Diuretic Dose Research Articles

Diuretic dosing and outcomes with torsemide and furosemide following hospitalization for heart failure: the TRANSFORM-HF trial

Abstract Background The TRANSFORM-HF trial found no significant difference in all-cause mortality and all-cause hospitalization following hospitalization for heart failure (HF) with a diuretic strategy of torsemide versus furosemide. However, the impact of diuretic dosing on the trial results and whether the relationship between dosing and outcomes differs between torsemide and furosemide is unclear. Purpose To assess and compare the associations between diuretic dosing and outcomes with torsemide and furosemide. Methods TRANSFORM-HF was an open-label, pragmatic trial that randomized 2859 patients hospitalized for HF in the United States to a diuretic strategy of torsemide versus furosemide after discharge. These post-hoc analyses categorized patients according to investigator-selected discharge dose tertile of torsemide and furosemide, i.e. tertile 1) ≤40 mg, 2) >40-80 mg and 3) >80 mg of furosemide equivalents using a 2:1 conversion with torsemide. Study endpoints were all-cause mortality, all-cause hospitalization, composite all-cause mortality or hospitalization, and change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). Results Dosing data were available for 2379 (83%) of patients with median age 65 years (IQR: 56, 75), 883 (37.1%) were women, and 812 (34.2%) were Black. When categorized by discharge dose, a total of 1136 (47.8%) patients were included in dose tertile 1, 696 (29.2%) in tertile 2 and 547 (23.0%) in tertile 3. For all-cause mortality, furosemide showed adjusted hazard ratios (aHR) of 1.21 (95% CI: 0.91, 1.59) for tertile 2 and 1.40 (95% CI: 1.04, 1.88) for tertile 3 compared with tertile 1. For torsemide aHR for all-cause mortality were 1.74 (95% CI: 1.32, 2.30) for tertile 2 and 1.58 (95% CI: 1.14, 2.19) for tertile 3 compared with tertile 1 (Table 1). The risk of adverse events increased similarly with dose for both diuretics and no statistically significant interaction between loop diuretic and dose was observed (Pinteraction=0.17). Likewise, for the endpoints of all-cause hospitalization and the composite of all-cause mortality and hospitalization, higher doses of furosemide and torsemide aligned with higher risk of both endpoints, and interaction p-values that did not demonstrate statistical significance by loop diuretic (all-cause hospitalization: Pinteraction= 0.28, all-cause mortality and hospitalization: Pinteraction=0.38) (Table 1). Changes in KCCQ-CSS were similar across the range of dose tertiles from baseline to month 12 for both furosemide and torsemide (Table 2). Conclusions Following hospitalization for HF, no clinical differences were observed across the dosing spectrum in all-cause mortality, all-cause hospitalization, or KCCQ-CSS at 12-mornths between torsemide and furosemide. Irrespective of diuretic agent used, increasing dose of loop diuretics correlates with worse clinical outcomes.

Effect of sodium-glucose cotransporter-2 inhibitor (SGLT2-i) in patients with LVAD: a systematic review and meta-analysis

Abstract Introduction Sodium-glucose cotransporter-2 inhibitor (SGLT2-i) have been shown to reduce risks of clinical events in patients with heart failure (HF). However, data on the use of SGLT2-i in patients with left ventricular assist devices (LVAD) are scarce. We thought to assess the efficacy and safety of SGLT2-i in patients with LVAD Methods A systematic search was done in PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to December 2023. We used all relevant words for "SGLT2-i" and "LVAD" to search in databases and we included studies and published abstracts in peer-reviewed journals of studies assessed SGLT2-i in patients with LVAD. The efficacy and safety data were extracted across the studies. RevMan 5.4.1 was used for meta-analysis. Results Three studies and eight abstracts totaling 209 patients using SGLT2-i were included. Empagliflozin, Dapagliflozin, and Canagliflozin were the used SGLT2-i across the included studies. SGLT2-i effectively decreased hemoglobin A1c (HbA1c) (Mean = -0.44, 95% CI [-0.79, -0.09], p = 0.01) and diuretic dose (Mean=-2.54, 95% CI [-3.56, 1.51], p< 0.00001) from baseline. No significant improvement was found for glomerular filtration rate (GFR), B-type natriuretic peptide (BNP), or mean pulmonary artery pressure (MPAP). Regarding safety, the pooled percentage of people with driveline infection was 9.33%, 95% CI [2.05, 16.60], p=0.01. Conclusion SGLT2-i effectively improves HbA1c and diuretic dose in patients using LVAD. Further randomized studies with a large number of participants may be warranted.

Accuracy of right atrial pressure estimation by transthoracic echocardiography

Abstract Background/Introduction Transthoracic echocardiography provides an estimate of right atrial pressure (RAP) using the guideline-recommend method of measuring inferior vena cava (IVC) diameter and collapsibility. Despite being ubiquitously reported and necessary for the estimation pulmonary artery systolic pressure, the accuracy of this method for RAP estimation has not been rigorously validated. Purpose To evaluate the accuracy of the guideline-recommended method for the estimation of RAP by TTE. Methods A single center, retrospective chart review of patients who had a TTE and right heart catheterization (RHC) within 48 hours of each other from January 2018 to December 2020. Maximum and minimum IVC diameter were measured by trained study personnel. Accuracy was then stratified by the presence/absence of a history of two variables that could modify IVC diameter independent of RAP—syncope, which is associated with more dilated IVC in some studies and liver disease, which could result in compression (from parenchymal fibrosis surrounding the IVC) or dilation (from diversion of portal blood flow through the IVC among other mechanisms) of the IVC. Results The 117 patients who met inclusion criteria had a median age of 67 years old (interquartile range [IQR] 58 – 75) and median RAP of 13 mmHg (IQR 8 – 18) on RHC. The median time between TTE and RHC was 9.6 hours (IQR 3.8 – 24.5 hours) during which 24 (20.5%) patients received intravenous fluids (median 220 mL administered; IQR 145 – 320). Forty-three (35.9%) received diuretics between the studies with most patients receiving either 1 (26 patients, 61.9% of those who received diuretics) or 2 (13 patients, 31.0%) diuretic doses. In evaluating accuracy, only 26 patient’s (20.5%) RAP by RHC fell within estimated RAP range by TTE (Figure 1). After excluding the 60 patients who received fluids and/or diuretics between the TTE and RHC, the TTE estimate was still only accurate in 13 (22.8%) patients. When analyzing how each subcomponent of the TTE guidelines for RAP estimation correlated with RAP via RHC, maximum IVC diameter and percent collapsibility had Pearson’s correlation coefficients of 0.47 and 0.24 respectfully (Figure 2A and 2B). Past medical history was significant for syncope in 16 patients (13.7%) and liver disease in 8 patients (6.8%). Compared to those without each factor, the absolute accuracy of the TTE estimate was lower when stratified by a history of syncope (12.5% accurate vs 21.8%, p = 0.60) and liver disease (12.5% vs 21.2%, p = 0.90) though neither were statistically significant. Conclusion In this retrospective chart review, RAP estimation by TTE using the guideline-recommended method had limited accuracy. Prospective evaluation with minimal time between RHC and TTE is needed to validate the accuracy of the TTE guidelines.Accuracy of TTE for RAP estimationCorrelation between RAP & TTE Variables

Mechanisms affecting the neutrophil to lymphocyte ratio in heart failure: a prospective CMR study

Abstract Background The neutrophil-to-lymphocyte ratio (NLR) is a simple measure of inflammation defined as the ratio of the neutrophils to lymphocytes as measured in the full blood count. It is well known that patients with heart failure (HF) have elevated levels of pro-inflammatory cytokines. It has been demonstrated in a recent meta-analysis that elevated NLR in heart failure is significantly associated with worse outcomes including all-cause mortality, heart failure readmissions and cardiovascular death. Purpose Given this association between NLR and adverse prognosis in HF, we aim to identify which factors are associated with an elevated NLR. This may help to recognise patients at higher risk and guide management. Methods Patients with newly diagnosed HF and left ventricular ejection fraction <50% on referral echocardiogram were prospectively recruited at the time of referral for cardiovascular magnetic resonance (CMR). Exclusion criteria included prior revascularisation, myocardial infarction, anginal chest pain, congenital heart disease and suspected myocarditis. In one appointment patients (N=599) underwent clinical assessment, medication review, full blood count and CMR. The CMR protocol included quantitative assessment myocardial blood flow at stress and rest, assessment of ischaemic and non-ischaemic fibrosis by late gadolinium enhancement imaging and T1 and T2 mapping. Guideline directed medical therapy was determined by the referring physician. Baseline demographic data, medication and MRI results were recorded for all patients. NLR was calculated from full blood count and split into tertiles. Clinical and CMR parameters were compared between tertiles by analysis of variance and chi squared test. Results See Table 1 The factors which were found to be significantly associated with an elevated NLR were age, atrial fibrillation, NTproBNP, diuretic dose, inducible ischaemia and ischaemic fibrosis. Of note there was no significant difference between groups in terms of guideline directed medical therapy use or other CMR parameters. Conclusion NLR is increasingly recognised as a marker of adverse risk in patients with heart failure. This prospective study of 599 heart failure patients with reduced ejection fraction has identified that an elevated NLR is associated with: 1. Evidence of congestion as evidenced by NTproBNP results and increased diuretic doses. 2. Occult coronary artery disease as shown by greater levels of inducible ischaemia and ischaemic fibrosis. These findings suggest that the adverse prognosis associated with elevated NLR in heart failure may be mediated by worsening congestion and occult coronary artery disease. Importantly there was no association between myocardial inflammation or oedema (measured as native T1 and T2) and NLR. Whether NLR improves with medical therapy of heart failure remains to be established and our findings need to be validated in more varied cohorts of patients with heart failure.

Randomized trial assessing worsening renal function with dapagliflozin addition in acute decompensated heart failure: ROAD-ADHF trial

Abstract Background Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 inhibitor, has shown to reduce cardiovascular mortality in patients with chronic heart failure.1) In addition, DAPA can enhance diuresis in patients with acute decompensated heart failure (ADHF).2) However, there is little known how early initiation of DAPA might impact the worsening renal function (WRF) when combined with standard decongestive therapy for ADHF. Purpose We aimed to evaluate the impact of initiating DAPA within 24 hours after ADHF admission on WRF, compared to standard decongestive therapy with loop diuretics alone. Methods We enrolled consecutive ADHF patients with a left ventricular ejection fraction (LVEF) less than 50%. The patients were prospectively randomized to either the DAPA group who received DAPA at a dose of 10 mg once daily within 24 hours of admission or the conventional therapy group (CON group) who received loop diuretics alone. Furosemide, loop diuretic, dosage was adjusted by increase or decrease of 10 mg to maintain urine output between a 1-2 mL/kg/hour.3) The primary endpoint was the incidence of WRF, which was defined as an increase in the serum creatinine of ≥ 0.3 mg/dL from baseline within 7 days of admission.4) Additionally, right heart catheterization (RHC) was performed before discharge if the consent was obtained. Results From May 2021 to May 2023, we analyzed a total of 114 patients (56 in the DAPA group and 58 in the CON group). The mean age was 73 years, 35% were female, and the mean LVEF was 32.5%. There was no significant difference in the incidence of WRF between two groups (16.1% in the DAPA group vs. 12.1% in the CON group, P=0.54, Figure 1). The cumulative loop diuretics dose over 7 days was lower in the DAPA group than CON group (184 ± 9.64 mg vs. 214 ± 9.81 mg, P=0.03, Figure 2). RHC before discharge was performed in 54 patients (96.4%) in the DAPA group and in 54 (93.1%) in the CON group. There were no significant differences in the pulmonary artery wedge pressure, pulmonary artery pressure, right atrial pressure, and cardiac index by the thermodilution method or the Fick method between two groups. Conclusion This randomized prospective trial revealed the early initiation of DAPA within 24 hours of admission for ADHF reduced loop diuretic demand without inducing WRF compared to standard decongestive therapy.Figure 1Figure 2

Liver function tests in patients receiving high-intensity care after hospital admission for acute heart failure: the STRONG-HF trial

Abstract Background/Introduction Episodes of acute heart failure (AHF) unfavorably affect extra-cardiac organs such as the liver due to altered hemodynamics and neurohormonal activation. In AHF, elevated levels of levels of alanine aminotransferase (ALT) and total bilirubin (tBil) may reflect congestion and impaired liver function, while lower levels of ALT (which is also produced in muscle cells) correlate with malnutrition and sarcopenia. Thus, the clinical importance of these markers in AHF and the post-discharge period is unclear. Purpose To assess circulating concentrations of ALT and tBil in patients with AHF before discharge and during high-intensity care (HIC) vs usual care follow-up in association with clinical outcomes. Methods ALT and tBil concentrations were measured 1-2 days before discharge in patients hospitalized for AHF (baseline), and again after 90 days of either HIC or usual care according to the STRONG-HF protocol. Baseline values and changes in ALT and tBil were analyzed in association with the primary outcome of all-cause death or HF readmission by day 180. Results At baseline, the median (Q1-Q3) concentrations of ALT and tBil were 21 (15-32) U/L and 14 (10-21) umol/L, respectively. Lower levels of both ALT and tBil were associated with female sex, Black race, lower BMI, higher LVEF, lower hemoglobin, lower creatinine and less frequent atrial fibrillation/flutter, while there were no significant associations with age. Patients with lower ALT, but not tBil, were more likely to have edema, elevated JVP and orthopnea, and used higher loop diuretic doses and less beta-blockers, pre-randomization (Figure, panel A). ALT was inversely associated with risk for the primary outcome (HR 0.81 [95%CI 0.65,1.00) per log increment, p=0.05), while there was no association with risk for tBil (HR 1.04 [95%Ci 0.84-1.28], p=0.73) (Figure, panel B). After 90 days, ALT and tBil concentrations were lower than at baseline, with a greater reduction in tBil in the HIC group vs usual care group (mean -1.7 [95%CI -3.0,-0.4] umol/L, p=0.01), while there was no significant between-group differences in ALT changes (mean -0.6 [95%CI -4.7,3.4] U/L, p=0.75) (Figure, panel C). The treatment effect of HIC over usual care on the primary outcome was consistent across the range of baseline ALT (P-interaction=0.30) and tBil (P-interaction=0.80) (Figure, panel D). Conclusion Contrary to our hypothesis of higher liver function tests with hepatic congestion in AHF, lower ALT was associated with more congestion and worse outcomes among patients hospitalized for AHF in STRONG-HF. There was no prognostic value from tBil levels. This suggests that ALT may be a marker of sarcopenia in these patients. Importantly, the beneficial effect of HIC on clinical outcomes is consistent irrespective of ALT and tBil levels at discharge.Figure

Glutathione s-transferase pi is a marker of loop diuretic resistance in patients with congestive heart failure exacerbation

Abstract Background Loop diuretic resistance (LDR) in patients with heart failure (HF) exacerbation is associated with worse clinical outcomes, greater symptom burden and mortality. Diagnosis and treatment of LDR remains a significant clinical dilemma. Purpose To assess the ability of different urine biomarkers to predict LDR in patients with HF exacerbation. Methods Consecutive patients with congestive HF exacerbation were prospectively included in the study. HF was diagnosed according to ESC 2021 HF Guidelines definition. Congestion was defined as a presence of one or more of the following signs: edema, ascites, pleural effusion. LDR was defined as persistent congestion on the 4th day of hospital stay despite high i.v. loop diuretic dose. Urine biomarkers released from different parts of the nephron (Kidney Injury Molecule-1 - KIM-1, N-acetyl-β-D-glucosaminidase - NAG, uromodulin, glutathione S-transferase Pi - pi-GST, aquaporin-2), transthoracic echo, clinical and biochemical parameters were evaluated on the 1st and 4th day of hospital stay. 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, median left ventricle ejection fraction (EF) 35.3 (26,5; 49) %, 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: urine pi-GST concentration on admission and on the 4th day, right ventricle to pulmonary circulation coupling index (TAPSE/PASP ratio), presence of mitral regurgitation, serum creatine concentration, serum urea concentration, serum LDL concentration. Logistic regression analysis identified pi-GST concentration as a significant independent risk factor for LDR in this population: odds ratio (OR) 5.75 [95% confidence interval (CI) 1.271–25.990]. Conclusions Urine pi-GST on admission and after 4 days of treatment might be a marker for a development of LDR in patients with congestive HF exacerbation.

Automatic telephonic follow up in heart failure by a natural language processing artificial intelligence: pilot program

Abstract Introduction Heart failure (HF) burden on public health is substantial and efficient patient management strategies are needed. Traditional methods of HF monitoring face limitations in scalability and effectiveness. Artificial Intelligence (AI) might offer novel solutions for enhanced resource management and alleviation of healthcare burdens. Purpose To study the feasibility of implementing automatic remote monitoring via phone calls operated by AI in a HF unit. Methods We conducted a non-randomized, open, pilot trial employing an AI technology based on natural language processing for autonomous telephone outreach for the follow up of HF patients. 86 patients from a tertiary hospital HF unit undergoing pharmacological titration and education were enrolled. The AI conducted weekly calls to gather symptomatology, vital signs, and health status changes, which were then displayed on a virtual platform featuring alerts preconfigured by the research team. These alerts guided patient communication and intervention as deemed necessary by a specialized nurse. Results Characteristics of patients are shown in Table 1. The AI followed these patients for a median of 251.5 days. 2773 telephonic calls were performed. We estimate an equivalent to 1445h of work (17.2 days/month). Adherence was high during the study, with 98% of the calls completed. 1427 alerts were generated, being the most frequent weight change (251; 17.6%), orthopnea (220; 15.4%) and fatigue (187; 13.1%). It led to 487 remote interventions, most of them consisting in calling the patient for assessment (409; 84.0%), but also in adjusting medication remotely (34; 7.0%). See Figure 2. A HF telemedicine specialized nurse required 205min per week for alert review, 2.38min/patient-week. 2 patients died, one from cardiovascular causes, and 7 patients had a HF hospitalization, 42.9% with previous alarms. 20 events of worsening HF were recorded, comprising hospitalization, emergency visit or IV diuretic administration. Oral diuretic dose was increased in 22 occasions, 15 of them remotely in response to an alert raised by the AI operator. At 6 months functional class globally improved (p = 0.028), but NTproBNP increased (p=0.0472). Quality of life was evaluated at baseline and at 6 months, with no change in EQ5D5L (median 0.717, change -0.005, p 0.71) or PHQ4 (median 2.88, change -0.29, p 0.7792), but KCCQ12 total score worsened (median 74.49, change -2.32, p 0.048). Experience was rated with 8.97/10 in a satisfaction questionnaire. All patients recommended the program, remarking a closer follow up, better communication and a safety feeling. Conclusions AI enables closer monitoring of patients with HF, maintaining contact with stable patients while also allowing for resource allocation and tracking of higher-risk patients or those experiencing changes in symptoms. A randomized clinical trial comparing to standard follow-up is needed to evaluate this promising technology.Table 1Figure 2

Canagliflozin reduces oral loop diuretic intensification in patients with type 2 diabetes: a participant level pooled analysis of CREDENCE and CANVAS

Abstract Background Patients with type 2 diabetes often have coexistent heart failure or chronic kidney disease (CKD) that require treatment with loop diuretics; however, the prognostic implications of oral loop diuretic intensification are not well characterized. The sodium glucose cotransporter-2 inhibitor canagliflozin reduces the risk of hospitalization for heart failure or cardiovascular death and CKD progression among patients with type 2 diabetes at high cardiovascular risk or with concomitant CKD. Purpose To assess the prognostic implications of oral loop diuretic intensification and the treatment effects of canagliflozin versus placebo on loop diuretic use in high-risk patients with type 2 diabetes. Methods This was a post-hoc participant-level pooled analysis of the CANVAS Program and CREDENCE trial which enrolled patients with type 2 diabetes at high cardiovascular risk or with CKD. Oral loop diuretic intensification was defined as a composite of new loop diuretic initiation (among patients not receiving loop diuretics at baseline) or loop diuretic dose increase (among patients receiving loop diuretics at baseline). We assessed the association between the requirement for loop diuretic intensification and the incidence of subsequent all-cause death. The effect of canagliflozin versus placebo on the composite of loop diuretic intensification as well as its components were evaluated. We further examined the effect of canagliflozin on an expanded post hoc composite of cardiovascular death, hospitalization for heart failure or loop diuretic intensification. Results 2,263 (15.6%) of 14,543 patients were treated with loop diuretics at baseline. Over a median follow-up of 2.2 years, 1,264 patients (9.4%) required oral loop diuretic intensification, of which 981 (77.6%) patients 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 mortality that were 3.5-fold higher (5.9[5.4-6.5] per 100 patient-years) than those not requiring oral loop diuretic intensification (1.7[1.6-1.9] per 100 patient-years). Treatment with canagliflozin reduced the need for oral loop diuretic intensification by 41% (HR 0.59; 95%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); Figure 1. Treatment with canagliflozin similarly reduced an expanded composite of worsening heart failure inclusive of cardiovascular death, heart failure hospitalization or diuretic intensification (HR 0.64; 95%CI: 0.58-0.70). Conclusion Among high-risk patients with T2D, new oral loop diuretic intensification was frequent and associated with an increased risk of subsequent mortality. Treatment with canagliflozin significantly reduced the need for loop diuretic intensification.

Improvement of endorgan function following tricuspid edge-to-edge repair

Abstract Background/Introduction Subjects with severe tricuspid regurgitation (TR) often suffer from impaired endorgan function. The potential to improve endorgan function is an important goal of treatment. Purpose To assess baseline endorgan function and changes in organ function following transcatheter edge-to-edge repair with the TriClip device in subjects with severe TR from the TRILUMINATE Pivotal randomized controlled trial. Methods Right heart catheterization was required prior to enrollment; medication history was collected. Changes in biomarkers, including MELD-XI, GGT, eGFR, BUN, and TR and KCCQ overall summary score were assessed at baseline and 12-month follow-up for all enrolled subjects. A 15% improvement in biomarker levels was considered clinically relevant. The odds of achieving a 15% improvement in biomarkers between baseline and 12-month follow-up was compared between the Device and Control groups (presented as OR [95% CI]). Results A total of 572 subjects were enrolled and randomized. At baseline, subjects had elevated levels of GGT (83.0±87.7 U/L) and MELD-XI score (10.3±5.2), low eGFR (56.7±21.0 mL/min/1.73m2), and elevated BUN (29.5±16.7 mg/dL). Nearly 90% of subjects were on loop diuretics, with approximately 50% taking these in combination with a thiazide or potassium-sparing diuretic. The average diuretic dosage was 71 mg (furosemide equivalent). Most subjects had normal left ventricle ejection fraction (only 5% with LVEF <40%). Subjects had well-managed blood pressure (systolic: 122±13 mmHg, diastolic: 69±10), slightly elevated central venous pressures (12±6 mmHg), systolic pulmonary artery pressures (40±10 mmHg) and pulmonary capillary wedge pressures (15±4 mmHg), and normal transpulmonary gradients (11±4 mmHg). The odds of achieving a 15% improvement in liver and renal function was higher in TriClip patients compared to control: MELD-XI score (1.79 [1.22, 2.63]), GGT (1.83 [1.21, 2.77]), and eGFR (1.81 [1.18, 2.77]) - Fig 1. The favorable changes in organ function observed were also reflected when stratifying subjects by residual TR severity: The odds of a 15% biomarker improvement favored subjects with moderate or less residual TR for MELD-XI score (2.05 [1.39, 3.00]), GGT (1.91 [1.26, 2.90]), and eGFR (1.83 [1.20, 2.80]) compared with subjects who had severe or worse residual TR. Lastly, improvement in these biomarkers also favored subjects with a 15-point or greater improvement in KCCQ compared with subjects with less than a 15-point KCCQ improvement. Conclusions Use of TriClip in subjects with severe tricuspid regurgitation was associated with improvement in kidney and liver function, and this improvement was associated with reduction in the severity of TR. These data provide the first objective evidence of the physiologic impact of TR reduction obtained in a randomized clinical trial.

The Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Implantable Cardioverter Defibrillator (ICD) Shocks in Heart Failure Patients Undergoing Diuretic Therapy.

Implantable cardioverter defibrillators (ICDs) are the standard treatment for patients with reduced left ventricular ejection fraction (LVEF≤35%) to reduce the risk of sudden cardiac death. Loop diuretics can cause electrolyte imbalances leading to an increased incidence of ICD shocks. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown cardiovascular benefits in patients with heart failure (HF), but their effects on ventricular arrhythmias and ICD shocks, particularly in patients receiving different doses of loop diuretics, are not fully understood. This study evaluated the effects of furosemide dose and SGLT2i use on ICD shocks in HF patients with reduced left ventricular ejection fraction (HFrEF). HFrEF patients using oral furosemide and undergoing ICD implantation in our clinic were followed for 12 months to monitor ICD shocks for ventricular arrhythmias. They were grouped according to daily oral furosemide dose and SGLT2i use. Out of 175 patients, the use of high-dose furosemide (>80 mg/day) was significantly higher in the ICD shock group compared to the non-shock group (38.8% vs. 16.7%, p = 0.001), while the use of SGLT2i was lower (19.4% vs. 45.4%, p < 0.001). ICD shocks occurred in 67.6% of patients on high-dose furosemide without SGLT2i and 30.0% with SGLT2i (p < 0.001). Multivariate analysis identified the absence of SGLT2i as an independent predictor of ICD shocks. SGLT2i was associated with reduced ventricular arrhythmias and ICD shocks in HF patients, even when high doses of furosemide were used. The absence of SGLT2i in HF treatment was an independent predictor of ICD shocks.

Diuretic dosing and outcomes with torsemide and furosemide following hospitalization for heart failure: The TRANSFORM-HF trial.

The TRANSFORM-HF trial found no difference in clinical outcomes between torsemide versus furosemide after hospitalization for heart failure. This analysis aimed to assess the impact of diuretic dosing on the primary and secondary clinical outcomes. This post-hoc analysis of TRANSFORM-HF categorized patients into three groups by discharge diuretic dose: (1) ≤40 mg, (2) >40-80 mg, and (3) >80 mg of furosemide equivalents. The associations between discharge dose and 12-month clinical events, and change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), were assessed. Overall, 2379 patients were included, aged 65 years (interquartile range 56-75), 883 (37.1%) women, and 812 (34.2%) Black. Furosemide had adjusted hazard ratios (aHR) for all-cause mortality of 1.21 (95% confidence interval [CI] 0.91-1.59) for discharge dose group 2 and 1.40 (95% CI 1.04-1.88) for group 3, compared with group 1. For torsemide, aHRs were 1.74 (95% CI 1.32-2.30) for group 2 and 1.58 (95% CI 1.14-2.19) for group 3. No evidence of heterogeneity for the association between increased mortality and higher dose was found by loop diuretic type (pinteraction = 0.17). Higher doses of furosemide and torsemide were associated with increased risk of all-cause hospitalization and the composite of all-cause mortality and hospitalization, without evidence of heterogeneity by loop diuretic type (pinteraction > 0.2). Changes in KCCQ-CSS from baseline at 12 months was similar across dose groups for both drugs. Following hospitalization for heart failure, higher loop diuretic dosing was independently associated with worse clinical and patient-reported outcomes. The correlation between higher loop diuretic dose and outcomes was consistent, regardless of loop diuretic used.

Metolazone Versus Chlorothiazide in Acute Heart Failure Patients With Diuretic Resistance and Renal Dysfunction: A Retrospective Cohort Study.

Guidelines recommend intravenous loop diuretics as first-line therapy for patients hospitalized with acute heart failure (AHF) and volume overload. Additional agents can be used for augmentation, but there is limited guidance on agent selection. The study objective was to determine if chlorothiazide or metolazone is associated with differences in diuretic efficacy or safety in loop diuretic-resistant patients with AHF and renal dysfunction (eGFR <45 mL/min/1.73 m²). We conducted a multicenter, retrospective cohort study of patients hospitalized with AHF and renal dysfunction who received metolazone or chlorothiazide in addition to intravenous loop diuretics. The primary end point was a comparison of 24-hour urine output (UOP) between the 24 hours before and after thiazide administration. Secondary and safety end points included weight change, requirement for vasopressors or inotropes, electrolyte abnormalities, and changes in renal function. A total of 221 patients were included. The mean daily diuretic doses were chlorothiazide 632 mg and metolazone 7 mg. The mean 24-hour UOP increased more among chlorothiazide-treated (from 1668 mL to 3826 mL) versus metolazone-treated patients (from 1672 mL to 2834 mL) ( P < 0.001) after the addition of the second diuretic. Statistically significant reductions in serum creatinine were observed in the chlorothiazide group following 72 hours of treatment ( P = 0.016). More hypomagnesemia was observed in the chlorothiazide group; no differences in other electrolytes or changes in weight were observed. Overall, chlorothiazide was associated with a greater increase in 24-hour UOP than metolazone without an excess of potassium or serum creatinine derangements. However, weight changes did not differ significantly between groups. Future prospective studies are needed to confirm potential differences in diuretic response and safety.

TRANSFORM-HF Trial: Choice of loop diuretic in acute heart failure does not matter!

ABSTRACT The major clinical manifestations of heart failure (HF) are due to fluid retention and congestion, and thus, therapy targeting congestion plays a central role in HF management. Furosemide is by far the most commonly prescribed loop diuretic. However, data primarily derived from observational and small randomized trials point toward potential advantages with torsemide use including improvement in functional status, survival, and hospitalization for HF. The TRANSFORM-HF study aimed to answer a pragmatic query faced by physicians managing HF – Does the choice of loop diuretic matter in HF? There was no benefit of torsemide over furosemide in this large study of &gt;2800 patients for mortality, hospitalization, and quality of life. Though, there were a few shortcomings of the study, the results are in sync with current HF guidelines which do not advocate the use of one loop diuretic or other. Hence, the focus in acute HF should be on optimizing the diuretic dose and other guideline-based therapies rather than the type of diuretics. Recent trials of acetazolamide and other diuretics have shown benefits when used in conjunction with loop diuretics. Since the primary care physician is often the first point of medical contact, the manuscript aims to provide insights into their practice. The message is clear that in acute heart failure, there is no benefit of choosing the type of loop diuretic and impetus should be on adding other class diuretics if needed as well as initiating other guideline-directed medical therapies.

Deep-learning generated B-line score mirrors clinical progression of disease for patients with heart failure

BackgroundUltrasound can detect fluid in the alveolar and interstitial spaces of the lung using the presence of artifacts known as B-lines. The aim of this study was to determine whether a deep learning algorithm generated B-line severity score correlated with pulmonary congestion and disease severity based on clinical assessment (as identified by composite congestion score and Rothman index) and to evaluate changes in the score with treatment. Patients suspected of congestive heart failure underwent daily ultrasonography. Eight lung zones (right and left anterior/lateral and superior/inferior) were scanned using a tablet ultrasound system with a phased-array probe. Mixed effects modeling explored the association between average B-line score and the composite congestion score, and average B-line score and Rothman index, respectively. Covariates tested included patient and exam level data (sex, age, presence of selected comorbidities, baseline sodium and hemoglobin, creatinine, vital signs, oxygen delivery amount and delivery method, diuretic dose).ResultsAnalysis included 110 unique subjects (3379 clips). B-line severity score was significantly associated with the composite congestion score, with a coefficient of 0.7 (95% CI 0.1–1.2 p = 0.02), but was not significantly associated with the Rothman index.ConclusionsUse of this technology may allow clinicians with limited ultrasound experience to determine an objective measure of B-line burden.

Characteristics of initiation timing and anticoagulation of continuous renal replacement therapy in patients following cardiac surgery: A retrospective analysis of 28 patients.

Continuous renal replacement therapy (CRRT) used in cardiac surgery-associated acute kidney injury (CSA-AKI) may have different characteristics from other diseases. We reviewed the medical records of patients with CSA-AKI requiring CRRT who underwent cardiac surgery from January 2020 to September 2021. Patients with AKI caused by other reasons who received CRRT during the same period were also evaluated. A total of 28 patients with CSA-AKI and 12 patients with AKI caused by other reasons were enrolled in this study. Compared with AKI patients caused by other reasons, patients with CSA-AKI were found to have lower mean arterial pressure, higher level of bilirubin, higher vasoactive-inotropic score, and larger daily diuretic dosage. The patients with CSA-AKI were prescribed CRRT earlier than the patients with AKI caused by other reasons. There was a significant difference in the CRRT anticoagulation method between patients with CSA-AKI and patients with AKI caused by other reasons. Six patients with CSA-AKI were treated with regional citrate anticoagulation (RCA), and the other 22 patients were treated with low molecular weight heparin or without anticoagulants. The timing of CRRT initiation in patients with CSA-AKI is earlier than that in patients with AKI caused by other reasons. Although RCA is recommended as the preferred anticoagulant for patients without contraindications, patients with CSA-AKI often have circulatory dysfunction and severe liver damage, so the risk of citrate accumulation is greater, whether to use RCA should be determined according to the individual condition of the patient.

Hereditary and wild type transthyretin amyloid cardiomyopathy in Bulgaria in patients suspected for cardiac amyloidosis

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a severe progressive disease, more common than previously expected. The main objectives were to evaluate hereditary and wild type ATTR-CM frequency and clinical manifestations. Material and methods: One hundred seventy-eight patients at mean age 68 &amp;plusmn; 13 years (129 males), referred by cardiologists with suspected cardiac amyloidosis (left ventricular wall thickness &amp;ge; 12 mm and red flags) were evaluated. Pyrophosphate scintigraphy (99mTc-PYP) grade 2-3 myocardial uptake in the absence of monoclonal protein confirmed the diagnosis. Genetic test differentiated variant from wild type ATTR-CM. Endomyocardial biopsy with amyloid typing was performed in two patients. Results: Cardiac amyloidosis was diagnosed in 69 patients: light chain in 24 (13%) and ATTR-CM in 45 patients (25%). Wild type (ATTRwt) was found in 21 (12%) male patients at mean age 81 &amp;plusmn; 6 years and variant type (ATTRv) in 24 patients (13%) at mean age 58 &amp;plusmn; 7 years (15 males). In all ATTRv-CM patients some degree of peripheral polyneuropathy was found. The most common clinical red flags at diagnosis in both ATTRv and ATTRwt were heart failure in all patients, atrial fibrillation (16; 36%), pacemaker (5; 11%), and carpal tunnel syndrome (8; 18%). Severe aortic stenosis (4; 19%), spinal stenosis (2;10%), biceps tendon rupture (1; 5%) were characteristic for the wild type. At follow up, four patients needed a pacemaker for high degree AV block, six patients developed new onset atrial fibrillation, seventeen patients needed either initiation or an increase of the dose of loop diuretic, another 7 patients were hospitalized for heart failure exacerbation. Eight patients (18%) died, 7 (33%) with ATTRwt-CM and 1 (4%) with ATTRv-CM, all with advanced heart failure, 4 with concomitant severe aortic stenosis. Conclusions: This study provides the first nationwide estimates of the frequency and the clinical manifestations of ATTR-CM. Confirming the severity of the disease and poor prognosis, a low threshold for screening is needed for early diagnosis and timely treatment.

Rationale and Design of PURE: A Randomized Controlled Trial to Evaluate Peritoneal Ultrafiltration with PolyCore™ in Refractory Congestive Heart Failure

Introduction: Peritoneal ultrafiltration (PUF) has been proposed as an additional therapeutic option for refractory congestive heart failure (RCHF) patients. Despite promising observational studies and/or case report results, limited clinical trial data exist, and so far, PUF solutions remain only indicated for chronic kidney diseases. In this article, we described a multicenter, randomized, controlled, unblinded, adaptive design clinical trial, about to start, investigating the effects of PolyCore™, an innovative PUF solution, in the treatment of RCHF patients. Methods: The Peritoneal Ultrafiltration in Cardiorenal Syndrome (PURE) study is a phase II, multicenter, randomized, controlled, unblinded, adaptive design clinical trial that aims to evaluate the safety and efficacy of PUF, using PolyCore™ as the investigational solution, in the treatment of RCHF patients who present with prominent right ventricular failure due to afterload mismatch, functional tricuspid regurgitation and enlarged cava vein consequent to intravascular fluid overload. Approximately 84 patients will be randomized 1:1 either to continue with their prescribed guideline-directed medical therapy or to add the PUF treatment on top of it. The primary objective is to evaluate if PUF treatment has an impact on the composite endpoint of the patient’s mortality or worsening of the patient’s condition such as hospitalization for cardiovascular causes, increasing the initial daily dose of loop diuretic or worsening of renal function. Statistical analysis for the primary endpoint will be standard survival analysis to estimate the failure rate at month 7 for each group via Kaplan-Meier curves. Sensitivity analysis and various secondary analyses, including a multiple events analysis, will be conducted to evaluate the robustness of the primary endpoint results. Safety will be evaluated for up to 12 months. Conclusion: The PURE study was designed to evaluate the safety and efficacy of peritoneal ultrafiltration with PolyCore™ on top of guideline-directed medical therapy in patients with RCHF, assuming a combined clinical endpoint of mortality or worsening patients’ condition. If successful, the treatment should allow for an improvement of the RCHF symptoms, decreasing hospitalization rate of patients.

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.

Comparative assessment of venous congestion severity and hospitalization outcomes in patients with acute decompensated heart failure with preserved ejection fraction

Aim. To characterize the potental of additional paraclinical research methods (ultrasound, determination of body composition) for assessing the congestion severity in patients with acute decompensated heart failure with preserved ejection fraction (ADHFpEF) in the intensive care unit.Material and methods. We examined 82 patients with ADHFpEF aged from 50 to 85 years, who were hospitalized in the intensive care unit of the Veresaev City Clinical Hospital (Moscow). All patients underwent a standard clinical and laboratory examination, including determination of NT-proBNP, as well as echocardiography, chest radiography, bioimpedance analysis, Venous Excess Ultrasound (VExUS), lung ultrasound. Depending on the congestion degree visualized by VExUS, patients were divided into three groups.Results. The median levels of NT-proBNP, E/A and E/e', number of B-lines in one lung segment, ECW and TBW, and the diuretics' dose used in the hospital in pa tients with ADHFpEF and severe congestion were significantly higher. Signs of congestion obtained as a result of X-ray examination did not differ significantly between groups. In-hospital death was associated with higher values of NT-proBNP, E/A ratio, IVC diameter, number of B-lines in one lung segment, ECW and TBW. The odds of death in patients with VExUS Grade 3 increased 20,9 times compared to Grade 1 (95% CI: 1,125-387,688).Conclusion. Higher levels of NT-proBNP, the dose of diuretics used in the hospital, and ECW and TBW were associated with congestion severity. The severity of congestion assessed by VExUS and ECW/TBW are positively associated with inhospital mortality