to be a valuable add­on therapy that helps achieve comprehensive decongestion in patients with AHF.

Prognostic significance and clinical determinants of residual dyspnoea at discharge in acute heart failure: a single-centre, prospective observational study.

OBJECTIVE: This study aimed to assess the prognostic significance of residual (discharge) dyspnoea in acute heart failure (AHF) patients. DESIGN: Single-centre, prospective observational study. SETTING: Patients hospitalised for decompensated AHF in a single cardiology centre, in Poland. PARTICIPANTS: All patients (n=202) who survived the hospitalisation with the primary diagnosis of AHF and were discharged from the hospital. PRIMARY AND SECONDARY OUTCOME MEASURES: 1-year all-cause mortality; and the composite endpoint of 1-year all-cause mortality and rehospitalisation for the HF (whichever occurred first). RESULTS: On admission, 159 (78.7%) AHF patients presented dyspnoea at rest, while residual resting dyspnoea at discharge was present in 16 patients (7.9%). There were 48 (24%) patients with moderate/severe exertional dyspnoea at discharge. In the multivariable model, the resting dyspnoea at discharge was related to a higher risk of both 1-year mortality and composite outcome, with HR (95% CI) 8.0 (3.7 to 17.3) and 5.1 (2.6 to 10.2), respectively, both p<0.0001. Analogically, moderate or severe residual dyspnoea at discharge was related to the heightened risk of study both outcomes, with HR (95% CI) 3.1 (1.8 to 5.4) and 1.8 (1.1 to 2.9), respectively, p<0.01. CONCLUSIONS: Among AHF patients the residual dyspnoea at discharge was unexpectedly common and was associated with an unfavourable outcome during 1-year follow-up.

Impact of assisted exercises on skeletal muscle oxygenation levels in men with acutely decompensated heart failure.

BACKGROUND: The complex clinical status of modern day patients hospitalized due to acute heart failure (AHF) results from their advanced age, comorbidities, frailty, heart failure symptoms (including massive swelling of the lower limb), and dramatic reduction of exercise tolerance. Hence, there is a need to implement physiotherapeutic procedures as early as possible, aiming to both accelerate the restoration of clinical stabilization and prevent post-hospital disability. OBJECTIVES: We investigated whether assisted lower limb exercises have an impact on perfusion and oxygenation in skeletal muscle and if they are feasible in patients with AHF. MATERIAL AND METHODS: We examined 34 men (age: 66 ±11 years; left ventricular ejection fraction (LVEF): 34 ±11%; clinical presentation: 31 wet-warm and 3 wet-cold). The intervention (carried out on the 2nd day of hospitalization) included: 1) a 3-minute rest period; 2) an exercise phase (45 repetitions of assisted flexion and extension of the lower limb; and 3) a 10-minute relaxation period. We analyzed blood pressure (BP), heart rate (HR), respiratory rate (RR), tissue oxygenation (reflected by oxygen saturation measured with a pulse oximeter), and changes in peripheral tissue perfusion (reflected by the tissue oxygenation index (TOI) measured with near-infrared spectroscopy (NIRS)). RESULTS: The hemodynamic parameters (both ΔHR and Δsystolic BP) and oxygen saturation did not change (all p > 0.05), whereas the RR declined (p < 0.001). The exercises improved venous outflow (reflected by decreased oxygenated, deoxygenated and total hemoglobin, all p < 0.05) and increased peripheral tissue perfusion, as reflected by the TOI (p < 0.05). The patients reported relief and lack of dyspnea during and after the assisted exercises. CONCLUSIONS: The physiotherapeutic intervention improved both venous outflow and muscle oxygenation in men with AHF. The presented protocol was safe, feasible and well-tolerated, and resulted in relief for the patients. We believe that such procedures might be recommended for the initial period of rehabilitation in this challenging subgroup of patients.

Safety, Feasibility of Controllable Decrease of Vena Cava Pressure by Doraya Catheter in Heart Failure.

Lowering elevated central venous pressure may reduce renal dysfunction in acute heart failure (AHF) patients. The Doraya catheter lowers renal venous pressure by creating a gradient in the inferior vena cava below the renal veins. Here, we present a first-in-human feasibility study of the Doraya catheter performed on 9 AHF patients. We assessed the safety, feasibility, and acute clinical (hemodynamic and renal) effects of transient Doraya catheter deployment when added to the standard diuretic-based regimen in AHF patients with a poor diuretic response. The procedures decreased central venous pressure from 18.4 ± 3.8 mm Hg to 12.4 ± 4.7 mm Hg (P < 0.001) and improved mean diuresis and clinical signs of congestion. No device-related serious adverse events were observed. Thus, Doraya catheter deployment was safe and feasible in AHF patients. (First In Human Study of the Doraya Catheter for the Treatment of AHF Patients; NCT03234647).