Diuretic Dose Research Articles

Randomized trial to assess worsening renal function by adding dapagliflozin for acute decompensated heart failure.

Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 inhibitor, has been shown to reduce cardiovascular mortality among patients with chronic heart failure. We aimed to evaluate the impact on a worsening renal function (WRF) by adding DAPA as compared to standard decongestive therapy with loop diuretics alone. We enrolled 114 consecutive acute decompensated heart failure (ADHF) patients with a left ventricular ejection fraction (LVEF) of less than 50%. The patients were prospectively randomized to be assigned either to DAPA group who received DAPA at a dose of 10mg once daily within 24h after admission or conventional therapy group (CON group) who received loop diuretics alone. All patients were adjusted by increasing or decreasing the loop diuretic by 10mg to maintain a 1-2mL/kg/h urine output. The primary endpoint was the incidence of WRF, which was defined as an increase in the serum creatinine of ≥0.3mg/dL from baseline. The median age of the patients was 77 [interquartile range (IQR): 64, 85] years, 35% were female and the median LVEF was 33 [IQR: 28, 38] %. There was no significant difference in the incidence of WRF between the two groups (16.1%, n=9 vs. 12.1%, n=7, P value=0.54). The total dose of loop diuretics through day 7 was lower in the DAPA group than CON group (184±79.5mg vs. 214±66.5mg, P value=0.03). This randomized prospective trial revealed the addition of DAPA within 24h after admission reduced the diuretic dose without WRF.

Clinical impact of right atrium function on tricuspid regurgitation

Abstract Background tricuspid regurgitation (TR) is frequent, and its related systemic venous congestion is associated with mortality. Purpose This study aims to evaluate the role of right atrial (RA) function, measured using the strain technique, on the medium- to long-term clinical effects of tricuspid regurgitation (TR). Our primary objective was to analyze the impact of RA function, measured at baseline, on a composite endpoint consisting of death and/or hospitalization for predominantly right-sided heart failure. The secondary endpoints are hospitalizations, worsening of renal function, and an increase in diuretic dosage (DD). Methods We performed a single center, prospective, observational study regarding adult patients with tricuspid regurgitation and measurable effective regurgitant orifice area (EROA) and a state of hemodynamic stability that underwent a complete echocardiography and full cardiologic evaluation in our Institution, from January 2020 to February 2023. Those patients with acute HF, poor quality imaging, previous repair or prosthetic replacement of the tricuspid valve, and severe renal or hepatic insufficiency were excluded. Patients were assessed clinically at each follow up. Results 134 patients were included (females 62%, mean age 73 ± 13 years old). Median follow up was 23,5 months (12 - 34 months). TR was functional in 87% of cases and was more than moderate in 52% of cases. Mean RA strain was 18,7 ± 11,2%, and divided patients in low strain (LS) and high strain (HS). HS was associated with lower increase and frequently a decrease in DD (-5,5 ± 44,7 mg vs 20,8 ± 63,2 mg, p = 0,009) but no echocardiographic variable independently predicted an increase in DD. Patients with worsening renal function had significantly lower RA (16.7 ± 10.6% vs 20.7 ± 10.9%, p 0.042). LS independently predicted a worsening renal function (OR 3,07; 95% CI 1,026-9,2). RA strain was significantly lower in hospitalized patients (13.1 ± 8 vs 20.3 ± 11.4, p<0.001). Cox regression analysis showed a LS to be an independent predictor of the composite endpoint (adjusted HR 3.1, 95% CI 1.101 – 8.74) correcting for other clinical and echocardiographic variables. ROC curve analysis showed an RA strain cut-off of 18.5% to have a sensitivity of 79% and specificity of 56% in predicting the combined endpoint. Conclusions RA strain is associated with DD and LS patients have higher DD at follow up. RA strain is an independent predictor of worsening renal function. RA function measured by strain is an independent predictor of the composite endpoint of death and/or hospitalization.

Prognostic role of right atrial strain in patients with secondary tricuspid regurgitation: insights from the CARE-TR registry

Abstract Background Recently, right atrial (RA) deformation evaluated with speckle tracking echocardiography has emerged as prognostic parameter in patients with pulmonary hypertension and tricuspid regurgitation (TR). Purpose To explore the prognostic role of right atrial reservoir strain (RASr) in patients atrial and ventricular secondary TR (ASTR; VSTR). Methods The Consecutive pAtients with seveRE Tricuspid Regurgitation evaluated in heart failure (HF) and Valve Clinics (CARE-TR) registry collected data from patients with at least severe TR enrolled at 3 Italian Centres between January 2020 and December 2022. The present analysis includes 402 patients with STR and complete data on right atrial function. Patients were classified as ASTR in presence of all the following echocardiographic parameters: left ventricular ejection fraction ≥ 50%, pulmonary artery systolic pressure ≤ 50 mmHg, right ventricular (RV) mid end-diastolic diameter (RVEDD) ≤ 38 mm and/or RV end-diastolic area ≤ 13 cm2/m2, RV fractional area change ≥ 35% and/or RV free wall longitudinal strain (RVFWLS) ≥ 17%. Right atrial indexed volume (RAVI) and RASr were collected. The lack of at least one of these parameters identified the VSTR aetiology. The study endpoint was a composite of all-cause mortality and heart failure hospitalization at 18-months follow-up. Results Patients’ median age was 79 years (IQR 72-83) and 45% were male. At 18-months follow-up, 139 patients (46%) reached the primary endpoint. After adjustment for age, male sex, glomerular filtration rate (GFR), New York Heart Association (NYHA) class, RAVi and loop diuretic dose, RASr was the only independent predictor of events in patients with ASTR (HR 0.91, 95% CI 0.86-0.96, p = 0.001); in patients with V-FTR after adjustment for age, male sex, coronary artery disease, GFR, NYHA class, loop diuretic dose and RAVi, RVEDD (HR 1.04, 95% CI 1.01-1.07, p = 0.029) and RVFWLS (HR 1.07, 95% CI 1.01-1.12, p = 0.049) were the only echocardiographic parameters associated with poor prognosis, while RASr was not. At receiver operating characteristic analysis, the best cut-off of RASr to predict the composite outcome in the whole population was 12% (sensitivity 74%, specificity 70%, area under the curve [AUC] 0.75, p < 0.001). Cumulative survival free from events was lower in patients with RASr ≤ 12% as compared to those with RASr > 12% in the whole population (52% vs 84%; Log rank p < 0.001) and in both ASTR and VSTR (Figure 1 and Figure 2). Conclusions Right atrial reservoir strain is an useful and reliable tool to identify patients with STR at high risk of death and hospitalization for heart failure and it offers the best prognostic performance in patients with ASTR. ASTR patients survival according to RASr VSTR patients survival according to RASr

Prediction of mortality and heart failure admission with the mitraScore after percutaneous mitral valve repair: an external validation study

Abstract Background Prediction of events is critical in decision-making for transcatheter edge-to-edge mitral valve repair (TEER). A new score has been reported for this aim, the MitraScore, that showed adequate performance for predicting death and heart failure rehospitalization in an external validation cohort described in the original publication. Purpose Our aim was to perform an external validation of this prognostic score in an independent sample. Methods The MitraScore assigned 1 point to each independent predictor of mortality found in the validation cohort: age ≥75 years, anemia, glomerular filtrate rate <60 mL/min/1.73 m2, left ventricular ejection fraction <40%, peripheral artery disease, chronic obstructive pulmonary disease, high diuretic dose, and no therapy with renin-angiotensin inhibitors. We calculated the MitraScore in every subject of a prospective cohort of patients treated with TEER in a single institution from November 2011 to January 2024. Association of the score with mortality and the combined end-point of heart failure admission or death was assessed by the Cox proportional hazard method and Kaplan Meier curves. Discrimination was studied by receiver operating characteristics (ROC) curve. Results A total of 191 consecutive patients (median age [p25-75] 74 [64-80] years, 33% female) were included in the study. Our sample differed significantly from the original derivation and validation cohorts in several baseline variables (figure 1). After a median follow up of 24 [9-50] months, 92 patients (48.4%) had 160 admissions for heart failure and 73 patients died (38.2%). MitraScore, as a continuous variable, had a significant association with mortality and the combined end-point in follow-up, either by univariate Cox analysis (HR 1.36 [1.11-1.66] per each score point, p=0.003 for all-cause mortality, and HR 1.35 [1.11-1.65] per each score point, p=0.003 for the combined end-point), and Kaplan Meier analysis (figure 2). Discrimination by ROC analysis was nearly significant for both end-points (C statistics 0.58 [0.50-0.67], p=0.052 for all-cause mortality, and HR 0.58 [0.49-0.66], p=0.068 for the combined end-point). Conclusion The MitraScore, considered as a continuous variable, was significantly associated with mortality and the combined end-point of heart failure admission or death in follow-up in the present external validation study. These data support the use of this prognostic index in risk stratification for patients treated with TEER.

Right ventricular function and pulmonary coupling in relation to loop diuretic resistance in patients with congestive heart failure

Abstract Background Right ventricular (RV) dysfunction has been proven to be a prognostic factor among heart failure (HF) patients. Loop diuretic resistance (LDR) is associated with worse clinical outcomes, greater symptom burden and mortality. Limited data exist to characterise the relation between RV and kidney function, especially LDR. Purpose To assess relationship of different echocardiographic RV function parameters with loop diuretic resistance in patients with congestive HF exacerbation. Methods Consecutive patients with congestive HF exacerbation were prospectively included in the study. LDR was defined as persistent congestion on the 4th day of hospital stay despite high i.v. loop diuretic dose. Transthoracic echo with detailed assessment of right heart geometry and function, clinical and biochemical parameters were evaluated on the 1st and 4th day of hospital stay. A TAPSE/PASP ratio was used to assess RV to pulmonary circulation coupling. Results are presented as mean±standard deviation or median (interquartile range). Results 40 patients were included in the study with median age 84 (72,8; 86) years, mean left ventricle ejection fraction (EF) 37.3±13.0 %, mean E/e’ 18.6±5.0, median NT-proBNP 8967.5 (3024; 15241) pg/ml. LDR was found in 14 (35%) patients. Univariate analysis identified the following risk factors for LDR: pulmonary artery systolic pressure (PASP), right ventricle to pulmonary circulation coupling index (TAPSE/PASP ratio), serum creatinine concentration, serum urea concentration, serum low-density cholesterol (LDL) concentration (results are shown in the table). TAPSE/PASP on admission correlated negatively with NT-pro BNP (r -0.44 , p=0.007) and positively with diuresis/40mg of furosemide (r 0.38, p=0.02). In the multivariable model, the significant negative relationship between LDR and TAPSE/PASP (beta coefficient -0.653, p= 0.047) as well as LDL (beta coefficient -0.055, p=0.043) was observed. Conclusions TAPSE/PASP, one of the most significant non-invasive indexes of RV failure, assessed at admission might be a clinically relevant marker of LDR in patients with congestive HF exacerbation. Study group characteristics

Factors Determining the Need for Ultrafiltration in Cardiorenal Syndrome

This study investigates the factors determining the need for ultrafiltration (UF) in patients with cardiorenal syndrome presenting with hypervolemia-related symptoms and signs. A total of 88 patients hospitalized for hypervolemia were treated according to current guidelines, with UF employed as a rescue therapy when diuretic treatment failed to achieve adequate decongestion. Data collected included medical history, laboratory findings, blood pressures, diuretic doses, spot urine sodium (measured 6 hours after diuretic therapy), response to diuretics, postdischarge creatinine levels, rehospitalization rates, and mortality rates. UF was required in 23.90% of patients due to insufficient response to diuretics, with a higher rate observed in men (34.10%) compared with women (13.64%). Patients needing UF had lower systolic blood pressure, higher initial serum creatinine levels, and elevated pro-B-type natriuretic peptide levels. Statistical analysis showed that an increase in initial creatinine levels raised the risk of requiring UF by 6.443 times, while a one-unit decrease in urine sodium increased the risk by 1.037 times. These findings suggest that male gender, high pro-B-type natriuretic peptide levels, low spot urine sodium, low systolic blood pressure, and high initial creatinine levels may predict the need for UF. Further research involving larger patient cohorts is necessary to refine these criteria and develop a risk score.

Canagliflozin reduces oral loop diuretic intensification in patients with type 2 diabetes: A participant-level pooled analysis of the CANVAS and CREDENCE trials.

The sodium-glucose cotransporter 2 inhibitor canagliflozin reduces the risk of heart failure (HF) hospitalization or cardiovascular death and chronic kidney disease (CKD) progression among patients with type 2 diabetes at high cardiovascular risk or with CKD. Patients with type 2 diabetes commonly have coexisting HF or CKD that require treatment with loop diuretics; however, the prognostic implications of oral loop diuretic intensification are not well characterized. In this participant-level pooled analysis of the CREDENCE and CANVAS trials (not including CANVAS-R), 1454/8731 (16.7%) patients were treated with loop diuretics at baseline. Over a median on-treatment follow-up of 2.2 years, 1264 patients (14.5%) required oral loop diuretic intensification, of whom 981 (77.6%) required initiation of oral loop diuretics and 283 (22.4%) required oral loop diuretic dose increase. Patients requiring oral loop diuretic intensification experienced rates of subsequent HF hospitalization, CKD progression and mortality that were 29.5-, 5.0-, and 3.5-fold higher, respectively, than those not requiring oral loop diuretic intensification. Treatment with canagliflozin reduced the need for oral loop diuretic intensification by 41% (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.53-0.66) including both new diuretic initiation (HR 0.65; 95% CI 0.57-0.74) and diuretic dose increase (HR 0.42; 95% CI 0.33-0.54). Inclusion of oral diuretic intensification in an expanded HF composite outcome inclusive of cardiovascular death and HF hospitalization approximately double the number of events, with similar observed treatment effect (HR 0.64; 95% CI 0.58-0.70). Among high-risk patients with type 2 diabetes, new oral loop diuretic intensification was frequent and portended adverse prognostic significance. Treatment with canagliflozin significantly reduced the need for loop diuretic intensification. CANVAS (Canagliflozin Cardiovascular Assessment Study), ClinicalTrials.gov NCT01032629; CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation), ClinicalTrials.gov NCT02065791.

Utility of loop diuretics as a marker of risk in clinical trials of heart failure with preserved ejection fraction: Analysis from the Swedish Heart Failure Registry.

It is common in heart failure (HF) trials, especially in HF with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF), to select for increased risk of outcomes ('enrichment'). We investigated the association between loop diuretic use and common trial outcomes. Patients in the Swedish HF Registry with HFmrEF and HFpEF were divided into three groups: no loop diuretic use, 1-40 mg furosemide equivalent, and >40 mg. Outcomes were assessed for all patients and high risk for exacerbation patients (previous HF hospitalization [HFH] or N-terminal pro-B-type natriuretic peptide ≥300 ng/L). Among 25 986 patients, 41.3% were not taking loop diuretics, 33.5% had 1-40 mg, and 25.2% had >40 mg; 80.7% were at high risk. With increasing diuretic dose, the crude risk of all outcomes increased in both analysis groups. Event rates for cardiovascular death (CVD)/HFH were as follows for total: no loop diuretic: 6, dose 1-40 mg: 17, dose >40 mg: 34 and as follows for high risk: no loop diuretic: 8, dose 1-40 mg: 19, dose >40 mg: 36. Hazard ratios (HRs) for CVD/HFH with no loop diuretic as reference for the total population were: 1-40 mg HR 2.59, >40 mg HR 4.91 (all p < 0.001), and for high risk were: 1-40 mg HR 2.21, >40 mg HR 4.05 (all p < 0.001). In HFpEF and HFmrEF, loop diuretics were used in 58.7% of patients. Use of and higher doses were strongly associated with HF trial-relevant outcomes. These associations were similar regardless of other risk markers. In HFpEF/HFmrEF trials, requiring loop diuretics as an enrichment factor will reduce the number of eligible patients but increase event rates considerably.

Peripheral Venous Pressure-Guided Decongestive Therapy in Heart Failure 2 (PERIPHERAL-HF2).

Congestive symptoms are the primary cause of hospitalizations in heart failure (HF), and diuretics remain the cornerstone of their management. However, clinical practice varies widely due to a lack of a reliable measure of congestion guiding diuretic use. Consequently, many HF patients are discharged prematurely without adequate decongestion, leading to increased readmissions and mortality. Peripheral venous pressure (PVP) has emerged as a promising non-invasive measure of vascular congestion. This study will enroll 650 patients aged 18-99 years admitted with de novo or acutely decompensated chronic HF. In the standard care arm, diuretic dosing and discharge decisions will be at the physician's discretion. In the PVP-guided arm, the goal is to maintain a PVP of <9 mmHg, with diuretic dosing adjusted based on daily PVP changes and urine output. The primary outcome is a composite of all-cause mortality, hospitalizations, and emergency department visits, with secondary outcomes including cardiovascular mortality and HF-related readmissions. We hypothesize that PVP-guided diuretic therapy will provide more precise and effective decongestion than standard care, reducing rehospitalizations and mortality. In conclusion, this study will offer valuable insights into the relationship between diuretic therapy, vascular congestion, and cardiac and renal outcomes. Trial registration: ClinicalTrials.gov Identifier: NCT06495892.

Comparative efficacy of different drugs in acute heart failure with renal dysfunction: a systematic review and network meta-analysis.

This network meta-analysis was to compare the efficacy of different drugs on cardiac function, renal function, and clinical outcomes in patients with acute heart failure (AHF) accompanied by renal dysfunction. PubMed, EMBASE, Cochrane Library, and Web of Science were searched to screen all clinical trials of AHF between January 1st 2001 and March 31th 2024. The primary outcome measures were N-terminal pro-B type natriuretic peptide (NT-proBNP), B-type natriuretic peptide (BNP), glomerular filtration rate (GFR), blood urea nitrogen, serum creatinine, all-cause mortality within 60 days, and cardiovascular mortality. After screening 30,697 citations, 13 studies (21,745 patients) were included, and drugs including nesiritide, dopamine, tolvaptan, levosimendan, dobutamine, furosemide, and spirolactone, and high dose of diuretics (HDD, furosemide, and spirolactone) were estimated. The results indicated that HDD had the best efficacy in reducing NT-proBNP levels. In detail, HDD notably reduced NT-proBNP levels compared to conventional treatment or placebo (PLC) [MD = -950.24; 95% CrI (-1,832.21, -64.12)]. Levosimendan significantly increased GFR levels compared to PLC [MD = 14.46; 95% CrI (3.88, 25.97)] and tolvaptan [MD = 13.83; 95% CrI (2.31, 25.33)]. No significant difference was found in 60-day all-cause mortality and cardiovascular mortality across drugs. HDD showed the best efficacy in reducing NT-proBNP levels compared with dopamine and nesiritide, and levosimendan could significantly improve GFR levels, with no marked difference in the effect of various drugs on 60-day all-cause mortality. Hence, HDD and levosimendan may be optimal agents in the treatment of AHF with renal dysfunction. PROSPERO, identifier (CRD42023454616).

Importance of early use of tolvaptan in hyponatremic acutely decompensated heart failure patients, a retrospective study

BackgroundHyponatremia is one of the complicating findings in acute decompensated heart failure. Decrease in cardiac output and systemic blood pressure triggers activation of renin–angiotensin–aldosterone system, antidiuretic hormone, and norepinephrine due to the perceived hypovolemia. Fluid-overloaded heart failure patients are commonly treated with loop diuretics, acutely decompensated heart failure patients tend to be less responsive to conventional oral doses of a loop diuretic, while other different diuretics could work in different part of nephron circulation system. In this study, we aim to further examine the role of tolvaptan, a vasopressin receptor antagonist, in the treatment of hyponatremia secondary to acutely decompensated heart failure.ResultsA total of 71 patients with hyponatremia secondary to ADHF were included, and all patients were given tolvaptan. 37 patients were administered tolvaptan early (up until 5 th day of admission). 34 patients received tolvaptan after 5 th day of admission mean administration as 6.86 th day, and median administration was 5 th day. Analysis showed lower length of stay in patients receiving early administration of tolvaptan compared to late administration (8.86 ± 5.06 vs 18.5 ± 9.05 p0.001, respectively). Patients with early initiation of tolvaptan also achieved a larger net increase in sodium levels at discharge compared to admission (6.46 ± 6.69 vs 3.68 ± 4.70 p0.048, respectively).ConclusionsEarly administration of tolvaptan in treating hyponatremia in acutely decompensated heart failure patients is associated with a lower length of hospitalization and a higher increase in serum sodium of patients in hyponatremic ADHF patients.

Examining Symptom Management and Quality of Life of Loop Diuretic-Induced Overactive Bladder Among Heart Failure Patients: Physician and Patient Perspectives

Loop diuretics are strongly recommended in patients with chronic congestive heart failure (HF) to alleviate signs and symptoms of fluid overload. Loop diuretics help relieve congestive symptoms and reduce mortality, but may have side effects. This survey study examined the impact of loop diuretic-induced overactive bladder (LD-OAB) symptoms on quality of life (QOL) in HF patients; and management of OAB by HF patients and physicians. We found that (1) HF patients noted less severity of symptoms but similar QOL with non-HF. (2) HF patients (58.8%) self-managed and underreported symptoms to physicians compared to non-HF (74.8%); accordingly 65% of physicians noticed and managed symptoms. (3) Patients used mechanical solutions (pads/diapers, Kegel exercises, and fluid reduction), and physicians adjusted diuretic doses or prescribed medications for OAB. Our study highlighted that HF patients' QOL associated with bladder symptoms was not better than the non-HF group despite milder symptoms. Many HF patients either did not report or coped with/self-managed their loop diuretic-induced bladder symptoms, pointing to a need for better awareness of patient experiences and patient-physician communication.

Racial differences in diuretic therapy, B-type natriuretic peptide values, and prognosis in acute heart failure.

Whether variability of B-type natriuretic peptide (BNP) values between races affects its clinical integration as a marker for congestion and predictor of prognosis in acute heart failure (AHF) remains unknown. We aimed to investigate the relationship between diuretic therapy, change in BNP value, and prognosis in AHF in relation to racial differences. This analysis combined data from the AKINESIS and REALITY-AHF studies. We included White, Black, and Asian individuals admitted with AHF requiring intravenous diuretic therapy. We examined the relative change in BNP values at 48 h post hospital admission, and its association with diuretic therapy and one-year mortality. Of 1380 participants, 29 % were White, 12 % were Black, and 58 % were Asian. Admission BNP values were highest in Black, followed by Asian and White individuals. After adjusting for confounding factors, Black individuals had significantly higher admission BNP values compared to White individuals. During the first 48 h of hospitalization, Asian individuals received the lowest diuretic dose but demonstrated the greatest diuretic response and BNP decrease. After adjustment for confounding factors, Asian individuals were more likely to have a BNP decrease compared to White individuals. Higher admission BNP values predicted higher one-year mortality in White and Asian but not in Black individuals (p for interaction = 0.021). BNP decrease was associated with a lower one-year mortality without a significant interaction by race. In AHF patients, admission BNP was higher in Black, and its decrease after diuretic therapy was greater in Asian individuals. A BNP decrease predicted a better prognosis, regardless of race.

Gender differences in efficiency of the telemedicine care of heart failure patients. The results from the TeleEduCare-HF study

IntroductionThe aim of this study was to implement a model of healthcare for patients with heart failure (HF) and to assess the differences between men and women in the study population.Material and methodsThrough care and an extensive educational panel (dietary recommendations, physical activity, titration of diuretics, psychological support), emphasis was placed on prevention. All patients had a baseline cardiology consultation with recommendations regarding treatment, self-care, diet, and exercise. Based on regular measurements of weight and blood pressure HF patients were telemonitored by nurses, primary care physicians and referred to cardiologists when necessary. The questionnaire was conducted in all patients at baseline after enrollment to the study and after 3 months of telemonitoring and extensive educational process.ResultsThe study finally included 140 men with an average age of 66 years (SD: 56–71) and 163 women with an average age of 64 years (58–72). The ischemic origin of HF was present in 78% of men and 73% of women (p = 0.40), and 31% of men and 16% of women declared myocardial infarction in the past (p = 0.002). Men more often survived sudden cardiac arrest (7.8% vs. 1.2%; p = 0.004) and had implantable cardiac devices compared to women (16% vs. 3%; p = 0.001). Male patients reported significantly more often alcohol consumption, smoking, and less frequently any physical activity. Women significantly more often than men suffered from cancer, depression, and thromboembolic events and less frequently from obstructive sleep apnea. The mean left ventricular ejection fraction (LVEF) was 43% (SD: 30–58) for men, and 57% (45–63) for women (p = 0.0001), and women suffered mainly from heart failure with preserved ejection fraction. There were no differences between genders regarding the number of hospitalizations in last 12 months. The men, despite lower LVEF, felt short of breath/tired when climbing the stairs up than women (3 [2–4] vs. 2 floors [1–3]; p = 0.001), had higher distance in meters when walking on flat ground (400 [200–400] vs. 300 m [100–400]; p = 0.0001), and less frequently had to get up to go to the toilet at night (p = 0.03). Men also suffered significantly less often from shortness of breath at rest, swelling of the lower limbs and shortness of breath that wakes them up at night. Only 35% of men and 19% of women had HF self-care training, and only 35% of men and 46% of women knew how to increase the dose of diuretic on their own if shortness of breath or swelling increases. Based on the EuroQol-5 dimensions 5-levels questionnaire, significantly more women than men reported moderate and serious problems with moving around, serious problems with performing ordinary activities independently as well as moderate and serious pain problem and a significant level of anxiety. Men more often than women reported serious problems with self-care.ConclusionsWomen suffer more often from HF symptoms and have worse quality of life assessed in EQ-5D-5L than men despite their higher LVEF.

Design and rationale of the eLym™ System for Decompensation of Excess Lymphatic Fluid via the Thoracic Duct in Acute Heart Failure (DELTA‐HF)

AbstractAimsThe interstitial space is the major compartment in which the excess fluid is located, forming peripheral congestion in acute decompensated heart failure (ADHF). The lymphatic system is responsible for the constant drainage of the compartment. In ADHF, the inefficiency of this system causes extravascular fluid accumulation, underscoring the crucial role of lymphatic system failure in ADHF's pathophysiology. The eLym™ System is a transcutaneous device designed to facilitate lymph drainage by creating a low‐pressure zone in the thoracic duct area, theoretically allowing more efficient decompression of the lymphatic system.Methods and ResultsThe safety and feasibility of the eLym™ System for the Decongestion of Excess Lymphatic Fluid via the Thoracic Duct in Acute Decompensated Heart Failure: DELTA‐HF Study is a prospective, multicentre, single‐arm study designed to evaluate the safety and feasibility of the WhiteSwell eLym™ System in the treatment of fluid overload in ADHF. A maximum of 50 subjects may be enrolled and undergo the treatment. Inclusion criteria include the presence of congestion, a home diuretic dose ≥80 mg furosemide (or equivalent) and elevated natriuretic peptides. The key exclusion criteria include anatomical abnormalities and the inability to undergo systemic anticoagulation. The study endpoints include the safety (short‐ and long‐term) and feasibility of the procedure. Several congestion indexes will be prospectively assessed. Descriptive statistics will summarize the study results. The study was registered in clinicaltrial.gov (NCT05747196).ConclusionsThe results of the DELTA‐HF study will provide information about the safety and feasibility of the eLym™ System and will provide first‐in‐human clinical signals of its use in ADHF patients.

A Systematic Review and Meta-Analysis of an Angiotensin Receptor-Neprilysin Inhibitor in Patients Using a Durable Left Ventricular Assist Device.

Introduction: Sacubitril/valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) drug used to treat patients with heart failure and has shown improvement in outcomes. Different studies reported the use of an ARNI in patients using left ventricular assist devices (LVADs). However, there are limited data on the use of ARNIs in this population. We aimed to assess the efficacy of ARNIs in LVAD patients. Methods: A systematic search was performed in PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to November 2024. We used all relevant words for "ARNI" and "LVAD" to search, and we included studies that assessed ARNIs in patients with LVAD. Efficacy and safety outcomes were extracted from the included studies. R software version 4.4.2 was used for a meta-analysis. Results: Seven studies totaling 249 patients were included. The ARNI was found to be effective in improvements from baseline in the New York Heart Association (NYHA), B-type natriuretic peptide (BNP) (mean = -630.07 pg/mL, 95% CI [-1113.13, -147.01]), diuretic dose (furosemide equivalents) (mean= -76.05 mg/day, 95% CI [-145.11, -6.99]), left ventricular end-diastolic diameter (LVEED) (mean = -7.3 mm, 95% CI [-11.4, -3.1]), and left ventricular ejection fraction (LVEF) (mean =5, 95% CI [3.52, 6.48]). No improvement was found in the creatinine (Cr) level. However, a slight increase in the potassium level was noticed (mean= 0.17 mEq/L, 95% CI [0.02, 0.34]). The overall mortality in patients using the ARNI was 5%, 95% CI [0.00, 20], and discontinuation was found in 25%, 95% CI [0, 100]. Conclusions: The ARNI improved several cardiac structural and hemodynamic parameters in patients on LVAD support.

Outpatient worsening of heart failure and mortality in transthyretin amyloid cardiomyopathy.

Transthyretin cardiomyopathy (ATTR-CM) is characterized by episodes of worsening heart failure (WHF) which can include heart failure (HF) hospitalizations or urgent unplanned visits for administration of intravenous diuretics. WHF characterized by outpatient intensification of oral loop diuretics is common yet its prognostic implications for ATTR-CM patients relative to other WHF events remains unclear. We assessed how WHF characterized by outpatient diuretic intensification (ODI) relates to mortality in this population. This was a retrospective study of ATTR-CM patients presenting to the Columbia University Irving Medical Center. Oral loop diuretic dose was recorded longitudinally. WHF characterized by ODI was defined as a persistent increase in oral loop diuretic dose lasting >1 month. We analysed the all-cause mortality rate after either WHF event (hospitalization or ODI) relative to subjects who had no WHF event. Overall, 303 patients highly treated with tafamidis were included: 152 (50.2%) patients had no WHF events, 35 (11.6%) experienced HF hospitalization, and 145 (47.9%) experienced ODI; 29 (9.6%) patients experienced both WHF events. Patients experiencing ODI had higher rates of subsequent mortality (17.7 per 100 person-years; 95% confidence interval [CI] 13.3-23.7) as did those with a HF hospitalization (29.8 per 100 person-years; 95% CI 17.7-50.3) than patients without WHF events (5.0 per 100 person-years; 95% CI 3.0-8.3) on log-rank test. WHF characterized by ODI was independently associated with mortality in a model adjusting for age, genotype, atrial fibrillation, disease duration, time-varying tafamidis use and National Amyloid Centre (NAC) or Columbia stages. In contemporary patients with ATTR-CM treated with tafamidis, WHF requiring ODI is prognostic of subsequent mortality and is a clinical marker of disease progression.

Diuretic efficiency of a single dose of subcutaneous versus oral furosemide after heart failure hospitalization across diuretic resistance strata: A pilot randomized controlled trial

AimsDiuretic resistance (DR) in heart failure (HF) is associated with worse outcomes. Furoscix®, a self‐administered subcutaneous (sc) furosemide injection administered via on‐body infusor, is approved for HF congestion relief. However, its efficacy in patients with DR post‐HF hospitalization remains unknown.Methods and resultsIn this open‐label pilot randomized controlled trial, 70 participants were randomized within 14 days post‐HF hospitalization to receive a single dose of 80 mg sc furosemide or home oral dose furosemide. Enrolment was stratified by presence of DR (admission BAN‐ADHF score ≥12) with a 2:1 enrolment of those with versus without DR. Key outcomes included diuretic efficiency, the total urine output per mg of diuretic administered, and peak urine sodium within 8 h of dose administration. Treatment effects were calculated as the difference in estimated marginal means across study groups and DR strata using linear mixed‐effect models. Overall, 70 participants were enrolled (57 years, 27% female, 70% Black, 79% with HF with reduced ejection fraction). Participants with DR (n = 46) had worse kidney function, higher N‐terminal pro‐B‐type natriuretic peptide, and higher home diuretic dose. Among participants with DR, sc furosemide versus oral furosemide led to significantly greater diuretic efficiency (34.0 vs. 22.6 ml/mg, p = 0.002) and peak urine sodium (100 vs. 83 mmol/L, p = 0.029), while participants without DR had similar diuretic efficiency (29.8 vs. 30.1 ml/mg, p = 0.94) and peak urine sodium (96 vs. 95 mmol/L, p = 0.93) across both treatments. DR significantly modified the effect of sc versus oral furosemide on diuretic efficiency (pinteraction: treatment × diuretic resistance = 0.022).ConclusionSingle‐dose sc furosemide was associated with greater diuretic efficiency and peak urine sodium than oral furosemide in participants with DR discharged following recent HF hospitalization.

The Relationship of Diuretics and Dietary Sodium in Patients with Heart Failure: An Analysis of the SODIUM-HF Trial

BackgroundSODIUM-HF was a large clinical trial testing dietary sodium restriction compared to usual care in patients with heart failure that showed no reduction in clinical events. It has been suggested that diuretic doses in response to dietary sodium modification may have influenced the trial results. ObjectiveWe assessed the effects of baseline diuretic dose and diuretic dose changes on clinical outcomes in the SODIUM-HF trial. MethodsDiuretics were converted to furosemide-equivalent diuretic total daily doses. Furosemide dose was treated as a continuous variable and also stratified into 0 mg, 1–39 mg, 40 mg, 41–80 mg, and >80 mg daily. The baseline diuretic dose and change in diuretic dose were assessed and correlated with dietary sodium restriction and changes in dietary sodium intake. We then examined the relationship between diuretic dosing and the primary outcomes of SODIUM-HF (cardiovascular-related emergency department visit, cardiovascular-related hospitalization, and all-cause mortality). ResultsOf the 806 patients enrolled in the SODIUM-HF trial, 784 had known diuretic status at baseline: 209 patients (26.7%) with 0 mg, 134 patients (17%) with 1-39 mg, 205 patients (26.1%) with 40 mg, 118 patients (15.1%) with 41-80 mg, and 118 patients (15.1%) with >80 mg. No correlation was found between dietary sodium intake and diuretic dose, either at baseline or change throughout the study (P>0.05). For the primary outcomes, the 2-year risk of primary outcomes was strongly correlated with diuretic dose at baseline across the overall SODIUM-HF population (P<0.001). No significant association was found between the treatment arm and the risk of primary outcomes, within each baseline diuretic dose range or with change in diuretic dose (both P>0.05). ConclusionsAlthough a higher baseline diuretic dose was associated with worse clinical outcomes, no association was found between dietary sodium restriction, baseline or change in diuretic dose and the primary outcomes.

Patterns of diuretic titration during inpatient management of acute decompensated heart failure.

Hospitalization rates for acute decompensated heart failure (ADHF) have increased, resulting in 6.5 million hospital days annually. Despite this, optimal diuretic strategies for managing ADHF remain unclear, highlighting the need to analyze diuretic practice patterns in ADHF treatment. We performed a retrospective cohort analysis of adults hospitalized for ADHF, regardless of left ventricular ejection fraction (LVEF) between January 1, 2014 and December 21, 2021 at a large, quaternary healthcare system to determine diuretic practice patterns. We performed multivariable regression analyses to assess time to initial, second, and maximum diuretic therapy with hospital length of stay (LOS) and 30-day readmission. Among 4,298 adults admitted for ADHF (mean age 63 years, 62% male, 52% LVEF ≤40%) median time to max diuretic therapy was 1.8 (0.7, 3.8) days. Median time to initial IV loop diuretic dose was 3.6 (2.1, 6.5) hours, while time to second dose of IV loop diuretic dose was 10.2 (6.3, 15.1) hours. Time to initial IV loop diuretic, time to second IV loop diuretic dose, and time to maximum diuretic therapy were all positively associated with increased LOS but were not associated with 30-day readmission. There was wide variation in loop diuretic escalation strategies and use of sequential nephron blockade. There was wide variation in diuretic strategies at a single academic medical center. Increased time to initial IV loop diuretic, time between diuretic doses, and longer time to max diuretic therapy were associated with increased LOS but were not associated with 30-day readmission suggesting different diuretic strategies may affect patient outcomes and warrant dedicated investigation in the future.