Nurse-led diuretic titration via a point-of-care urinary sodium sensor in patients with acute decompensated heart failure (EASY-HF): A single-centre, randomized, open-label study.

AIMS: Early evaluation of the natriuretic response is recommended to guide diuretic therapy in acute decompensated heart failure (ADHF). However, its implementation in daily practice is hampered by implementation barriers and increased time constraints. The Readily Available Urinary Sodium Analysis in Patients with Acute Decompensated Heart Failure (EASY-HF) study assessed the feasibility, efficacy and safety of a nurse-led urinary sodium-based diuretic titration protocol with the use of a point-of-care urinary sodium sensor. METHODS AND RESULTS: The EASY-HF study was a single-centre, randomized, open-label study comparing diuretic management at the treating physician's discretion as standard of care (SOC) with a nurse-led natriuresis-guided protocol in patients with ADHF. The LAQUAtwin Sodium Meter (HORIBA) was used as point-of-care sensor to measure urine sodium concentration. The primary endpoint was natriuresis after 48 h. Secondary endpoints included safety profile and user-friendliness of both the protocol and the point-of-care sensor. Sixty patients were randomized towards SOC (n = 30) versus protocolized care (n = 30). The mean age was 80 ± 8 years, 25% were women and median N-terminal pro-B-type natriuretic peptide was 4667 (2667-7709) ng/L. Natriuresis after 48 h was significantly higher in the protocolized versus SOC group (820 ± 279 vs. 657 ± 273 mmol; p = 0.027). Pre-defined safety endpoints were similar among both groups. The sensor-based protocol was evaluated as easy to use by the nursing staff, and preferred over urinary collections. CONCLUSION: A nurse-led diuretic titration protocol via a point-of-care urinary sodium sensor was feasible, safe and resulted in an increased natriuresis in ADHF compared to SOC.

Clinical Significance of Exercise Pulmonary Hypertension With a Negative Diastolic Stress Test for Suspected Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Half of patients with heart failure with preserved ejection fraction (HFpEF) remain undiagnosed by resting evaluation alone. Therefore, exercise testing is proposed. The diastolic stress test (DST), however, has limited sensitivity. We aimed to determine the clinical significance of adding the mean pulmonary artery pressure over cardiac output (mPAP/CO) slope to the DST in suspected HFpEF. METHODS AND RESULTS: In this prospective cohort study, consecutive patients (n=1936) with suspected HFpEF underwent exercise echocardiography with simultaneous respiratory gas analysis. These patients were stratified by exercise E over e' (exE/e') and mPAP/CO slope, and peak oxygen uptake, natriuretic peptides (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and score-based HFpEF likelihood were compared. Twenty-two percent of patients (n=428) had exE/e'<15 despite a mPAP/CO slope>3 mm Hg/L per min, 24% (n=464) had a positive DST (exE/e'≥15), and 54% (n=1044) had a normal DST and slope. Percentage of predicted oxygen uptake was similar in the group with exE/e'<15 but high mPAP/CO slope and the positive DST group (-2% [-5% to +1%]), yet worse than in those with normal DST and slope (-12% [-14% to -9%]). Patients with exE/e'<15 but a high slope had NT-proBNP levels and H2FPEF (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder; filling pressure) scores intermediate to the positive DST group and the group with both a normal DST and slope. CONCLUSIONS: Twenty-two percent of patients with suspected HFpEF presented with a mPAP/CO slope>3 mm Hg/L per min despite a negative DST. These patients had HFpEF characteristics and a peak oxygen uptake as low as patients with a positive DST. Therefore, an elevated mPAP/CO slope might indicate HFpEF irrespective of the DST result.

An evidence-based screening tool for heart failure with preserved ejection fraction: the HFpEF-ABA score.

Heart failure with preserved ejection fraction (HFpEF) is under-recognized in clinical practice. Although a previously developed risk score, termed H2FPEF, can be used to estimate HFpEF probability, this score requires imaging data, which is often unavailable. Here we sought to develop an HFpEF screening model that is based exclusively on clinical variables and that can guide the need for echocardiography and further testing. In a derivation cohort (n = 414, 249 women), a clinical model using age, body mass index and history of atrial fibrillation (termed the HFpEF-ABA score) showed good discrimination (area under the curve (AUC) = 0.839 (95% confidence interval (CI) = 0.800-0.877), P < 0.0001). The performance of the model was validated in an international, multicenter cohort (n = 736, 443 women; AUC = 0.813 (95% CI = 0.779-0.847), P < 0.0001) and further validated in two additional cohorts: a cohort including patients with unexplained dyspnea (n = 228, 136 women; AUC = 0.840 (95% CI = 0.782-0.900), P < 0.0001) and a cohort for which HF hospitalization was used instead of hemodynamics to establish an HFpEF diagnosis (n = 456, 272 women; AUC = 0.929 (95% CI = 0.909-0.948), P < 0.0001). Model-based probabilities were also associated with increased risk of HF hospitalization or death among patients from the Mayo Clinic (n = 790) and a US national cohort across the Veteran Affairs health system (n = 3076, 110 women). Using the HFpEF-ABA score, rapid and efficient screening for risk of undiagnosed HFpEF can be performed in patients with dyspnea using only age, body mass index and history of atrial fibrillation.

Post-diuretic spot urine sodium assessment in acute heart failure: a retrospective analysis.

AIMS: To provide real-world data on post-diuretic spot urine sodium concentration (UNa) assessment in acute heart failure (AHF) and its implications for treatment. METHODS AND RESULTS: Automated query of the electronic medical record identified patients admitted to the cardiac intensive care unit of a single tertiary care hospital between November 2018 and December 2021, who received intravenous loop diuretics. Detailed manual chart review confirmed the AHF diagnosis. Stratification was performed based on whether post-diuretic UNa was assessed within 24 h of admission. AHF was confirmed in 340/380 identified patients. Post-diuretic UNa was assessed in 117 (34%), more frequently when ejection fraction was reduced and heart failure more advanced. Patients with versus without post-diuretic UNa assessment received higher doses of intravenous loop diuretics and more frequently acetazolamide and thiazide-like diuretics (p < 0.001 for all), resulting in similar urine output despite more advanced heart failure [2,488 mL (1,740-4,033 mL) vs. 2,400 mL (1,553-3,250 mL), respectively; p = 0.170]. Diuretic therapy remained more intense at discharge in the post-diuretic UNa group, with also a higher prescription rate of angiotensin-neprilysin inhibitors (p = 0.021). Serum creatinine increases/decreases were similarly frequent irrespectively from UNa assessment, with more dynamic changes observed in patients with UNa ≤ 80 mmol/L versus ≥ 81 mmol/L. After adjustments for baseline characteristics, the risk for death or heart failure readmission was similar in patients with versus without UNa assessment [HR (95%CI) = 1.43 (0.88-2.32); p = 0.150]. CONCLUSION: Post-diuretic UNa assessment in AHF was associated with more intense diuretic regimens, preserving urine output despite its use in a sicker population.

Renal Sodium Avidity in Heart Failure.

BACKGROUND: Increased renal sodium avidity is a hallmark feature of the heart failure syndrome. SUMMARY: Increased renal sodium avidity refers to the inability of the kidneys to elicit potent natriuresis in response to sodium loading. This eventually causes congestion, which is a major contributor to hospital admissions and mortality in heart failure. KEY MESSAGES: Important novel concepts such as the renal tamponade hypothesis, accelerated nephron loss, and the role of hypochloremia, the sympathetic nervous system, inflammation, the lymphatic system, and interstitial sodium buffers are involved in the pathophysiology of renal sodium avidity. A good understanding of these concepts is crucially important with respect to treatment recommendations regarding dietary sodium restriction, fluid restriction, rapid up-titration of guideline-directed medical therapies, combination diuretic therapy, natriuresis-guided diuretic therapy, use of hypertonic saline, and ultrafiltration.

Dietary sodium and fluid intake in heart failure. A clinical consensus statement of the Heart Failure Association of the ESC.

Sodium and fluid restriction has traditionally been advocated in patients with heart failure (HF) due to their sodium and water avid state. However, most evidence regarding the altered sodium handling, fluid homeostasis and congestion-related signs and symptoms in patients with HF originates from untreated patient cohorts and physiological investigations. Recent data challenge the beneficial role of dietary sodium and fluid restriction in HF. Consequently, the European Society of Cardiology HF guidelines have gradually downgraded these recommendations over time, now advising for the limitation of salt intake to no more than 5 g/day in patients with HF, while contemplating fluid restriction of 1.5-2 L/day only in selected patients. Therefore, the objective of this clinical consensus statement is to provide advice on fluid and sodium intake in patients with acute and chronic HF, based on contemporary evidence and expert opinion.

Mitral regurgitation in heart failure with preserved ejection fraction: The interplay of valve, ventricle, and atrium.

Mitral regurgitation (MR) is highly prevalent among patients with heart failure and preserved ejection fraction (HFpEF). Despite this combination being closely associated with unfavourable outcomes, it remains relatively understudied. This is partly due to the inherent heterogeneity of patients with HFpEF. To address this gap, dissecting HFpEF into mechanism-based phenotypes may offer a promising avenue for advancing our comprehension of these complex intertwined conditions. This review employs the validated CircAdapt model to explore the haemodynamic implications of moderate to severe MR across a well-defined spectrum of myocardial disease, characterized by impaired relaxation and reduced myocardial compliance. Both heart failure and mitral valve disease share overlapping symptomatology, primarily attributed to elevated pulmonary pressures. The intricate mechanisms contributing to these elevated pressures are multifaceted, potentially influenced by diastolic dysfunction, left atrial myopathy, and MR. Accurate evaluation of the haemodynamic and clinical impact of MR necessitates a comprehensive approach, taking into account the characteristics of both the left atrium and left ventricle, as well as their intricate interactions, which may currently be underemphasized in diagnostic practice. This holistic assessment is imperative for enhancing our understanding and refining therapeutic strategies within this patient cohort.

Non-invasive imaging in acute decompensated heart failure with preserved ejection fraction.

Non-invasive imaging plays an increasingly important role in emergency medicine, given the trend towards smaller, portable ultrasound devices, the integration of ultrasound imaging across diverse medical disciplines, and the growing evidence supporting its clinical benefits for the patient. Heart failure with preserved ejection fraction (HFpEF) provides a compelling illustration of the impactful role that imaging plays in distinguishing diverse clinical presentations of heart failure with numerous associated comorbidities, including pulmonary, renal, or hepatic diseases. While a preserved left ventricular ejection fraction might misguide the clinician away from diagnosing cardiac disease, there are several clues provided by cardiac, vascular, and lung ultrasonography, as well as other imaging modalities, to rapidly identify (decompensated) HFpEF. Congestion remains the primary reason why patients with heart failure (irrespective of ejection fraction) seek emergency care. Furthermore, comprehensive phenotyping is becoming increasingly important, considering the development of targeted treatments for conditions exhibiting HFpEF physiology, such as cardiac amyloidosis. Timely recognition in such cases has lasting implications for long-term outcomes.

Decongestion (instead of ultrafiltration?).

PURPOSE OF REVIEW: To summarize the contemporary evidence on decongestion strategies in patients with acute heart failure (AHF). RECENT FINDINGS: While loop diuretic therapy has remained the backbone of decongestive treatment in AHF, multiple randomized clinical trials suggest that early combination with other diuretic classes or molecules with diuretic properties should be considered. Mineralocorticoid receptor antagonists and sodium-glucose co-transporter-2 inhibitors are disease-modifying drugs in heart failure that favourably influence prognosis early on, advocating their start as soon as possible in the absence of any compelling contraindications. Short-term upfront use of acetazolamide in adjunction to intravenous loop diuretic therapy relieves congestion faster, avoids diuretic resistance, and may shorten hospitalization length. Thiazide-like diuretics remain a good option to break diuretic resistance. Currently, ultrafiltration in AHF remains mainly reserved for patient with an inadequate response to pharmacological treatment. SUMMARY: In most patients with AHF, decongestion can be achieved effectively and safely through combination diuretic therapies. Appropriate diuretic therapy may shorten hospitalization length and improve quality of life, but has not yet proven to reduce death or heart failure readmissions. Ultrafiltration currently has a limited role in AHF, mainly as bail-out strategy, but evidence for a more upfront use remains inconclusive.

mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis.

BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown. METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141). RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort. CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.

Evaluation and Management of Hyponatremia in Heart Failure.

PURPOSE OF REVIEW: To provide a contemporary overview of the pathophysiology, evaluation, and treatment of hyponatremia in heart failure (HF). RECENT FINDINGS: Potassium and magnesium losses due to poor nutritional intake and treatment with diuretics cause an intracellular sodium shift in HF that may contribute to hyponatremia. Impaired renal blood flow leading to a lower glomerular filtration rate and increased proximal tubular reabsorption lead to an impaired tubular flux through diluting distal segments of the nephron, compromising electrolyte-free water excretion. Hyponatremia in HF is typically a condition of impaired water excretion by the kidneys on a background of potassium and magnesium depletion. While those cations can and should be easily repleted, further treatment should mainly focus on improving the underlying HF and hemodynamics, while addressing congestion. For decongestive treatment, proximally acting diuretics such as sodium-glucose co-transporter-2 inhibitors, acetazolamide, and loop diuretics are the preferred options.

Cardiac dysfunction rather than aortic valve stenosis severity drives exercise intolerance and adverse haemodynamics.

AIMS: To study the impact of heart failure with preserved ejection fraction (HFpEF) vs. aortic stenosis (AS) lesion severity on left ventricular (LV) hypertrophy, diastolic dysfunction, left atrial (LA) dysfunction, haemodynamics, and exercise capacity. METHODS AND RESULTS: Patients (n = 206) with at least moderate AS (aortic valve area ≤0.85 cm/m2) and discordant symptoms underwent cardiopulmonary exercise testing with simultaneous echocardiography. The population was stratified according to the probability of underlying HFpEF by the heavy, hypertension, atrial fibrillation, pulmonary hypertension, elder, filling pressure (H2FPEF) score [0-5 (AS/HFpEF-) vs. 6-9 points (AS/HFpEF+)] and AS severity (Moderate vs. Severe). Mean age was 73 ± 10 years with 40% women. Twenty-eight patients had Severe AS/HFpEF+ (14%), 111 Severe AS/HFpEF- (54%), 13 Moderate AS/HFpEF+ (6%), and 54 Moderate AS/HFpEF- (26%). AS/HFpEF+ vs. AS/HFpEF- patients, irrespective of AS severity, had a lower LV global longitudinal strain, impaired diastolic function, reduced LV compliance, and more pronounced LA dysfunction. The pulmonary arterial pressure-cardiac output slope was significantly higher in AS/HFpEF+ vs. AS/HFpEF- (5.4 ± 3.1 vs. 3.9 ± 2.2 mmHg/L/min, respectively; P = 0.003), mainly driven by impaired cardiac output and chronotropic reserve, with signs of right ventricular pulmonary arterial uncoupling. AS/HFpEF+ vs. AS/HFpEF- was associated with a lower peak aerobic capacity (11.5 ± 3.7 vs. 15.9 ± 5.9 mL/min/kg, respectively; P < 0.0001) but did not differ between Moderate and Severe AS (14.7 ± 5.5 vs. 15.2 ± 5.9 mL/min/kg, respectively; P = 0.6). CONCLUSION: A high H2FPEF score is associated with a reduced exercise capacity and adverse haemodynamics in patients with moderate to severe AS. Both exercise performance and haemodynamics correspond better with intrinsic cardiac dysfunction than AS severity.

Biatrial myopathy in heart failure with preserved ejection fraction.

AIM: Left atrial (LA) myopathy is increasingly recognized as an important phenotypic trait in heart failure (HF) with preserved ejection fraction (HFpEF). Right atrial (RA) remodelling and dysfunction also develop in HFpEF, but little data are available regarding the clinical characteristics and pathophysiology among patients with isolated LA, RA, or biatrial myopathy. METHODS AND RESULTS: Patients with HFpEF underwent invasive haemodynamic exercise testing, comprehensive imaging including speckle tracking strain echocardiography, and clinical follow-up at Mayo Clinic between 2006 and 2018. LA myopathy was defined as LA volume index >34 ml/m2 and/or LA reservoir strain ≤24% and RA myopathy by RA volume index >39 ml/m2 in men and >33 ml/m2 in women and/or RA reservoir strain ≤19.8%. Of 476 consecutively evaluated patients with HFpEF defined by invasive exercise testing with evaluable atrial structure/function, 125 (26%) had no atrial myopathy, 147 (31%) had isolated LA myopathy, 184 (39%) had biatrial myopathy, and 20 (4%) had isolated RA myopathy. Patients with HFpEF and biatrial myopathy had more atrial fibrillation, poorer left ventricular systolic and diastolic function, more severe pulmonary vascular disease, tricuspid regurgitation, ventricular interdependence and right ventricular dysfunction, and poorer cardiac output reserve with exercise. There were 94 patients with events over a median follow-up of 2.9 (interquartile range 1.4-4.6) years. Individuals with biatrial myopathy had an 84% higher risk of HF hospitalization or death as compared to those with isolated LA myopathy (hazard ratio 1.84; 95% confidence interval 1.16-2.92, p = 0.01). CONCLUSIONS: Biatrial myopathy identifies patients with more advanced HFpEF characterized by more severe pulmonary vascular disease, right HF, poorer cardiac reserve, and a greater risk for adverse outcomes. Further study is required to define optimal strategies to treat and prevent biatrial myopathy in HFpEF.

Smartphone-based atrial fibrillation screening in the general population: feasibility and impact on medical treatment.

Aims: The aim of this study is to determine the feasibility, detection rate, and therapeutic implications of large-scale smartphone-based screening for atrial fibrillation (AF). Methods and results: Subjects from the general population in Belgium were recruited through a media campaign to perform AF screening during 8 consecutive days with a smartphone application. The application analyses photoplethysmography traces with artificial intelligence and offline validation of suspected signals to detect AF. The impact of AF screening on medical therapy was measured through questionnaires. Atrial fibrillation was detected in the screened population (n = 60.629) in 791 subjects (1.3%). From this group, 55% responded to the questionnaire. Clinical AF [AF confirmed on a surface electrocardiogram (ECG)] was newly diagnosed in 60 individuals and triggered the initiation of anti-thrombotic therapy in 45%, adjustment of rate or rhythm controlling strategies in 62%, and risk factor management in 17%. In subjects diagnosed with known AF before screening, a positive screening result led to these therapy adjustments in 9%, 39%, and 11%, respectively. In all subjects with clinical AF and an indication for oral anti-coagulation (OAC), OAC uptake increased from 56% to 74% with AF screening. Subjects with clinical AF were older with more co-morbidities compared with subclinical AF (no surface ECG confirmation of AF) (P < 0.001). In subjects with subclinical AF (n = 202), therapy adjustments were performed in only 7%. Conclusion: Smartphone-based AF screening is feasible at large scale. Screening increased OAC uptake and impacted therapy of both new and previously diagnosed clinical AF but failed to impact risk factor management in subjects with subclinical AF.

Country and health expenditure are major predictors of withholding anticoagulation in atrial fibrillation patients at high risk of stroke.

BACKGROUND: Guidelines for patients with atrial fibrillation (AF) at high thromboembolic risk recommend oral anticoagulants (OACs) for preventing stroke and systemic embolism (SE). The reasons for guideline non-adherence are still unclear. AIM: The aim is to identify clinical, demographic and non-patient characteristics associated with withholding OAC in patients with AF at high stroke risk. METHODS: Patients in the Global Anticoagulant Registry in the FIELD-AF, newly diagnosed with AF between March 2010 and August 2016, and with CHA2DS2-VASc Score≥2 (excluding sex), were grouped by OAC treatment at enrolment. Factors associated with OAC non-use were analysed by multivariable logistic regression. RESULTS: Of 40 416 eligible patients, 12 126 (30.0%) did not receive OACs at baseline. Globally, OAC prescription increased over time, from 60.4% in 2010-2011 to 74.7% in 2015-2016. Country of enrolment was the major predictor for OAC withholding (χ2-df=2576). Clinical predictors of OAC non-use included type of AF (χ2-df=404), history of bleeding (χ2-df=263) and vascular disease (χ2-df=99). OACs were used most frequently around the age of 75 years and decreasingly with younger as well as older age beyond 75 years (χ2-df=148). Non-cardiologists (χ2-df=201) and emergency room physicians (χ2-df=14) were less likely to prescribe OACs. OAC prescription correlated positively with country health expenditure. CONCLUSIONS: Approximately one out of three AF patients did not receive OAC, while eligible according to the guidelines. Country of enrolment was the major determinant of anticoagulation strategy, while higher country health expenditure was associated with lower likelihood of withholding anticoagulation.