High-dose Diuretics Research Articles

Mechanistic Differences between Torsemide and Furosemide.

Torsemide is proposed to have clinically important pharmacokinetic and pharmacodynamic advantages over furosemide. However, clinical outcomes did not differ in the Torsemide Comparison with Furosemide for Management of Heart Failure (TRANSFORM-HF) randomized trial. We conducted a multicenter mechanistic substudy of patients with heart failure randomized to oral furosemide or torsemide (TRANSFORM-Mechanism). At baseline and 30 days, participants underwent detailed assessments of pharmacokinetic and pharmacodynamic parameters. TRANSFORM-Mechanism enrolled 88 participants. Kidney bioavailability, or the proportion of dose delivered to the tubular site of action, was significantly less with torsemide compared to furosemide [median 17.1%, (IQR 12.3, 23.5%) vs. 24.8% (16.6, 34.1%), p < 0.001]. Furosemide had a longer duration of kidney drug delivery and duration of natriuresis (p≤0.004 for both). Prescribed doses of furosemide and torsemide in TRANSFORM-Mechanism were similar to TRANSFORM-HF, with providers on average using a 2:1 dose equivalence conversion between drugs. However, these doses resulted in a substantially greater natriuresis with torsemide (p<0.001). A dose equivalence of ∼4:1 resulted in similar natriuresis. Higher diuretic doses in the torsemide group resulted in mild perturbations in kidney function and significant increases in renin, aldosterone, and norepinephrine (p<0.05 for all). Plasma volume (p=0.52) and body weight (p=0.89) did not improve with torsemide vs. furosemide. We observed no meaningful pharmacokinetic/pharmacodynamic advantages for torsemide vs. furosemide. The greater natriuresis from higher diuretic doses in the torsemide group was offset by greater neurohormonal activation and kidney dysfunction.

What should otolaryngologists know about dural venous sinus stenting?

Dural venous sinus stenting is an emerging and exciting area in otolaryngology in collaboration with neurosurgeons and neuroradiologists. The first cases were reported 20 years ago. It is now considered part of the routine treatment of increased intracranial pressure due to transverse sinus stenosis. ENT doctors are the first to see these patients in their clinics, as sinus headaches, pulsating tinnitus, and dizziness are the most common symptoms. Previously, with limited success, high-dose diuretics and intracranial shunts had been the only options for treating these patients. Other methods, such as covering the sigmoid sinuses with graft material, appear to cause a sudden increase in intracranial pressure that can lead to blindness and even death. This overview summarizes the clinical and imaging characteristics of patients who will benefit from endovascular sinus stenting for elevated intracranial pressure.

CASE OF MANAGING POSTPARTUM HYPERTENSION IN BREASTFEEDING WOMEN IN PRIMARY CARE

Postpartum hypertension requires careful management, particularly in breastfeeding women, to prevent complications like eclampsia and future cardiovascular issues. This case involves a 40-year-old Southeast Asian woman, G3P3, who presented at a primary care clinic for a 6-week postnatal check-up. The patient, with a history of gestational hypertension, managed with labetalol during pregnancy, reported elevated blood pressure (average 140/90 mmHg) while breastfeeding. Postpartum management initially included nifedipine, which was tapered due to concerns about drug transfer into breast milk. Her blood pressure was 145/95 mmHg at the clinic without significant symptoms. Guidelines suggest that beta blockers like labetalol, propranolol, metoprolol, and calcium channel blockers like nifedipine and verapamil have minimal transfer into breast milk and are generally safe. Caution is advised with atenolol and acebutolol due to higher transfer levels. ACE inhibitors like enalapril are considered safe but require monitoring of infant hemodynamics. High-dose diuretics may reduce milk production and are typically avoided. In managing postpartum hypertension in breastfeeding women, it is crucial to balance maternal health needs with infant safety. The use of antihypertensive agents with the lowest transfer into breast milk is recommended. International guidelines suggest a multidisciplinary approach involving pediatricians to monitor and ensure the well-being of both mother and infant. Individualized care and adherence to current guidelines are essential in these cases.

Sequential Blockade with Loop Diuretics and Acetazolamide: A Novel Strategy in Acute Heart Failure

Abstract Acute decompensated heart failure (HF) is the most common form of acute HF (AHF) and presents with systemic congestion due to left ventricular dysfunction with sodium and water retention. Diuretics are the mainstay of treatment for AHF, with loop diuretics being the first-line therapy. However, in some studies, patients who were given high doses of loop diuretics were discharged from the hospital with residual signs of volume overload. Combining acetazolamide, a carbonic anhydrase inhibitor, with loop diuretics has been shown to be beneficial as it increases the efficacy of loop diuretics and reduces the signs and symptoms of congestion. Further, it can be used for the prevention or treatment of diuretic resistance (DR). Sequential nephron blockade with acetazolamide has emerged as a novel strategy for the treatment of AHF to enhance the efficacy of loop diuretics and prevent DR. This review highlights the combination of acetazolamide with loop diuretics as an alternative and possibly more effective decongestive strategy option in AHF patients. Nevertheless, there is limited evidence to support this combination therapy, and further research is necessary to substantiate its use in AHF patients.

Phenotype and outcomes according to loop diuretic use in pulmonary arterial hypertension.

The use of loop diuretics in pulmonary arterial hypertension (PAH) is less frequent compared with heart failure. The clinical and prognostic characteristics of PAH patients according to loop diuretic use remain unexplored. In this study, we retrospectively analysed the characteristics and survival of PAH patients requiring different doses of loop diuretics. Patients diagnosed with PAH between 2001 and 2022 at seven European centres for the management of PAH. According to the median equivalent dose of furosemide in the overall cohort, patients were divided into two subgroups: no/low-dose loop diuretic and high-dose loop diuretic. Primary outcome was 5year all-cause mortality. Among the 397 patients included, 227 (57%) were treated with loop diuretics. Median daily furosemide equivalent dose was 25mg, and accordingly patients were divided in no/low dose (i.e. ≤25mg, n=257, 65%) vs. high dose (i.e. >25mg, n=140, 35%). Patients in the high-dose group were older, more likely to have comorbidities, and had a more severe disease according to the ESC/ERS risk category. Crude 5year survival was significantly shorter in patients in the high-dose group, but after adjustment for age, sex, and risk category, high loop diuretic dose was not significantly associated with the primary outcome. Use of high dose of loop diuretics in PAH is associated with a higher burden of comorbidities, more severe disease, and worse survival. However, in PAH, the need of high loop diuretic dose is a marker of disease severity and not an independent prognostic factor.

CARDIOVASCULAR TOXICITY IN METASTATIC PROSTATE CANCER TREATMENT: BALANCING RISKS, TREATING CONSEQUENCES

Abstract Introduction Enzalutamide inhibits the receptor of androgen hormones. It is administered for treating metastasized prostate cancer. Enzalutamide is known to have a cardiotoxic effect. Case Report A 76 year–old man on–treatment for hypertension and overall good health underwent radical prostatectomy and bilateral ileo–obturator lymphadenectomy in 2021 for prostate cancer. In July 2023, infiltrated lymph node and lung/bone metastases were identified. Therefore, oncologist started Enzalutamide administration, i.e. Androgen Deprivation Therapy. Ecocardiography before therapy showed no alterations in cardiac morphology with normal left ventricle ejection fraction (LVEF). Three months after Enzalutamide administration, he experienced worsening dyspnea and peripheral lower extremity edema. He was admitted to the emergency Department of our hospital due to worsening dyspnea at rest, diffuse crackles and increased values in brain natriuretic peptide (BNP, 3203 pg/mL) and troponins. He was transferred to Intensive Care Unit for acute heart failure. Instrumental findings: 2D ECHOCARDIOGRAPHY: LVEF ∼20%, marked global hypocontractility at strain evaluation (GLS –9.3%); LUNG ULTRASOUND: abundant bilateral basal pleural effusion on the right extending to the middle field with atelectasis of the contiguous parenchyma; 24h Holter ECG: frequent supraventricular and ventricular ectopic arrhythmias. He begins non–invasive ventilation (NIV), high–dose diuretics, and Levosimendan. We observed amelioration in symptoms, reduction in pleural effusion, peripheral edema, and BNP levels (from 3203 pg/ml to 468.6 pg/ml). We proceed with weaning from NIV by monitoring respiratory function and performance by means of blood gas analysis. Amelioration in congestion status was evaluated by bioimpedance. After clinical stabilization, coronary angiography was performed which highlighted a bi–vessel obstructive coronary artery disease (long critical stenosis, ∼80%, on the proximal–middle section of the left anterior descending artery, ∼70% at middle section of circumflex and proximal section of first margianl). Therefore, revascularization by PCI plus DES was performed on proximal–middle LAD and on CX–MO1. Patient was discharged soon after in stable condition and underwent outpatient follow–up. Conclusions Enzalutamide might provoke important cardiotoxic effects. It might induce acute cardiac impairment and/or coronary artery diseases. Further analysis and evaluations should be performed.

N-terminal pro-B-type natriuretic peptide post-discharge monitoring in the management of patients with heart failure and preserved ejection fraction-a randomized trial: The NICE study.

There is a lack of specific studies assessing the impact of natriuretic peptide monitoring in the post-discharge management of patients with heart failure (HF) and preserved ejection fraction (HFpEF), throughout the vulnerable phase following acute HF hospitalization. The NICE study aims to assess the clinical benefit of incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) into the post-discharge management of HFpEF patients. Individuals admitted with HFpEF (left ventricular ejection fraction >50%) were included in a multicentre randomized controlled study employing an open-label design with event blinding (NCT02807168). Upon discharge, 157 patients were randomly allocated to either NT-proBNP monitoring (n = 79) or no access to NT-proBNP (control group, n = 78) during pre-scheduled visits at 2, 4 and 12 weeks. Clinical endpoints were evaluated at 6 months. The primary endpoint of HF rehospitalizations occurred in 12.1% patients, without significant differences observed between the NT-proBNP monitoring group (12.8%) and the control group (11.4%) (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.47-2.81, p = 0.760). Regarding secondary endpoints, the NT-proBNP monitoring group demonstrated a significantly lower risk of death (1.3% vs. 10.1%; HR 0.12, 95% CI 0.02-0.98; p = 0.048), whereas non-HF hospitalizations (12.8% vs. 19.0%, p = 0.171) and any adverse clinical event (26.9% vs. 36.7%, p = 0.17) did not reach statistical significance [Correction added on 29 April 2024, after first online publication: In the preceding sentence, "95% CI 0.02 - 0.09" has been corrected to "95% CI 0.02 - 0.98; p = 0.048" in this version.]. Awareness of NT-proBNP levels were associated with higher doses of diuretics and renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers) in the NT-proBNP monitoring group. Post-discharge monitoring of NT-proBNP in HFpEF patients did not exhibit an association with reduced rates of HF hospitalization in this study. Nonetheless, it appears to enhance global clinical management by optimizing medical therapies and contributing to improved overall survival.

Serial direct sodium removal in patients with heart failure and diuretic resistance.

Loop diuretics may exacerbate cardiorenal syndrome (CRS) in heart failure (HF). Direct sodium removal (DSR) using the peritoneal membrane, in conjunction with complete diuretic withdrawal, may improve CRS and diuretic resistance. Patients with HF requiring high-dose loop diuretics were enrolled in two prospective, single-arm studies: RED DESERT (n = 8 euvolaemic patients), and SAHARA (n = 10 hypervolaemic patients). Loop diuretics were withdrawn, and serial DSR was utilized to achieve and maintain euvolaemia. At baseline, participants required a median 240 mg (interquartile range [IQR] 200-400) oral furosemide equivalents/day, which was withdrawn in all participants during DSR (median time of DSR 4 weeks [IQR 4-6]). Diuretic response (queried by formal 40 mg intravenous furosemide challenge and 6 h urine sodium quantification) increased substantially from baseline (81 ± 37 mmol) to end of DSR (223 ± 71 mmol, p < 0.001). Median time to re-initiate diuretics was 87 days, and the median re-initiation dose was 8% (IQR 6-10%) of baseline. At 1 year, diuretic dose remained substantially below baseline (30 [IQR 7.5-40] mg furosemide equivalents/day). Multiple dimensions of kidney function such as filtration, uraemic toxin excretion, kidney injury, and electrolyte handling improved (p < 0.05 for all). HF-related biomarkers including N-terminal pro-B-type natriuretic peptide, carbohydrate antigen-125, soluble ST2, interleukin-6, and growth differentiation factor-15 (p < 0.003 for all) also improved. In patients with HF and diuretic resistance, serial DSR therapy with loop diuretic withdrawal was feasible and associated with substantial and persistent improvement in diuretic resistance and several cardiorenal parameters. If replicated in randomized controlled studies, DSR may represent a novel therapy for diuretic resistance and CRS. RED DESERT (NCT04116034), SAHARA (NCT04882358).

Diuretic Strategies in Acute Decompensated Heart Failure: A Narrative Review.

Heart failure is a common condition with considerable associated costs, morbidity, and mortality. Patients often present to hospital with dyspnea and edema. Inadequate inpatient decongestion is an important contributor to high readmission rates. There is little evidence concerning diuresis to guide clinicians in caring for patients with acute decompensated heart failure. Contemporary diuretic strategies have been defined by expert opinion and older landmark clinical trials. To present a narrative review of contemporary recommendations, along with their underlying evidence and pharmacologic rationale, for diuretic strategies in inpatients with acute decompensated heart failure. PubMed, OVID, and Embase databases were searched from inception to December 22, 2022, with the following search terms: heart failure, acute heart failure, decompensated heart failure, furosemide, bumetanide, ethacrynic acid, hydrochlorothiazide, indapamide, metolazone, chlorthalidone, spironolactone, eplerenone, and acetazolamide. Randomized controlled trials and systematic reviews involving at least 100 adult patients (> 18 years) were included. Trials involving torsemide, chlorothiazide, and tolvaptan were excluded. Early, aggressive administration of a loop diuretic has been associated with expedited symptom resolution, shorter length of stay, and possibly reduced mortality. Guidelines make recommendations about dose and frequency but do not recommend any particular loop diuretic over another; however, furosemide is most commonly used. Guidelines recommend that the initial furosemide dose (on admission) be 2-2.5 times the patient's home dose. A satisfactory diuretic response can be defined as spot urine sodium content greater than 50-70 mmol/L at 2 hours; urine output greater than 100-150 mL/h in the first 6 hours or 3-5 L in 24 hours; or a change in weight of 0.5-1.5 kg in 24 hours. If congestion persists after the maximization of loop diuretic therapy over the first 24-48 hours, an adjunctive diuretic such as thiazide or acetazolamide should be added. If decongestion targets are not met, continuous infusion of furosemide may be considered. Heart failure with congestion can be managed with careful administration of high-dose loop diuretics, supported by thiazides and acetazolamide when necessary. Clinical trials are underway to further evaluate this strategy.

Phenotype and outcome correlates of high dose loop diuretics in type 1 pulmonary hypertension

Abstract Background Use of higher dose of loop diuretics has been associated with worse survival in acute and chronic heart failure. The use of loop diuretics in type 1 pulmonary hypertension (PAH) is generally less frequent compared to heart failure and required doses may be lower. the clinical and prognostic characteristics of patients requiring high dose of loop diuretics in PAH remain unexplored. Purpose We studied the characteristics of patients requiring different doses of loop diuretic and their association with survival in PAH. Methods Patients with a diagnosis of PAH according to 2015 European guidelines criteria enrolled from 2001 and 2021 at seven European centers for the management of PAH and with available information on loop diuretic use were retrospectively included in the study. High dose diuretic use was defined according to the median dose of furosemide in the overall cohort and patients were then divided into two subgroups: no/low dose and high dose diuretic use. Primary outcome was 5-year survival. Predictors of high dose diuretic use were assessed by multivariable logistic regression analysis. Multivariable Cox regression analysis was performed to test the association between high dose diuretic use and 5-year survival. Results Among the 402 patients included (median age 61 years, IQR 49-74; 67% females), 231 (57%) were treated with loop diuretics. Median furosemide dose was 25 mg (IQR 0-40 mg) and accordingly patients were divided in no/low dose (n. 260, 65%, median dose 0 mg, IQR 0-20) vs high dose (n. 142, 35%, median dose 40, 50-100) diuretic ones. Patients in the high dose group were older, had more comorbidities, including impaired renal function (Figure 1) and the characteristics of a more severe disease (41% vs 27% at intermediate-high risk and 42% vs 22% at high risk based on COMPERA 2.0 classification, p&amp;lt;0.001). Predictors of high dose loop diuretic use were obesity (OR 2.04, 95%CI 1.06-3.91, p=0.032), COMPERA 2.0 risk class (OR 1.66, 95%CI 1.19-2.31, p=0.003) and right atrial pressure risk class (OR 2.23, 95%CI 1.42-3.51, p=0.001). Rates of monotherapy, dual and triple combination therapy were similar in patients at no/low vs high dose. Crude 5-year survival was significantly lower in patients in the high dose group (log-rank p=0.002). However, after adjustment for age, sex and main risk factors (i.e. COMPERA 2.0 score, TAPSE/PASP, right atrial pressure and cardiac index), high loop diuretic dose was not significantly associated with higher 5-year mortality risk. Conclusions Use of high dose of loop diuretics in PAH characterizes patients with higher burden of comorbidities, more severe disease and worse survival. However, in PAH the need of high loop diuretic dose represents a marker of disease severity rather than an independent prognostic factor.Figure 1Figure 2.

Diuretic use and outcomes in patients with HFrEF: Insights from the VICTORIA trial

Abstract Background In the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial, vericiguat, compared with placebo, reduced the risk of cardiovascular death (CVD) and heart failure hospitalization (HFH) in patients enrolled shortly after a worsening heart failure (WHF) event. We examined the clinical outcomes and efficacy of vericiguat as it relates to the background use of loop diuretics in this population of patients with WHF. Methods We calculated the total daily loop diuretic dose equivalent to furosemide dosing at randomization and categorized these as &amp;lt;40, 40, and &amp;gt;40 mg total daily dose (TDD). The primary composite outcome of CVD or HFH and its components were evaluated as clinical outcomes and expressed as adjusted hazard ratios (adjHR) and 95% confidence intervals (95% CI). Post-randomization rates of change in TDD and safety were also examined. Results Of 4434 patients with diuretic dose information available at randomization, 647 (14.6%) were on &amp;lt;40 mg, 1633 (36.8%) were on 40 mg, and 2154 (48.6%) were on &amp;gt;40 mg TDD. Patient characteristics revealed those patients taking &amp;gt;40 mg TDD were more often in NYHA Class III/IV, diabetic, and had higher NT-proBNP, lower eGFR, less triple guideline-based HF therapy, and a higher MAGGIC risk score. The composite event rate of CVD or HFH per 100 patient years (pt-yrs) progressively increased with higher doses of diuretics: 29.8 per 100 pt-yrs for 40 mg TDD: adjHR 1.23 (95%CI 1.02-1.49); 48.1 per 100 pt-yrs for &amp;gt;40 mg TDD adjHR 1.50 (95%CI 1.25-1.81), relative to &amp;lt;40 mg TDD (22.5 per 100 pt-yrs). Results were similarly observed for the components of the composite endpoint (Figure). There was no significant interaction for the efficacy of vericiguat vs placebo for any outcome examined according to TDD at randomization (p-interaction &amp;gt;0.72, 0.57 and 0.64 for the primary endpoint, CVD and HFH). Diuretic dose changes post-randomization were assessed in 3684 eligible patients (followed for a median duration of 14.2 months). By treatment group, there were similar rates of up-titration (26.7 and 29.4 per 100 pt-yrs), down-titration (13.8 and 15.4 per 100 pt-yrs), and stopping of diuretic use (23.4 and 24.2 per 100 pt-yrs) observed for vericiguat and placebo groups, respectively. Conclusions The amount of loop diuretic TDD at randomization was associated with a higher risk phenotype commensurate with worse outcomes. However, the efficacy of vericiguat was preserved across this range of different loop diuretic doses used by patients with recent WHF in VICTORIA.

Use of loop diuretics in patients with chronic heart failure: an observational overview

IntroductionThis study aimed to evaluate the use and dose of loop diuretics (LDs) across the entire ejection fraction (EF) spectrum in a large, ‘real-world’ cohort of chronic heart failure (HF)...

Chylous ascites associated with primary pulmonary hypertension: A case report and literature review

Chylous ascites is a rare condition that results from the accumulation of lymph in the abdominal cavity through a variety of mechanisms. We hereby report a case of chylous ascites in a 67-year-old woman who was admitted to our hospital with abdominal distension, bilateral lower extremity edema, and shortness of breath on exertion. The patient had a long history of primary pulmonary hypertension, cor pulmonale, and diabetes mellitus. Imaging studies revealed massive peritoneal fluid, which, after drainage, was found to be consistent with chylous ascites. The patient received high doses of diuretics with a marked improvement in symptoms over the following days. There was no reaccumulation of ascites by the time of discharge. To the best of our knowledge, there are few cases in the literature where chylous ascites has been reported in association with primary pulmonary hypertension.

Sodium-glucose cotransporter-2 inhibition in a CKD patient with severe heart failure treated by high-dose diuretics and peritoneal ultrafiltration: lesson for the clinicalnephrologist.

Sodium-glucose cotransporter-2 inhibition in a CKD patient with severe heart failure treated by high-dose diuretics and peritoneal ultrafiltration: lesson for the clinicalnephrologist.

Diuretic dose is a strong prognostic factor in ambulatory patients awaiting heart transplantation.

The prognostic value of 'high dose' loop diuretics in advanced heart failure outpatients is unclear. We aimed to assess the prognosis associated with loop diuretic dose in ambulatory patients awaiting heart transplantation (HT). All ambulatory patients (n=700, median age 55years and 70% men) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 were included. Patients were divided into 'low dose', 'intermediate dose', and 'high dose' loop diuretics corresponding to furosemide equivalent doses of ≤40, 40-250, and >250mg, respectively. The primary outcome was a combined criterion of waitlist death and urgent HT. N-terminal pro-B-type natriuretic peptide, creatinine levels, pulmonary capillary wedge pressure, and pulmonary pressures gradually increased with higher diuretic dose. At 12months, the risk of waitlist death/urgent HT was 7.4%, 19.2%, and 25.6% (P=0.001) for 'low dose', 'intermediate dose', and 'high dose' patients, respectively. When adjusting for confounders, including natriuretic peptides, hepatic, and renal function, the 'high dose' group was associated with increased waitlist mortality or urgent HT [adjusted hazard ratio (HR) 2.23, 1.33 to 3.73; P=0.002] and a six-fold higher risk of waitlist death (adjusted HR 6.18, 2.16 to 17.72; P<0.001) when compared with the 'low dose' group. 'Intermediate doses' were not significantly associated with these two outcomes in adjusted models (P>0.05). A 'high dose' of loop diuretics is strongly associated with residual congestion and is a predictor of outcome in patients awaiting HT despite adjustment for classical cardiorenal risk factors. This routine variable may be helpful for risk stratification of pre-HT patients.

AA Amyloidosis Secondary to Horton's Disease Complicated by Pulmonary Fibrosis: A Very Challenging Diagnosis and Therapy

AA amyloidosis is a classic and serious complication of many chronic inflammatory processes, whether of infectious, autoimmune, or neoplastic origin. It is frequently complicated by kidney damage, often in the form of a nephrotic syndrome. Giant cell arteritis is a common inflammatory arteritis in the elderly; however, it rarely causes AA amyloidosis. We report a rare case of Horton disease causing AA amyloidosis in an elderly patient with history of myopericarditis and repeated episodes of congestive heart failure. Patient was treated initially with dual therapy based on corticosteroids and anti TNF therapy (Tocilizumab) associated with heart failure therapy recommended by the European society of cardiology (ESC 2021 guidelines on Heart Failure). The initial outcome was favorable but later complicated by the involvement of the lungs; pulmonary fibrosis, responsible for repeated episodes of pleural effusion non controlled in spite of high dose of loop diuretics and repeated pleural punction. Patient died shortly after her second hospitalization due to respiratory insufficiency.

Safety and Efficacy of Empagliflozin and Diuretic Use in Patients with Heart Failure and Preserved Ejection Fraction

The diuretic effect of sodium-glucose cotransporter 2 inhibitors may result in interaction with background diuretic therapy in patients with heart failure and preserved ejection fraction (HFpEF). To assess the safety and efficacy of empagliflozin in combination with background diuretic therapy and the association of empagliflozin with the need for conventional diuretics. This was a post hoc analysis of the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved). EMPEROR-Preserved was a phase 3, randomized, placebo-controlled, double-blind clinical trial conducted from March 2017 to April 2021. Patients with class II to IV heart failure and left ventricular ejection fraction greater than 40% were included. Of 5988 patients enrolled, 5815 (97.1%) had baseline data on diuretic use and were included in this analysis, which was conducted from November 2021 to August 2022. Participants in EMPEROR-Preserved were randomized to empagliflozin or placebo. In this analysis, participants were divided into 4 subgroups: no diuretics and furosemide-equivalent diuretic dose of less than 40 mg, 40 mg, and greater than 40 mg at baseline. The main outcomes of interest were first hospitalization for heart failure (HHF) or cardiovascular death (CV death) and its components. Association of empagliflozin vs placebo with outcomes by baseline diuretic status (no diuretic vs any dose) and dose (no diuretic, <40 mg, 40 mg, and > 40mg) was assessed. Association of empagliflozin use with changes in diuretic therapy was also studied. Among 5815 patients (mean [SD] age, 71.9 [9.4] years; 2594 [44.6%] female) with known baseline diuretic use, 1179 (20.3%) were not taking diuretics, 1725 (29.7%) were taking less than 40 mg, 1772 (30.5%) were taking 40 mg, and 1139 (19.6%) were taking greater than 40 mg. In the placebo arm, patients with higher diuretic doses had worse outcomes. Empagliflozin decreased the risk of HHF or CV death, regardless of background diuretic status (hazard ratio [HR], 0.81; 95% CI, 0.70-0.93] for the diuretic group vs HR, 0.72; 95% CI, 0.48-1.06 for the nondiuretic group; P for interaction = .58). Similarly, diuretic status was not associated with changes in improvements in first HHF, total HHF, rate of decline in estimated glomerular filtration rate, and Kansas City Cardiomyopathy Questionnaire 23 clinical summary score with empagliflozin. Findings were consistent when patients were categorized by diuretic dose. Empagliflozin was associated with a decreased likelihood of diuretic dose escalation (HR, 0.74; 95% CI, 0.65-0.84) and an increased likelihood of de-escalation (HR, 1.15; 95% CI, 1.02-1.30). Empagliflozin was associated with an increased risk of volume depletion in patients taking diuretics (HR, 1.34; 95% CI, 1.13-1.59). In this study, treatment with empagliflozin was similar regardless of diuretic use or dose. Empagliflozin use was associated with decreased conventional diuretic dosing. ClinicalTrials.gov Identifier: NCT03057951.

P177 COR TRIATRIATUM DEXTER: THE ROLE OF TRANSTHORACIC ECHOCARDIOGRAPHY

Abstract Introduction Cor triatriatum dexter (CTD) is an extremely rare congenital cardiac abnormality and its prompt recognition by transthoracic echocardiography (TTE) is essential for a correct diagnosis. Case presentation An 82–years–old woman was admitted to our cardiologic ward for worsening dyspnoea. The physical examination revealed a bilateral lower extremity oedema with elevated jugular venous pressure and hepatomegaly. The ECG showed atrial fibrillation with a heart rate of 70 bpm already treated with beta–blockers and direct–acting oral anticoagulant. TTE revealed a left ventricle with normal dimensions and function, a dilated right ventricle with a mild systolic dysfunction and increased wall thickness, a marked dilation of the right atrium and a tricuspid severe regurgitation. A deeper analysis of the right atrium revealed the presence of membrane partitioning the chamber into two compartments (Figure 1). The separation was incomplete as demonstrated by the flow across the membrane with Color–Doppler technique (Figure 2). The patient was treated using high doses of diuretics with a subsequent clinical improvement. A percutaneous intervention on the tricuspid valve was planned by the Heart Time. Discussion CTD derives from the persistence of the right valve of the sinus venosus resulting in a complete or incomplete fibromuscular band which separates the right atrium into two cavities. The spectrum of clinical manifestations is broad, based upon the degree of separation. In older patients CTD is often asymptomatic and incidentally found during diagnostic imaging examinations. TTE plays a key role in the identification of CTD, as a first–line diagnostic imaging tool. It, also, allows a differential diagnosis with a prominent eustachian valve, chiari network, and thebesian valve. However, in difficult cases a multiparametric approach is required including transoesophageal echocardiogram or cardiac magnetic resonance. Echocardiography has a pivotal role in the prompt recognition of other cardiac abnormalities associated with CTD such as atrial septal defect or patent foramen ovale, right ventricular hypoplasia and Ebstein’s anomaly. In our case, none of these were documented. Atrial fibrillation should be investigated due to severe atrial chamber dilation. A multiplane evaluation of the right atrium and the Color–Doppler technique are helpful to visualize the configuration of the membrane and evaluate the absence of flow disturbances.

P220 PERIPARTUM CARDIOMYOPATHY: HOW TO RECOGNIZE AND TREAT IT

Abstract Introduction Peripartum cardiomyopathy is characterized by LV systolic dysfunction in the absence of other existing cardiac disease. It presents with clinical signs of acute heart failure, with ventricular arrhythmias or cardiac arrest in the last stages of pregnancy up to 5–6 months after delivery. The LV may be non–dilated, but EF is usually &amp;lt;45%. Initial EF &amp;lt;30%, end–diastolic LV diameter ≥6 cm, and RV involvement are associated with adverse outcomes. Case report: 44–year–old female, denies CAD and home therapy. It occurs due to the appearance of peripheral edema, worsening dyspnea and forced orthopneic decubitus arising after cesarean delivery which occurred 3 days earlier. On auscultation: MV abolished at the right base with diffuse rales. In the laboratory increased BNP is evident. (1485 pg/mL). On ECG Sinus tachycardia, 126 bpm. New onset BBSs. PA 100/60. Respiratory acidosis at the EGA. On Echocardiogram (Fig.1) dilated LV with severe reduction of EF 25/30%, moderate–severe IM, RV within limits. Moderate IT with PAPs 40 mmHg. Vena cava dilated, hypo collapsible. Minimal pericardial detachment. At Wcm Pulmonary CT with picture of acute pulmonary edema and apical–basal right pleural effusion, cardiogenic involvement in the interstitial–alveolar phase (Fig. 2). It is treated with inotropics, high dose diuretics and CPAP ventilation with progressive improvement. She underwent Cardiac MR (Fig. 3), to exclude ischemia, myocarditis or heart disease, which described a picture of non–ischaemic dilated heart disease of the LV with severe systolic dysfunction, moderate RV dysfunction and modest MI. On discharge, therapy with B–blockers, loop diuretics, MRA, ARNI and subsequently SGLUT–2 inhibitor was introduced. In relation to age and EF she was referred for evaluation for transplant listing and CRT–D evaluation. Conclusion it is a rare disease: 50% of patients improve with standard medical treatment; 25% develop chronic heart failure and the rest die in the course of the disease. The onset is subtle with non–specific signs and symptoms often confused with "inconveniences" related to the pregnancy itself. To limit the diagnostic delay it is necessary to pay attention to the appearance of tachycardia, third heart sound, basal crackling rales and jugular venous turgor, since they are not physiologically present in pregnancy and to carry out a control echocardiogram especially if in old age.

Therapeutic approach in heart failure with poor diuretic response: peripheral ultrafiltration vs. conventional treatment.

Patients with heart failure (HF) admitted for decompensation often require high doses of intravenous diuretics. This study aims to analyse whether the use of peripheral ultrafiltration (UF) in patients hospitalized for acute HF with systemic-predominant congestion results in better hydric control, renal protection, and reduction of hospital stay compared with conventional treatment. This study was a retrospective, comparative, single-centre study of 56 patients admitted for HF with systemic congestion with a poor diuretic response after diuretic escalation. One group underwent peripheral UF (35 patients) and others were maintained on intense diuretic treatment (control group, 21 patients). The diuretic response and days of hospital stay were compared between and within groups. The baseline characteristics of both groups were similar: males with right ventricular failure and renal dysfunction. The inter-group analysis showed that patients who received UF had better glomerular filtration rate (GFR; UF: 39.2±18.2 vs. control: 28.7±13.4mL/min; P=0.031) and higher diuresis (UF: 2184±735 vs. control: 1335±297mL; P=0.0001) at hospital discharge despite less need for diuretic drugs. Days of hospital stay were shorter in the UF group (UF: 11.7±10.1 vs. control: 19.1±14.4days; P=0.027). Intra-group analysis showed that patients receiving UF improved GFR, increased diuresis, and reduced weight at discharge (P<0.001), whereas patients on conventional treatment only experienced improved weight but worsening renal function at discharge. In patients with acute HF with systemic congestion and diuretic resistance, UF compared with conventional treatment produces greater decongestion and renal protection, reduces the total diuretic load, and shortens the length of hospital stay.