Unplanned admissions for worsening heart failure (WHF) are the largest resource cost in heart failure (HF) management. Despite advances in pharmacological agents and interventional therapy, HF remains a global epidemic. One crucial-and costly-gap in HF management is the inability to obtain objective information to identify and quantify congestion and personalize treatment plans to effectively manage WHF events without resorting to expensive, invasive methods. Although the causes of WHF are varied and complex, the universal effect of HF decompensation is the significant decline in quality of life due to symptoms of hypervolemic congestion and the resultant reduction in cardiac output, which can be quantified via increased pulmonary venous congestion due to high intracardiac filling pressures. Accessible and reliable markers of congestion could more precisely quantify the severity of WHF events and stabilize patients earlier by interrupting and reversing this process with timely introduction or modification of evidence-based treatments. Pulmonary artery and cardiac pressure sensing tools have gained evidential credence and increased clinical uptake in recent years for the prevention and treatment of WHF, as studies of implantable hemodynamic devices have iteratively and reliably demonstrated substantial reductions in WHF events. Recent advances in sensing technologies have ranged from single-parameter invasive pulmonary artery monitors to completely non-invasive multi-parameter devices incorporating multi-sensor concept technologies aided by machine learning or artificial intelligence, although many remain investigational. This review aims to evaluate the potential for novel pulmonary artery and cardiac pressure sensing technology to reshape the management of WHF from within the hospitalized and ambulatory care environments.

Heart failure (HF) is a leading cause of hospitalizations, with over 1 million admissions annually in the USA and Europe due to signs and symptoms of congestion. Congestion in HF is now understood to result from both an absolute increase in total body fluid volume and a relative redistribution of fluid from capacitance vessels to the effective circulation. While guideline-directed medical therapy (GDMT) has greatly improved the outlook for stable HF patients, there has been little progress in managing acute HF (AHF) over the past 50 years. To address this unmet need, a group of expert clinicians met at the 63rd Annual Romanian Society of Cardiology Meeting on September 20th, 2024. They critically evaluated current evidence and identified knowledge gaps in three key areas of AHF management: (1) enhancing diuresis beyond standard therapy; (2) targeting fluid redistribution with intravenous vasodilators; and (3) applying hemodynamic profiling for personalized care. The first part of the discussion centered on enhanced diuresis strategies, covering contemporary real-world practice patterns, the relationship between residual congestion and hospital readmissions, findings from clinical trials of diuretic strategies, and recent insights into the role of GDMT in the acute setting. The panel also highlighted the limitations of existing evidence and proposed a research roadmap to optimize diuretic strategies in conjunction with GDMT in AHF, with the ultimate goal of facilitating decongestion in order to restore euvolemia and improve post-discharge outcomes.

Cardiorenal syndrome (CRS) is a challenging condition characterised by interdependent dysfunction of the heart and kidneys. Despite advancements in understanding its pathophysiology, clinical management remains complex due to overlapping mechanisms and high rates of diuretic resistance. Relevant literature was identified through a comprehensive narrative review of PubMed, Embase, and Cochrane Library databases, focusing on pivotal trials relating to CRS from 2005 to 2024. This review aims to provide a pragmatic, evidence-based approach to acute CRS management by addressing common misconceptions, outlining diagnostic strategies, and proposing a structured algorithm to manage diuretic resistance. We discuss the role of thoracic and venous excess ultrasound (VeXUS) in providing reliable measures of systemic congestion, natriuresis-guided sequential nephron blockade, and more targeted therapies, including ultrafiltration in refractory cases. In addition, we explore emerging trials that target renal hypoperfusion and venous congestion in CRS. Designed for a broad audience, including general physicians, cardiologists, and nephrologists, this review integrates clinical evidence with practical guidance to support effective and timely decision-making in the care of patients with CRS.

The use of circulatory assist devices has been shown to improve glomerular filtration rate and reduce the incidence of acute kidney injury in patients following acute cardiac pathology. However, the mechanisms of improvement in kidney function are not clear. We tested the hypothesis that mechanical circulatory support would result in a decrease in directly recorded renal sympathetic nerve activity (RSNA) and mediate the improvement in renal blood flow (RBF) in a setting of acute myocardial infarction (AMI)-induced left ventricular systolic dysfunction.

An anaesthetized ovine model was used to induce AMI (n = 8) using injections of microspheres into the left coronary artery in one group. The second group did not undergo embolization (n = 6). The effects of mechanical circulatory support using the Impella CP on directly recorded renal sympathetic nerve activity were examined in these two groups of animals.

Injection of microspheres resulted in a drop in mean arterial pressure (MAP) of 21 ± 4 mmHg compared to baseline values (p < 0.05; n = 8). This was associated with a 67% increase in renal sympathetic nerve activity (RSNA; from 16 ± 5 to 21 ± 5 spikes/s; p < 0.05; n = 7). Impella CP support significantly increased MAP by 13 ± 1.5 mmHg at pump level 8 (p < 0.05) in the AMI group. Incremental pump support resulted in a significant decrease in RSNA (p < 0.05) in both groups. At pump level P8 in the AMI group, RSNA was decreased by 21 ± 5.5% compared to pump level P0 when the pump was not on.

Our data indicate that the improvement in kidney function following mechanical circulatory support may be mediated in part by renal sympathoinhibition.

Congestion is a key clinical feature of heart failure (HF), contributing to hospitalizations, disease progression, and poor outcomes. While traditionally considered a hemodynamic issue, congestion is now recognized as a systemic process affecting multiple organs. Renal dysfunction arises from impaired perfusion and sodium retention, leading to maladaptive left ventricular remodeling. Hepatic congestion contributes to cholestatic liver injury, while metabolic disturbances drive anemia, muscle wasting, and systemic inflammation. Additionally, congestion disrupts the intestinal barrier and immune function, exacerbating HF progression. Given its widespread impact, effective congestion management requires a shift from a cardiovascular-centered approach to a comprehensive, multidisciplinary strategy. Targeted decongestive therapy, metabolic and nutritional optimization, and immune modulation are crucial in mitigating congestion-related organ dysfunction. Early recognition and intervention are essential to slow disease progression, preserve functional capacity, and improve survival. Addressing HF congestion through personalized, evidence-based strategies is vital for optimizing long-term care and advancing treatment paradigms.

Heart failure (HF) is a complex and debilitating syndrome that affects millions of people worldwide. In addition to the syndrome-related functional limitations, such as exercise intolerance and dyspnea, patients frequently suffer from various comorbidities. Neuropsychiatric conditions, including autonomic dysfunction, cognitive impairment, and depression, are important albeit underrecognized comorbidities in HF. Autonomic dysfunction, which is expressed as sympathetic predominance and decreased parasympathetic tone, is a key contributor to HF progression. Depression and cognitive impairment are highly prevalent in HF patients, affecting adherence to medical treatment and increasing morbidity and mortality risk. Stress cardiomyopathy, a usually reversible form of left ventricular dysfunction triggered by emotional or physical stress, is another clinical manifestation of the interplay between the heart and the brain. Early recognition and management of these comorbidities in HF patients are crucial for improving outcomes. This narrative review provides an overview of the pathophysiological mechanisms linking HF and brain disorders and discusses clinical perspectives of heart-brain interactions in the context of HF.

The intricate role of the autonomic nervous system (ANS) in regulating cardiac physiology has long been recognized. Aberrant function of the ANS is central to the pathophysiology of cardiovascular diseases. It stands to reason, therefore, that neuroscience-based cardiovascular therapeutics hold great promise in the treatment of cardiovascular diseases in humans. A decade after the inaugural edition, this White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology and pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases.

Intrarenal vein flow (IRVF) abnormalities can predict cardiovascular events including heart failure. This study aimed to evaluate the utility of short IRVF scans during routine comprehensive transthoracic echocardiography (TTE) examinations in a standard TTE laboratory.

We screened consecutive patients who underwent elective TTE at our Ultrasound Imaging Laboratory between March 2018 and July 2019 and prospectively enrolled those who completed a 5 min IRVF scan during the 30 min TTE procedure.

Among the 2101 screened patients, 1326 were included in the study cohort (age: 73 ± 13 years, 756 men). IRVF abnormalities were detected in 13 (1.0%) patients. Twenty-one cardiac events were observed (1.6%, 21/1326): one myocardial infarction and 20 heart failures. Cumulative survival probability plots were generated using the Kaplan-Meier method within 6 months after the TTE index day and assessed using the log-rank test. The plots revealed significantly worse prognoses in patients with elevated right arterial pressure (RAP) and abnormal IRVF, when compared to normal RAP or normal IEVF (p < 0.0001 and p < 0.0001, respectively). In a receiver operating curve analysis to predict the occurrence of cardiovascular events, E/e' had moderate predictive potential (area under the curve: 0.795, p < 0.0001), and the combination of E/e' and IRVF abnormality had better predictive potential than did E/e' alone (p = 0.043).

Although rarely observed on TTE, IRVF abnormalities improve the ability of E/e' to detect cardiac events, especially heart failure. Further large-scale prospective studies are required to confirm our findings.

The pathogenesis of heart failure with preserved ejection fraction (HFpEF) remains unclear, and effective treatments are limited. HFpEF is more prevalent in females, indicating potential gender differences in its pathogenesis. However, no female HFpEF model animals have been established. Hypertension is a major contributor to HFpEF, and sympathetic activation is thought to play a role in both conditions. This study aimed to establish a female HFpEF model using hypertensive Dahl salt-sensitive rats and to assess the presence of sympathetic activation. Seven-week-old female Dahl salt-sensitive rats were fed an 8% high-salt diet (HS group, n = 6), while a low-salt diet group (LS group, n = 9) served as controls. The HS group exhibited increased systolic blood pressure and heart rate. Echocardiography revealed an increased left ventricular (LV) wall thickness, a decreased E/A ratio, and an increased E/e' ratio, all indicative of diastolic dysfunction without reduced LV ejection fraction. Additionally, the HS group showed elevated LV end-diastolic pressure, LV weight, and lung weight, along with histological cardiomyocyte hypertrophy and interstitial fibrosis. Gene expression markers for cardiac hypertrophy and fibrosis were also increased. Renal function was significantly impaired, and plasma norepinephrine levels were elevated, consistent with heightened pre-sympathetic neuronal activity in the brain. In conclusion, high salt loading from 7 weeks of age in female Dahl salt-sensitive rats induced hypertensive HFpEF phenotypes with LV hypertrophy and fibrosis, and sympathetic activation by 16 to 19 weeks of age. This model provides a valuable tool for studying HFpEF pathophysiology in women.

This article discusses a tailored approach to managing cardiogenic shock and temporary mechanical circulatory support (tMCS). We also outline specific mobilization strategies for patients with different tMCS devices and configurations, which can be enabled by this tailored approach to cardiogenic shock management.

Safe and effective mobilization of patients with cardiogenic shock receiving tMCS can be accomplished. Appropriate patient selection, tailored device management, and dynamic multidisciplinary approaches to mobilization are critical to success. Cardiogenic shock is a heterogeneous condition characterized by end-organ dysfunction due to hypoperfusion and low cardiac output. Temporary mechanical circulatory support (tMCS) is an increasingly valuable tool in managing these patients, with various devices and configurations available. Critically ill patients receiving tMCS are at risk for complications and deconditioning associated with prolonged bed rest, making it essential to implement strategies that promote mobility when feasible. We advocate for a tailored approach to the selection and management of tMCS in patients with cardiogenic shock. This approach focuses on the early identification of patients who may benefit from tMCS before further deterioration, alongside the selection of devices that provide ventricular-specific support and facilitate upper-body cannulation to enhance mobilization while also considering patients' potential exit strategies from tMCS. Understanding this approach is vital to appropriately facilitating safe and effective mobilization.

Acute kidney injury (AKI) is a frequent complication of sepsis. While impaired renal venous reflux indicates renal congestion, the relationship between AKI outcomes and hemodynamic parameters remains debated. This study aimed to investigate the utility of renal venous flow patterns in various regions of septic patients and to explore the association between hemodynamic parameters and renal function prognosis.

In this single-center, prospective longitudinal study, adult sepsis patients diagnosed with AKI were enrolled. Renal ultrasonography was performed within 24 h of ICU admission (D1), then repeated at D3 and D5. Patterns of proximal renal venous flow (PRVF) and intrarenal venous flow (IRVF) patterns were confirmed by two blinded sonographers. Kaplan-Meier survival analysis was used to evaluate renal prognosis, and cumulative incidence curves were generated for renal function recovery time.

The study included 96 septic patients. Inconsistencies between PRVF and IRVF patterns occurred in 31.9%, with PRVF patterns being more severe in 88% of these. A relatively strong correlation was observed between PRVF and CVP, but this trend was less evident in IRVF. For RVSI of PRVF at ICU admission, the AUC to predict 28-day renal function prognosis was 0.626 (95% CI 0.502-0.750, P = 0.044), while combined PRVF and IRVF had a higher predictive ability (AUC 0.687, 95% CI 0.574-0.801, P = 0.003). The 28-day renal prognosis was poorer in the PRVF 5-day non-improvement group compared to the 3-day improvement group (P = 0.001) and 5-day improvement group (P = 0.012). Patients with a persistent monophasic PRVF pattern within 5 days had a worse prognosis than the non-monophasic group (P = 0.005).

Our study reveals that patterns of PRVF and IRVF are not entirely congruent, stepwise evaluation is useful in determining the intervention site for renal vein reflux disorders. Combined PRVF and IRVF had a higher predictive ability for 28-day renal function prognosis. Early improvement in renal venous congestion is crucial for better renal function prognosis. This study is registered with ClinicalTrials.gov, number NTC06159010. Retrospectively registered 28 November 2023.

Kidney failure with replacement therapy and cardiovascular disease are frequently comorbid. In patients with kidney failure with replacement therapy, cardiovascular disease is a major contributor to morbidity and mortality. Conventional thrice-weekly in-center dialysis confers risk factors for cardiovascular disease, including acute hemodynamic fluctuations and rapid shifts in volume and solute concentration. Home hemodialysis and peritoneal dialysis (PD) may offer benefits in attenuation of cardiovascular disease risk factors primarily through improved volume and BP control, reduction (or slowing progression) of left ventricular mass, decreased myocardial stunning, and improved bone and mineral metabolism. Importantly, although trial data are available for several of these risk factors for home hemodialysis, evidence for PD is limited. Among patients with prevalent cardiovascular disease, home hemodialysis and PD may also have potential benefits. PD may offer particular advantages in heart failure given it removes volume directly from the splanchnic circulation, thus offering an efficient method of relieving intravascular congestion. PD also avoids the risk of blood stream infections in patients with cardiac devices or venous wires. We recognize that both home hemodialysis and PD are also associated with potential risks, and these are described in more detail. We conclude with a discussion of barriers to home dialysis and the critical importance of interdisciplinary care models as one component of advancing health equity with respect to home dialysis.

Greater splanchnic nerve ablation may improve hemodynamics in patients with heart failure and preserved ejection fraction (HFpEF).

To explore the feasibility and safety of endovascular right-sided splanchnic nerve ablation for volume management (SAVM).

This was a phase 2, double-blind, 1:1, sham-controlled, multicenter, randomized clinical trial conducted at 14 centers in the US and 1 center in the Republic of Georgia. Patients with HFpEF, left ventricular ejection fraction of 40% or greater, and invasively measured peak exercise pulmonary capillary wedge pressure (PCWP) of 25 mm Hg or greater were included. Study data were analyzed from May 2023 to June 2024.

SAVM vs sham control procedure.

The primary efficacy end point was a reduction in legs-up and exercise PCWP at 1 month. The primary safety end point was serious device- or procedure-related adverse events at 1 month. Secondary efficacy end points included HF hospitalizations, changes in exercise function and health status through 12 months, and baseline to 1-month change in resting, legs-up, and 20-W exercise PCWP.

A total of 90 patients (median [range] age, 71 [47-90] years; 58 female [64.4%]) were randomized at 15 centers (44 SAVM vs 46 sham). There were no differences in adverse events between groups. The primary efficacy end point did not differ between SAVM or sham (mean between-group difference in PCWP, -0.03 mm Hg; 95% CI, -2.5 to 2.5 mm Hg; P = .95). There were also no differences in the secondary efficacy end points. There was no difference in the primary safety end point between the treatment (6.8% [3 of 44]) and sham (2.2% [1 of 46]) groups (difference, 4.6%; 95% CI, -6.1% to 15.4%; P = .36). There was no difference in the incidence of orthostatic hypotension between the treatment (11.4% [5 of 44]) and sham (6.5% [3 of 46]) groups (difference, 4.9%; 95% CI, -9.2% to 18.8%; P = .48).

Results show that SAVM was safe and technically feasible, but it did not reduce exercise PCWP at 1 month or improve clinical outcomes at 12 months in a broad population of patients with HFpEF.

ClinicalTrials.gov Identifier: NCT04592445.

Clinical congestion remains a major cause of hospitalization and re-hospitalizations in patients with chronic heart failure (HF). Despite the high prevalence of this issue and clinical concern in HF practice, there is limited understanding of the complex pathophysiology relating to the "congestion" of congestive HF. There is no unifying definition or clear consensus on what is meant or implied by the term "congestion." Further, the discordance in study findings relating congestion to physical signs and symptoms of HF, cardiac hemodynamics, or metrics of weight change or fluid loss with diuretic therapy has not added clarity. In this review, these factors will be discussed to add perspective to this issue and consider the factors driving "congestion." There remains a need to better understand the roles of fluid retention promoting intravascular and interstitial compartment expansions, blood volume redistribution from venous reservoirs, altered venous structure and capacity, elevated cardiac filling pressure hemodynamics, and heterogeneous intravascular volume profiles (plasma volume and red blood cell mass) with a goal to help demystify "congestion" in HF. Further, this includes highlighting the importance of recognizing that congestion is not the result of a single pathway but a complex of responses some of which produce symptoms while others do not; yet, we confine these varied responses to the single and somewhat vague term "congestion."

Previous research suggested that exposure to long-lasting or repeated laboratory stressors may lead to rearrangement of cardiovascular control, with a shift of regulation mechanisms from dominant cardiac to dominant vascular influences between the early and late response phases, respectively. This study investigated whether similar rearrangement occurs during life stress accompanying chronic disease by analyzing also associations between cortisol level and cardiovascular variables in patients with fibromyalgia (FM). In 47 women with FM and 36 healthy women (HW), cardiovascular recordings were taken during active body posture changes (sitting, lying down, and standing). Moreover, hair cortisol concentration (HCC) was obtained. During standing, which involved orthostatic challenge, FM patients showed higher total peripheral resistance (TPR) but lower stroke volume (SV), cardiac output (CO), and baroreflex sensitivity than HW. During sitting and lying down, TPR was more closely associated with blood pressure (BP) than CO in FM patients; in contrast, CO was more closely associated with BP than TPR in HW. HCC correlated positively with TPR and BP in FM patients, but negatively with TPR and BP and positively with SV and CO in HW. Results suggest that chronic disease-related stress is associated with alterations in cardiovascular regulation toward greater involvement of vascular than cardiac mechanisms in BP control. Stress-related cortisol release may contribute to the long-term rearrangement of autonomic regulation. At the behavioral level, the dominance of vascular over cardiovascular control may relate to reduced somatic mobilization during an active fight-flight response in favor of passive and behaviorally immobile coping.

For decades standard teaching recommended salt intake (sodium) reduction in patients suffering from heart failure. Neurohumoral activation with subsequent fluid retention provided a solid rationale for this long-standing recommendation. Until recently no large randomized clinical trial of sodium restriction was available, while some observational studies and metanalyses even suggested a worse outcome with strict sodium restriction in patients with heart failure.

In this narrative review we aimed to extricate from the literature whether strict sodium restriction is beneficial in patients with heart failure. We searched PubMed indexed articles between 2000 and 2023 for these terms: heart failure, salt, sodium, fluid intake.

Most randomized trials were small and showed a wide heterogeneity of interventions. A single large, randomized clinical trial was stopped early due to futility. Overall, there is no evidence that severe sodium restriction reduces the incidence of mortality and hospitalization in patients with heart failure. Quality of life and functional class may improve slightly with sodium restriction.

Morbidity and mortality are not reduced with sodium restriction in patients with heart failure, although some symptomatic improvement may be expected.

Congestion is a common cause of clinical deterioration and the most common clinical presentation at admission in acute heart failure (HF). Therefore, finding effective and sustainable ways to alleviate congestion has become a crucial goal for treating HF patients. Congestion is a result of complex underlying pathophysiology; therefore, it is not a direct cause of the disease but its consequence. Any therapy that directly promotes sodium/water removal only, thus targeting only clinical symptoms, neither modifies the natural course of the disease nor improves prognosis. This review aims to provide a comprehensive evaluation of the current decongestive therapies and propose a new (not diuretic-centred) paradigm of long-term congestion management in HF that attempts to correct the underlying pathophysiology, thus improving congestion, preventing its development, and favourably altering the natural course of the disease rather than merely treating its symptoms.

Incomplete decongestion is the main cause of readmission in the early post-discharge period of a hospitalization for acute heart failure. Recent heart failure guidelines have highlighted initiation and rapid up-titration of quadruple therapy with angiotensin receptor neprilysin inhibitor, beta adrenergic receptor blocker, mineralocorticoid receptor antagonist, and sodium glucose cotransporter 2 inhibitor to prevent hospitalizations for heart failure with reduced ejection fraction. However, full decongestion remains the foremost therapeutic goal of hospitalization for heart failure. While early addition of sodium glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists may be helpful, the value of the other therapeutics comes after decongestion is complete.

Comprehensive uptitration of neurohormonal blockade targets fundamental mechanisms underlying development of congestion and may be an additional approach for decongestion after acute heart failure (AHF).

This hypothesis was tested in the STRONG-HF (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by N-Terminal Pro-Brain Natriuretic Peptide Testing of Heart Failure Therapies) trial.

In STRONG-HF, patients with AHF were randomized to the high-intensity care (HIC) arm with fast up-titration of neurohormonal blockade or to usual care (UC). Successful decongestion was defined as an absence of peripheral edema, pulmonary rales, and jugular venous pressure <6 cm.

At baseline, the same proportion of patients in both arms had successful decongestion (HIC 48% vs UC 46%; P = 0.52). At day 90, higher proportion of patients in the HIC arm (75%) experienced successful decongestion vs the UC arm (68%) (P = 0.0001). Each separate component of the congestion score was significantly better in the HIC arm (all, P < 0.05). Additional markers of decongestion also favored the HIC: weight reduction (adjusted mean difference: -1.36 kg; 95% CI: -1.92 to -0.79 kg), N-terminal pro-B-type natriuretic peptide level, and lower orthopnea severity (all, P < 0.001). More effective decongestion was achieved despite a lower mean daily dose of loop diuretics at day 90 in the HIC arm. Among patients with successful decongestion at baseline, those in the HIC arm had a significantly better chance of sustaining decongestion at day 90. Successful decongestion in all subjects was associated with a lower risk of 180-day HF readmission or all-cause death (HR: 0.40; 95% CI: 0.27-0.59; P < 0.0001).

In STRONG-HF, intensive uptitration of neurohormonal blockade was associated with more efficient and sustained decongestion at day 90 and a lower risk of the primary endpoint.

Splanchnic vasoconstriction augments transfer of blood volume from the abdomen into the thorax, which may increase filling pressures and hemodynamic congestion in patients with noncompliant hearts. Therapeutic interruption of splanchnic nerve activity holds promise to reduce hemodynamic congestion in patients with heart failure with preserved ejection fraction (HFpEF). Here we describe (1) the rationale and design of the first sham-controlled, randomized clinical trial of splanchnic nerve ablation for HFpEF and (2) the 12-month results of the lead-in (open-label) trial's participants.

REBALANCE-HF is a prospective, multicenter, randomized, double-blinded, sham-controlled clinical trial of endovascular, transcatheter, right-sided greater splanchnic nerve ablation for volume management (SAVM) in patients with HFpEF. The primary objectives are to evaluate the safety and efficacy of SAVM and identify responder characteristics to inform future studies. The trial consists of an open-label lead-in phase followed by the randomized, sham-controlled phase. The primary efficacy endpoint is the reduction in pulmonary capillary wedge pressure (PCWP) at 1-month follow-up compared to baseline during passive leg raise and 20W exercise. Secondary and exploratory endpoints include health status (Kansas City Cardiomyopathy Questionnaire), 6-minute walk test distance, New York Heart Association class, and NTproBNP levels at 3, 6 and 12 months. The primary safety endpoint is device- or procedure-related serious adverse events at the 1-month follow-up.

The lead-in phase of the study, which enrolled 26 patients with HFpEF who underwent SAVM, demonstrated favorable safety outcomes and reduction in exercise PCWP at 1 month post-procedure and improvements in all secondary endpoints at 6 and 12 months of follow-up. The randomized phase of the trial (n = 44 SAVM; n = 46 sham) has completed enrollment, and follow-up is ongoing.

REBALANCE-HF is the first sham-controlled randomized clinical trial of greater splanchnic nerve ablation in HFpEF. Initial 12-month open-label results are promising, and the results of the randomized portion of the trial will inform the design of a future pivotal clinical trial. SAVM may offer a promising therapeutic option for patients with HFpEF.

NCT04592445.

The effects of initiating sacubitril/valsartan in patients with stable heart failure with reduced ejection fraction (HFrEF) on response to fluid and sodium expansion are unknown.

We have explored changes in natriuresis, diuresis, and congestion in response to the administration of intravenous fluid/sodium load in patients with HFrEF before as compared to after the initiation of sacubitril/valsartan. At baseline (before sacubitril/valsartan initiation) and 2 and 3 months after the initiation, patients underwent an evaluation that consisted of three phases of 3 h: the rest phase (0-3 h), the load phase (3-6 h) in which 1 L of intravenous Ringer solution was administered, and the diuretic phase (6-9 h) at the beginning of which furosemide was administered. Overall, 216 patients completed the study. In comparison to baseline values, at 2 and 3 months after sacubitril/valsartan initiation, patients' diuresis and natriuresis in response to Ringer administration significantly increased (mean difference: 38.8 [17.38] ml, p = 0.0040, and 9.6 [2.02] mmol, p < 0.0001, respectively). Symptoms and signs of congestion after the fluid/sodium challenge were significantly decreased at months 2 and 3 compared to baseline. Compared to baseline, there was also an increment of natriuresis after furosemide administration on sacubitril/valsartan (9.8 [5.13] mmol, p = 0.0167). There was a significant decrease in body weight in subsequent visits when compared to baseline values (-0.50 [-12.7, 7.4] kg at 2 months, and -0.75 [-15.9, 7.5] kg at 3 months; both p < 0.0001).

The initiation of sacubitril/valsartan in HFrEF patients was associated with improvements in natriuresis, diuresis, and weight loss and better clinical adaptation to potentially decongestive stressors.

Residual venous congestion is a major contributor to readmission of patients with heart failure, and the venous excess ultrasound (VExUS) score is a potentially useful tool to evaluate systemic congestion.

To investigate the association between VExUS score before hospital discharge among patients with heart failure and the risk of readmission due to acute decompensated heart failure (ADHF) within 90 days after discharge.

This prospective cohort study enrolled adults with signs and symptoms of ADHF, left ventricular ejection fraction of 40% or below (heart failure with reduced ejection fraction), New York Heart Association functional class II to IV symptoms, and clinical evidence of venous congestion necessitating intravenous diuretics. Just prior to discharge, we conducted VExUS score evaluation. The primary outcome was a composite endpoint of readmission or emergency visits due to ADHF within 90 days following hospital discharge. Statistical significance was set at p < 0.05.

The cohort comprised 49 individuals, 11 (22.4%) of whom experienced the primary outcome. At discharge, 34.7% of participants had VExUS score 2 or 3. Patients with VExUS 2 and 3 had a higher proportion of the primary outcome when compared with patients with VExUS of 0 (35.3% versus 9%, p = 0.044).

A significant proportion of patients with heart failure with reduced ejection fraction admitted for ADHF presented clinical and ultrasound signs of residual congestion at discharge. Patients with VExUS score of 2 or 3 at the time of hospital discharge were found to be at higher risk of readmissions or emergency visits due to ADHF after 90 days.

A hallmark of heart failure (HF), whether it presents itself during rest or periods of physical exertion, is the excessive elevation of intracardiac filling pressures at rest or with exercise. Many mechanisms contribute to the elevated intracardiac filling pressures, and notably, the concept of volume redistribution has gained attention as a cause of the elevated intracardiac filling pressures in patients with HF, particularly HF with preserved ejection fraction, who often present without symptoms at rest, with shortness of breath and fatigue appearing only during exertion. This phenomenon suggests cardiopulmonary system non-compliance and inappropriate volume distribution between the stressed and unstressed blood volume components. A substantial proportion of the intravascular blood volume is in the splanchnic vascular compartment in the abdomen. Preclinical and clinical investigations support the critical role of the sympathetic nervous system in modulating the capacitance and compliance of the splanchnic vascular bed via modulation of the greater splanchnic nerve (GSN). The GSN activation by stressors such as exercise causes excessive splanchnic vasoconstriction, which may contribute to the decompensation of chronic HF via volume redistribution from the splanchnic vascular bed to the central compartment. Accordingly, for example, GSN ablation for volume management has been proposed as a potential therapeutic intervention to increase unstressed blood volume. Here we provide a comprehensive review of the role of splanchnic circulation in the pathogenesis of HF and potential novel treatment options for redistributing blood volume to improve symptoms and prognosis in patients with HF.

Congestion not only represents a cardinal sign of heart failure (HF) but is also now recognized as the primary cause of hospital admissions, rehospitalization, and mortality among patients with acute heart failure (AHF). Congestion can manifest through various HF phenotypes in acute settings: volume overload, volume redistribution, or both. Recognizing the congestion phenotype is paramount, as it implies different therapeutic strategies for decongestion. Among patients with AHF, achieving complete decongestion is challenging, as more than half still experience residual congestion at discharge. Residual congestion is one of the strongest predictors of future cardiovascular events and poor outcomes. Through this review, we try to provide a better understanding of the congestion phenomenon among patients with AHF by highlighting insights into the pathophysiological mechanisms behind congestion and new diagnostic and management tools to achieve and maintain efficient decongestion.

The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression.

Male ZSF1 obese rats were subjected to radiofrequency renal denervation (RF-RDN) or sham procedure at either 8 weeks or 20 weeks of age and assessed for cardiovascular function, exercise capacity, and cardiorenal fibrosis. Renal norepinephrine and renal nerve tyrosine hydroxylase staining were performed to quantify denervation following RF-RDN. In addition, renal injury, oxidative stress, inflammation, and profibrotic biomarkers were evaluated to determine pathways associated with RDN. RF-RDN significantly reduced renal norepinephrine and tyrosine hydroxylase content in both study cohorts. RF-RDN therapy performed at 8 weeks of age attenuated cardiac dysfunction, reduced cardiorenal fibrosis, and improved endothelial-dependent vascular reactivity. These improvements were associated with reductions in renal injury markers, expression of renal NLR family pyrin domain containing 3/interleukin 1β, and expression of profibrotic mediators. RF-RDN failed to exert beneficial effects when administered in the 20-week-old HFpEF cohort.

Our data demonstrate that early RF-RDN therapy protects against HFpEF disease progression in part due to the attenuation of renal fibrosis and inflammation. In contrast, the renoprotective and left ventricular functional improvements were lost when RF-RDN was performed in later HFpEF progression. These results suggest that RDN may be a viable treatment option for HFpEF during the early stages of this systemic inflammatory disease.

Contrasting findings on the mechanisms of chronic pain and hypertension development render the current conventional evidence of a negative relationship between blood pressure (BP) and pain severity insufficient for developing personalized treatments. In this interdisciplinary study, patients with fibromyalgia (FM) exhibiting clinically normal or elevated BP, alongside healthy participants were assessed. Different pain sensitization responses were evaluated using a dynamic 'slowly repeated evoked pain' (SREP) measure, as well as static pain pressure threshold and tolerance measures. Cardiovascular responses to clino-orthostatic (lying-standing) challenges were also examined as acute re- and de-hydration events, challenging cardiovascular and cerebrovascular homeostasis. These challenges involve compensating effects from various cardiac preload or afterload mechanisms associated with different homeostatic body hydration statuses. Additionally, hair cortisol concentration was considered as a factor with an impact on chronic hydration statuses. Pain windup (SREP) and lower pain threshold in FM patients were found to be related to BP rise during clinostatic (lying) rehydration or orthostatic (standing) dehydration events, respectively. These events were determined by acute systemic vasoconstriction (i.e., cardiac afterload response) overcompensating for clinostatic or orthostatic cardiac preload under-responses (low cardiac output or stroke volume). Lower pain tolerance was associated with tonic blood pressure reduction, determined by permanent hypovolemia (low stroke volume) decompensated by permanent systemic vasodilation. In conclusion, the body hydration status profiles assessed by (re)activity of systemic vascular resistance and effective blood volume-related measures can help predict the risk and intensity of different pain sensitization components in chronic pain syndrome, facilitating a more personalized management approach.

Heart failure (HF) with preserved ejection fraction (HFpEF) is an increasingly frequent form and is estimated to be the dominant form of HF. On the other hand, HFpEF is a syndrome with systemic involvement, and it is characterized by multiple cardiac and extracardiac pathophysiological alterations. The increasing prevalence is currently reaching epidemic levels, thereby making HFpEF one of the greatest challenges facing cardiovascular medicine today. Compared to HF with reduced ejection fraction (HFrEF), the medical attitude in the case of HFpEF was a relaxed one towards the disease, despite the fact that it is much more complex, with many problems related to the identification of physiopathogenetic mechanisms and optimal methods of treatment. The current medical challenge is to develop effective therapeutic strategies, because patients suffering from HFpEF have symptoms and quality of life comparable to those with reduced ejection fraction, but the specific medication for HFrEF is ineffective in this situation; for this, we must first understand the pathological mechanisms in detail and correlate them with the clinical presentation. Another important aspect of HFpEF is the diversity of patients that can be identified under the umbrella of this syndrome. Thus, before being able to test and develop effective therapies, we must succeed in grouping patients into several categories, called phenotypes, depending on the pathological pathways and clinical features. This narrative review critiques issues related to the definition, etiology, clinical features, and pathophysiology of HFpEF. We tried to describe in as much detail as possible the clinical and biological phenotypes recognized in the literature in order to better understand the current therapeutic approach and the reason for the limited effectiveness. We have also highlighted possible pathological pathways that can be targeted by the latest research in this field.

Most episodes of acute heart failure (AHF) are characterized by increasing signs and symptoms of congestion, manifested by edema, pleura effusion and/or ascites. Immediately and repeatedly administered intravenous (IV) loop diuretics currently represent the mainstay of initial therapy aiming to achieve adequate diuresis/natriuresis and euvolemia. Despite these efforts, a significant proportion of patients have residual congestion at discharge, which is associated with a poor prognosis. Therefore, a standardized approach is needed. The door to diuretic time should not exceed 60 min. As a general rule, the starting IV dose is 20-40 mg furosemide equivalents in loop diuretic naïve patients or double the preexisting oral home dose to be administered via IV. Monitoring responses within the following first hours are key issues. (1) After 2 h, spot urinary sodium should be ≥50-70 mmol/L. (2) After 6 h, the urine output should be ≥100-150 mL/hour. If these target measures are not reached, the guidelines currently recommend a doubling of the original dose to a maximum of 400-600 mg furosemide per day and in patients with severely impaired kidney function up to 1000 mg per day. Continuous infusion of loop diuretics offers no benefit over intermittent boluses (DOSE trial). Emerging evidence by recent randomized trials (ADVOR, CLOROTIC) supports the concept of an early combination diuretic therapy, by adding either acetazolamide (500 mg IV once daily) or hydrochlorothiazide. Acetazolamide is particularly useful in the presence of a baseline bicarbonate level of ≥27 mmol/L and remains effective in the presence of preexisting/worsening renal dysfunction but should be used only in the first three days to prevent severe metabolic disturbances. Patients should not leave the hospital when they are still congested and/or before optimized long-term guideline-directed medical therapy has been initiated. Special attention should be paid to AHF patients during the vulnerable post-discharge period, with an early follow-up visit focusing on up-titrate treatments of recommended doses within 2 weeks (STRONG-HF).

The field of heart failure has evolved in terms of the therapies that are available including pharmaceutical and device therapies. There is now substantial randomized trial data to indicate that dietary sodium restriction does not provide the reduction in clinical events with accepted heterogeneity in the clinical trial results. Dietary sodium restriction should be considered for some but not all patients and with different objectives than clinical outcomes but instead for potential quality of life benefit. In addition, fluid restriction, once the mainstay of clinical practice, has not shown to be of any additional benefit for patients in hospital or in the ambulatory care setting and therefore should be considered to be used cautiously (if at all) in clinical practice. Further developments and clinical trials are needed in this area to better identify patients who may benefit or have harm from these lower cost interventions and future research should focus on large scale, high quality, clinical trials rather than observational data to drive clinical practice.

While ivabradine has demonstrated benefits in heart rate control and prognosis for chronic heart failure patients, its application in acute decompensated heart failure remains underexplored.

For patients with acute decompensated heart failure with reduced ejection fraction (HFrEF) who are intolerant to β-blockers or unable to further titrate their dosage, the use of ivabradine is hypothesized to be effective and safe is improving outcomes.

This retrospective, multicenter database analysis included patients with hospitalized decompensated heart failure with a left ventricular ejection fraction of ≤40% from June 1, 2015 to December 31, 2020. The exclusion criteria were a baseline heart rate of <70 bpm, previous use of ivabradine, mortality during admission, existing atrial fibrillation, or atrial flutter. The primary outcome was the composite of cardiovascular death and hospitalization for heart failure.

Of the 4163 HFrEF patients analyzed, 684 (16.4%) were administered ivabradine during their index admission. After matching, there were 617 patients in either group. The results indicated that ivabradine use was not significantly associated with the risk of the primary composite outcome (hazard ratio: 1.10; 95% confidence interval: 0.94-1.29). Similarly, the risk of secondary outcomes and adverse renal events did not significantly differ between the ivabradine and non-ivabradine cohorts (all p > .05).

For hospitalized acute decompensated heart failure patients who are intolerant to β-blockers or cannot further titrate them, ivabradine offers a consistent therapeutic effect. No significant disparities were noted between the ivabradine and non-ivabradine groups in heart failure hospitalization and cardiovascular death.

This review paper presents a review of the evolution of this disease throughout the centuries, describes and summarizes the pathophysiologic mechanisms, briefly discusses the mechanism of action of diuretics, presents their role in decongesting heart failure in patients, and reveals the data behind ultrafiltration in the management of acutely or chronically decompensated heart failure (ADHF), focusing on all the available data and advancements in this field. Acutely decompensated heart failure (ADHF) presents a critical clinical condition characterized by worsening symptoms and signs of heart failure, necessitating prompt intervention to alleviate congestion and improve cardiac function. Diuretics have traditionally been the mainstay for managing fluid overload in ADHF. Mounting evidence suggests that due to numerous causes, such as coexisting renal failure or chronic use of loop diuretics, an increasing rate of diuretic resistance is noticed and needs to be addressed. There has been a series of trials that combined diuretics of different categories without the expected results. Emerging evidence suggests that ultrafiltration may offer an alternative or adjunctive approach.

Acute decompensated heart failure (ADHF) is a major cause of hospitalizations in older adults, leading to high mortality, morbidity, and healthcare costs. To address the persistent poor outcomes in ADHF, novel device-based approaches targeting specific pathophysiological mechanisms are urgently needed. The recently introduced DRI2P2S classification categorizes these innovative therapies based on their mechanisms. Devices include dilators (increasing venous capacitance), removers (directly removing sodium and water), inotropes (enhancing left ventricular contractility), interstitials (accelerating lymph removal), pushers (increasing renal arterial pressure), pullers (decreasing renal venous pressure), and selective drippers (selective intrarenal drug infusion). Some are tailored for chronic HF, while others focus on the acute setting. Most devices are in early development, necessitating further research to understand mechanisms, assess clinical effectiveness, and ensure safety before routine use in ADHF management. Exploring these innovative device-based strategies may lead to improved outcomes and revolutionize HF treatment in the future.

The paired kidneys play a significant role in the human body due to the multitude of physiological tasks. Complex biochemical processes keep the sensitive electrolyte and water balance stable and thus ensure the organism's ability to adapt to exogenous and endogenous factors, which is essential for survival. The drug class of diuretics includes substances with very differing pharmacological characteristics. The functioning of the nephron is therefore indispensable for a deeper understanding of the pharmacodynamics, pharmacokinetics and side effect profile of diuretics. In the treatment of acute heart failure with pulmonary congestion, certain diuretics represent an important therapeutic option to counteract hypervolemia and thus an increase in preload. According to current data, diuretics have no proven benefits in the treatment or prevention of acute kidney injury but they can counteract hypervolemia and under certain conditions even reduce the use of renal replacement procedures.

Heart failure (HF) is a leading cause of morbidity and mortality and a major public health problem. Both overhydration and dehydration are non-physiological states of the body that can adversely affect human health. Congestion and residual congestion are common in patients hospitalized for HF and are associated with poor prognosis and high rates of rehospitalization. However, the clinical problem of dehydration is also prevalent in healthcare and community settings and is associated with increased morbidity and mortality. This article provides a comprehensive review of the issue of congestion and dehydration in HF, including HF guidelines, possible causes of dehydration in HF, confirmed and potential new diagnostic methods. In particular, a full database search on the relationship between dehydration and HF was performed and all available evidence in the literature was reviewed. The novel hypothesis of chronic subclinical hypohydration as a modifiable risk factor for HF is also discussed. It is concluded that maintaining euvolemia is the cornerstone of HF management. Physicians have to find a balance between decongestion therapy and the risk of dehydration.

Background: We evaluated the bio-humoral and non-invasive haemodynamic correlates of renal congestion evaluated by Doppler renal venous flow (RVF) across the heart failure (HF) spectrum, from asymptomatic subjects with cardiovascular risk factors (Stage A) and structural heart disease (Stage B) to patients with clinically overt HF (Stage C). Methods: Ultrasound evaluation, including echocardiography, lung ultrasound and RVF, along with blood and urine sampling, was performed in 304 patients. Results: Continuous RVF was observed in 230 patients (76%), while discontinuous RVF (dRVF) was observed in 74 (24%): 39 patients had pulsatile RVF, 18 had biphasic RVF and 17 had monophasic RVF. Stage C HF was significantly more common among patients with dRVF. Monophasic RVF was associated with worse renal function and a higher urinary albumin-to-creatinine ratio (uACR). After adjusting for hypertension, diabetes mellitus, the presence of Stage C HF and serum creatinine levels, worsening RVF patterns were associated with higher NT-proBNP levels, worse right ventricular-arterial coupling, larger inferior vena cava and higher echo-derived pulmonary artery wedge pressure. This trend was confirmed when only patients with HF Stage C were analysed after adjusting for the left ventricle ejection fraction (LVEF). Conclusion: Abnormal RVF is common across the HF spectrum. Worsening RVF patterns are independently associated with increased congestion, worse non-invasive haemodynamics and impaired RV-arterial coupling. RVF evaluation could refine prognostic stratification across the HF spectrum, irrespective of LVEF.

Soon after haemodialysis was introduced into clinical practice, a high risk of cardiac death was noted in end-stage renal disease. However, only in the last decade has it become clear that any renal injury, acute or chronic, is associated with high overall and cardiovascular lethality. The need for early recognition of kidney damage in cardiovascular pathology to assess risk and develop tactics for patient management contributed to the emergence of the concept of the "cardiorenal syndrome" (CRS). CRS is a pathophysiological disorder of the heart and kidneys in which acute or chronic dysfunction of one of these organs leads to acute or chronic dysfunction of the other. The beneficial effect of ultrafiltration as a component of renal replacement therapy (RRT) is due to the elimination of hyperhydration, which ultimately affects the improvement in cardiac contractile function. This review considers the theoretical background, current status of CRS, and future potential of RRT, focusing on the benefits of ultrafiltration as a therapeutic option.

We aim to assess the theoretical impact of the atrial flow regulator (AFR) on survival in heart failure.

The prospective, multicentre, open-label, non-randomised PRELIEVE study (NCT03030274) assessed the safety and efficacy of the Occlutech AFR device in patients with symptomatic heart failure with reduced ejection fraction (HFrEF) (left ventricular ejection fraction (LVEF) ≥ 15% and <40%) or heart failure with preserved ejection fraction (HFpEF) (LVEF ≥40% and <70%) and elevated PCWP (≥15 mmHg at rest or ≥25 mmHg during exercise). In this analysis, after the first 60 patients completed 12 months of follow-up, the theoretical impact of AFR implantation on survival was assessed by comparing the observed mortality rate with the median predicted probability for one-year mortality. Each subject's risk of mortality was predicted from individual baseline data using the Meta-Analysis Global Group in Chronic HF (MAGGIC) prognostic model. A total of 87 patients (46% female, median age 69 years [IQR 62-74]) had undergone successful device implantation for the treatment of HFrEF (53%) and HFpEF (47%). Sixty patients had a complete 12 month follow-up. The median follow-up was 351 days (interquartile range [IQR] 202-370). Six (7%) patients died during follow-up (8.6 deaths per 100 patient-years; 95% confidence interval [CI] 2.7 to 15.5), all of which had HFrEF. The median predicted mortality rate for the overall study population was 12.2 deaths per 100 patient-years (95% CI 10.2 to 14.7). While the observed mortality rate (0 deaths per 100 patient-years) was significantly lower than the median predicted mortality rate (9.3 deaths per 100 patient-years; 95% CI 8.4 to 11.1) in patients with HFpEF (-9.3 deaths per 100 patient-years; 95% CI -11.1 to -8.4), there was no difference in patients with HFrEF (-3.6 deaths per 100 patient-years; 95% CI -9.5 to 3.0). Four deaths were HF-related deaths (5.7 HF-related deaths per 100 patient-years; 95% CI 1.4 to 11.9; 10.8 HF-related deaths per 100 patient-years; 95% CI 2.5 to 23.1 in the HFrEF subgroup).

In patients with HFpEF, the mortality rate following AFR implantation was lower than the predicted mortality rate. Dedicated randomised, controlled trials are needed - and currently ongoing - to investigate whether the AFR improves mortality.