Diuretic Combination Therapy in Acute Heart Failure: An Updated Review.

Loop diuretics are the cornerstone of decongestive therapy in patients presenting with acute heart failure and have been extensively studied in randomized clinical trials. Therefore, in current guidelines, they are the only drug with a class I recommendation to treat signs and symptoms of congestion when present. However, the percentage of patients achieving successful decongestion is suboptimal, and diuretic resistance frequently develops. Patients with a poor response to loop diuretics and those discharged with residual signs of congestion are characterized by a worse prognosis over time. Recently, a renovated interest in different diuretic classes sprouted among heart failure researchers in order to improve decongestion strategies and ameliorate short- and long-term clinical outcomes. Randomized clinical trials investigating associations among diuretic classes and loop diuretics have been performed but yielded variable results. Therefore, despite initial evidence of a possible benefit from some of these compounds, a definite way to approach diuretic resistance via diuretic combination therapy is still missing. The aim of this review is to summarize current clinical evidence on the use of diuretic combination therapy in patients with acute heart failure and to suggest a possible approach to avoid or counteract diuretic resistance.

Possible sarcopenia and its association with hospital-associated dysphagia and decline in physical function: Findings from a heart failure patients prospective cohort study.

BACKGROUND & AIMS: There is limited evidence regarding the association of sarcopenia with dysphagia and physical function in patients with heart failure. This study examined the association between possible sarcopenia and both swallowing and physical function in individuals with acute heart failure (AHF). METHODS: This prospective cohort study included hospitalized patients with AHF. Possible sarcopenia was assessed on admission using calf circumference and grip strength according to an international diagnostic criteria. The primary outcome was dysphagia at discharge using the Food Intake Level Scale (FILS), and the secondary outcome was physical function at discharge using the Barthel Index (BI). Multiple regression analysis and logistic regression, adjusted for potential confounders, were used to examine the association between possible sarcopenia at admission and FILS and BI at discharge. RESULTS: A total of 320 patients (mean age 81.5 years; 170 women) were included in the analysis; 199 (59.4%) were diagnosed with possible sarcopenia. Multivariate analysis showed that possible sarcopenia at admission was significantly associated with FILS at discharge (ß = -0.1204; p = 0.039). Possible sarcopenia at admission was not significantly associated with BI at discharge (OR = 2.066; 95% CI, 0.910-4.692, p = 0.083). CONCLUSIONS: Possible sarcopenia was associated with decline in swallowing function during hospitalization in patients with AHF. These findings highlight the need for early detection and treatment of possible sarcopenia in this setting.

Increased Spironolactone Dosing in Acute Heart Failure Alters Potassium Homeostasis but Does Not Enhance Decongestion.

BACKGROUND: The ATHENA-HF clinical trial found no improvements in natriuretic peptide levels or clinical congestion when spironolactone 100 mg/day for 96 hours was used in addition to usual treatment for acute heart failure. METHODS: We performed a post hoc analysis of ATHENA-HF to determine whether spironolactone treatment induced any detectable pharmacodynamic effect and whether patients with potentially greater aldosterone activity experienced additional decongestion. Trial subjects previously treated with spironolactone were excluded. We first examined for changes in renal potassium handling. Using the baseline serum potassium level as a surrogate marker of spironolactone activity, we then divided each treatment arm into tertiles of baseline serum potassium and explored for differences in laboratory and clinical congestion outcomes. RESULTS: Among spironolactone-naïve patients, the change in serum potassium did not differ after 24 hours or 48 hours but was significantly larger with spironolactone treatment compared to placebo at 72 hours (0.23±0.55 vs 0.03±0.60 mEq/L, P=0.042) and 96 hours (0.32±0.51 vs 0.13±0.72 mEq/L, P=0.046). While potassium supplementation was similar at treatment start and 24 hours, spironolactone-treated patients required substantially less potassium replacement at 48 hours (24% vs 36%; P=0.048), 72 hours (21% vs 37%; P=0.013), and 96 hours (11% vs 38%; P<0.001). When the treatment arms were divided into tertiles of baseline serum potassium, there were no differences in the 96-hour log N-terminal pro-B-type natriuretic peptide, net fluid loss, urine output, or dyspnea relief between any of the potassium groups, with no effect modification by treatment exposure. CONCLUSIONS: Spironolactone 100 mg/day for 96 hours in patients receiving intravenous loop diuresis for acute heart failure has no clear added decongestive ability but does meaningfully limit potassium wasting.

Inotropic Agents: Are We Still in the Middle of Nowhere?

Inotropes are prescribed to enhance myocardial contractility while vasopressors serve to improve vascular tone. Although these medications remain a life-saving therapy in cardiovascular clinical scenarios with hemodynamic impairment, the paucity of evidence on these drugs makes the choice of the most appropriate vasoactive agent challenging. As such, deep knowledge of their pharmacological and hemodynamic effects becomes crucial to optimizing hemodynamic profile while reducing the potential adverse effects. Given this perspective, it is imperative for cardiologists to possess a comprehensive understanding of the underlying mechanisms governing these agents and to discern optimal strategies for their application across diverse clinical contexts. Thus, we briefly review these agents' pharmacological and hemodynamic properties and their reasonable clinical applications in cardiovascular settings. Critical interpretation of available data and the opportunities for future investigations are also highlighted.

Blood Pressure Variability After Non-invasive Low-level Tragus Stimulation in Acute Heart Failure.

Higher blood pressure (BP) variability (BPV) was shown to be strong predictors of poor cardiovascular outcomes in heart failure (HF). It is currently unknown if low-level tragus stimulation (LLTS) would lead to improvement in BPV in acute HF (AHF). The 22 patients with AHF (median 80 yrs, males 60%) were randomly assigned to active or sham group using an ear clip attached to the tragus (active group) or the earlobe (sham group) for 1 h daily over 5 days. In the active group, standard deviation (SD), coefficient of variation (CV) and δ in SBP were significantly decreased after LLTS (all p < 0.05). All the changes in SD, CV and δ in SBP before and after stimulation were also significantly different between active and sham groups (all p < 0.05). This proof-of-concept study demonstrates the beneficial effects of LLTS on BPV in AHF.

Artificial Intelligence-Based Electrocardiographic Biomarker for Outcome Prediction in Patients With Acute Heart Failure: Prospective Cohort Study.

BACKGROUND: Although several biomarkers exist for patients with heart failure (HF), their use in routine clinical practice is often constrained by high costs and limited availability. OBJECTIVE: We examined the utility of an artificial intelligence (AI) algorithm that analyzes printed electrocardiograms (ECGs) for outcome prediction in patients with acute HF. METHODS: We retrospectively analyzed prospectively collected data of patients with acute HF at two tertiary centers in Korea. Baseline ECGs were analyzed using a deep-learning system called Quantitative ECG (QCG), which was trained to detect several urgent clinical conditions, including shock, cardiac arrest, and reduced left ventricular ejection fraction (LVEF). RESULTS: Among the 1254 patients enrolled, in-hospital cardiac death occurred in 53 (4.2%) patients, and the QCG score for critical events (QCG-Critical) was significantly higher in these patients than in survivors (mean 0.57, SD 0.23 vs mean 0.29, SD 0.20; P<.001). The QCG-Critical score was an independent predictor of in-hospital cardiac death after adjustment for age, sex, comorbidities, HF etiology/type, atrial fibrillation, and QRS widening (adjusted odds ratio [OR] 1.68, 95% CI 1.47-1.92 per 0.1 increase; P<.001), and remained a significant predictor after additional adjustments for echocardiographic LVEF and N-terminal prohormone of brain natriuretic peptide level (adjusted OR 1.59, 95% CI 1.36-1.87 per 0.1 increase; P<.001). During long-term follow-up, patients with higher QCG-Critical scores (>0.5) had higher mortality rates than those with low QCG-Critical scores (<0.25) (adjusted hazard ratio 2.69, 95% CI 2.14-3.38; P<.001). CONCLUSIONS: Predicting outcomes in patients with acute HF using the QCG-Critical score is feasible, indicating that this AI-based ECG score may be a novel biomarker for these patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01389843; https://clinicaltrials.gov/study/NCT01389843.

Distinct Comorbidity Clusters in Patients With Acute Heart Failure: Data From RELAX-AHF-2.

BACKGROUND: Multimorbidity frequently occurs in patients with acute heart failure (AHF). The co-occurrence of comorbidities often follows specific patterns. OBJECTIVES: This study investigated multimorbidity subtypes and their associations with clinical outcomes. METHODS: From the prospective RELAX-AHF-2 (Relaxin for the Treatment of Acute Heart Failure-2) trial, 6,545 patients (26% with HF with preserved ejection fraction, defined as LVEF ≥50%) were classified into multimorbidity groups using latent class analysis. The association between subgroups and clinical outcomes was examined. Validation of these findings was conducted in the RELAX-AHF trial, which comprised 1,161 patients. RESULTS: Five distinct multimorbidity groups emerged: 1) diabetes and chronic kidney disease (CKD) (often male, high prevalence of CKD and diabetes mellitus); 2) ischemic (ischemic HF); 3) elderly/atrial fibrillation (AF) (oldest, high prevalence of AF); 4) metabolic (obese, hypertensive, more often HF with preserved ejection fraction); and 5) young (fewest comorbidities). After adjusting for confounders, patients in the diabetes and CKD (HR: 1.80; 95% CI: 1.50-2.20), elderly/AF (HR: 1.42; 95% CI: 1.20-1.70), and metabolic (HR: 1.40; 95% CI: 1.20-1.80) groups had higher rates of the composite outcome than patients in the young group, primarily driven by differences in rehospitalization. Treatment allocation (placebo or serelaxin) modified these associations (Pinteraction <0.001). Serelaxin-treated patients in the young group were associated with a lower risk for all-cause mortality (HR: 0.59; 95% CI: 0.40-0.90). Similarly, patients from the RELAX-AHF trial clustered in 5 multimorbidity groups. The clinical characteristics and associations with outcomes could also be validated. CONCLUSIONS: Comorbidities naturally clustered into 5 mutually exclusive groups in RELAX-AHF-2, showing variations in clinical outcomes. These data emphasize that the specific combination of comorbidities can influence adverse outcomes and treatment responses in patients with AHF.

Time from admission to randomization and the effect of empagliflozin in acute heart failure: A post-hoc analysis from EMPULSE.

AIMS: Patients hospitalized for acute heart failure (HF) could be enrolled in EMPULSE (NCT04157751) upon haemodynamic stabilization and between 24 h and 5 days after hospital admission. The timing of treatment initiation may influence the efficacy and safety of drugs such as empagliflozin. The aim of this study was to evaluate patient characteristics, clinical events, and treatment effects according to time from admission to randomization. METHODS AND RESULTS: The EMPULSE population was dichotomized by median time from hospital admission to randomization (1-2 days vs. 3-5 days). The primary outcome was a hierarchical composite endpoint of time to all-cause death, number of HF events, time to first HF event, and a ≥5-point difference in Kansas City Cardiomyopathy Questionnaire total symptom score change from baseline after 90 days, analysed using the win ratio (WR) method. Patients randomized later (3-5 days, average time 3.9 days; n = 312) had a higher risk of experiencing clinical events than patients randomized earlier (1-2 days, average time 1.7 days; n = 215). The treatment effect favoured empagliflozin versus placebo in patients randomized later (3-5 days: WR 1.69, 95% confidence interval [CI] 1.26-2.25) but was attenuated in patients randomized earlier (1-2 days: WR 1.04, 95% CI 0.74-1.44) (interaction p = 0.029). A similar pattern was observed for the composite of HF hospitalization or cardiovascular death and all-cause hospitalizations (interaction p < 0.1 for both). The reduction of N-terminal pro-B-type natriuretic peptide levels was more pronounced with empagliflozin among patients randomized later than in patients randomized earlier (interaction p = 0.004). CONCLUSIONS: Among patients hospitalized for acute HF enrolled in EMPULSE, those randomized later after hospital admission (3-5 days) experienced greater clinical benefit with empagliflozin than those randomized earlier (1-2 days). These findings should be confirmed in future studies before clinical application.

Relationship between the HeartMate Risk Score category on admission and outcome in patients with acute heart failure referred to a cardiac intensive care unit.

The HeartMate Risk Score (HMRS), a simple clinical prediction rule based on the patients' age, albumin, creatinine, and the international normalized ratio of the prothrombin time (PT-INR), is correlated with mortality in the cohort of left ventricular assist device (LVAD) recipients. However, in an aging society, an LAVD is indicated for only a small proportion of patients with acute heart failure (AHF), and whether the HMRS has prognostic implications for unselected patients with AHF is unknown. This study aimed to assess the prognostic value of HMRS categories on admission in patients with AHF. We analyzed 339 hospitalized patients with AHF who had albumin, creatinine, and the PT-INR recorded on admission. The patients were categorized as follows: the High group (HMRS > 2.48, n = 131), Mid group (HMRS of 1.58-2.48, n = 97) group, and Low group (HMRS < 1.58, n = 111). The endpoints of this study were all-cause death and readmission for heart failure (HF). During a median follow-up of 247 days, 24 (18.3%) patients died in the High group, 7 (7.2%) died in the Mid group, and 8 (7.2%) died in the Low group. In a multivariable analysis adjusted for highly imbalanced baseline variables, a high HMRS was independently associated with survival, with a hazard ratio of 2.90 (95% confidence interval 1.42-5.96, P = 0.004). With regard to the composite endpoint of all-cause death and readmission for HF, the Mid group had a worse prognosis than the Low group, and the High group had the worst prognosis. A high HMRS on admission is associated with all-cause mortality and readmission for HF, and a mid-HMRS is associated with readmission for HF after AHF hospitalization. The HMRS may be a valid clinical tool to stratify the risk of adverse outcomes after hospitalization in unselected patients with AHF.

Acetazolamide therapy in patients with acute heart failure: a systematic review and meta-analysis of randomized controlled trials.

Acute heart failure (AHF) often leads to unfavorable outcomes due to fluid overload. While diuretics are the cornerstone treatment, acetazolamide may enhance diuretic efficiency by reducing sodium reabsorption. We performed a systematic review and meta-analysis on the effects of acetazolamide as an add-on therapy in patients with AHF compared to diuretic therapy. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCT). A random-effects model was employed to compute mean differences and risk ratios. Statistical analysis was performed using R software. The GRADE approach was used to rate the certainty of the evidence. We included 4 RCTs with 634 patients aged 68 to 81 years. Over a mean follow-up of 3 days to 34 months, acetazolamide significantly increased diuresis (MD 899.2 mL; 95% CI 249.5 to 1549; p < 0.01) and natriuresis (MD 72.44 mmol/L; 95% CI 39.4 to 105.4; p < 0.01) after 48 h of its administration. No association was found between acetazolamide use and WRF (RR 2.4; 95% CI 0.4 to 14.2; p = 0.3) or all-cause mortality (RR 1.2; 95% CI 0.8 to 1.9; p = 0.3). Clinical decongestion was significantly higher in the intervention group (RR 1.35; 95% CI 1.09 to 1.68; p = 0.01). Acetazolamide is an effective add-on therapy in patients with AHF, increasing diuresis, natriuresis, and clinical decongestion, but it was not associated with differences in mortality.

Statin therapy impact on Long-Term outcomes in acute heart Failure: Retrospective analysis of hospitalized patients.

Background: Statin therapy is well-established for treating hyperlipidemia and ischemic heart disease (IHD), but its role in Acute Decompensated Heart Failure (ADHF) remains less clear. Despite varying clinical guidelines, the actual utilization and impact of statin therapy initiation in patients with ADHF with an independent indication for statin therapy have not been thoroughly explored. Methods: We conducted a retrospective observational study on 5978 patients admitted with ADHF between January 1st, 2007, and December 31st, 2017. Patients were grouped based on their statin therapy status at admission and discharge. We performed multivariable analyses to identify independent predictors of short-term, intermediate-term, and long-term mortality. A sensitivity analysis was also conducted on patients with an independent indication for statin therapy but who were not on statins at admission. Results: Of the total patient cohort, 73.9% had an indication for statin therapy. However, only 38.2% were treated with statins at admission, and 56.1% were discharged with a statin prescription. Patients discharged with statins were younger, predominantly male, and had a higher prevalence of IHD and other comorbidities. Statin therapy at discharge was an independent negative predictor of 5-year all-cause mortality (hazard ratio 0.80, 95% confidence interval 0.76-0.85). The sensitivity analysis confirmed these findings, demonstrating higher mortality rates in patients not initiated on statins during admission. Conclusions: The study highlights significant underutilization of statin therapy among patients admitted with ADHF, even when there's an independent indication for such treatment. Importantly, initiation of statin therapy during hospital admission was independently associated with improved long-term survival.

Opioid Intoxication to Withdrawal: A Case of Takotsubo Cardiomyopathy.

Takotsubo cardiomyopathy (TTC) is characterized by a transient reduction in left ventricular systolic function with apical akinesis. TTC is usually associated with stress and emotional responses; however, opioid withdrawal has been identified as a rare cause of precipitation of TTC. We describe the case of an elderly female with chronic opioid dependence, who presented with symptoms of toxicity and developed TTC upon opioid withdrawal. Her symptoms improved with clonidine. In the time of an ongoing opioid crisis and an attempt to reduce opioid use among patients, this case reinforces the importance of anticipating TTC as a possibly life-threatening complication of sudden discontinuation of opioids in patients who have developed dependence on it.

Spot urine sodium-to-creatinine ratio surpasses sodium in identifying poor diuretic response in acute heart failure.

AIMS: We aim to identify the most accurate marker for early prediction of poor diuretic response in acute heart failure (AHF) patients with signs of congestion requiring intravenous diuretic treatment. METHODS: In this single-centre, prospective observational study, AHF patients with signs of congestion received a standardized intravenous furosemide dose (1 mg/kg of body weight; 40 mg in bolus and remaining dose in 2 h continuous infusion). Subsequently, we assessed spot urine composition at 2 h post-administration, comparing it with total urine output at 6 h. Various potential urine markers were analysed for predicting urine output using receiver operating characteristic (ROC) curves and logistic regression models. We investigated guideline-recommended markers, including spot urine sodium (UNa+) and its cut-off, and introduced the UNa+/UCr (urine creatinine concentration) ratio adjusting UNa+ for urine dilution. RESULTS: Out of 111 patients (85% males, 66.4 ± 13.9 years old, NTproBNP 7290 [4493-14 582] pg/ml), there were 18 (16%) with a poor diuretic response (cumulative urine output <600 ml during the first 6 h). The mean 6 h cumulative diuresis in patients with poor and good diuretic response was 406 ± 142 and 2114 ± 1164 ml, respectively, P < 0.005. After an initial evaluation of several potential biomarkers, only UNa+, UCr and UNa+/UCr were selected as candidates with the highest predictive value. The cut-off for UNa+ adjusted for urine dilution: UNa+/UCr ratio <0.167 mmol/mg × 10-1 was determined by ROC analysis with the highest area under the curve (95% confidence interval): 0.956 (0.915-0.997), P < 0.001. When compared with the guideline-recommended cut-off (UNa+ <50 mmol/L as a reference, specificity-0.97; sensitivity-0.83), the odds ratio (OR) for UNa+/UCreat to identify a poor diuretic response was 2.5 times greater, regardless of kidney function (OR for estimated glomerular filtration rate in the logistic regression model was 0.978 [0.945-1.013, P = 0.222]). CONCLUSIONS: The UNa+/UCr ratio in a spot urine sample 2 h after intravenous diuretic administration is a simple, highly predictive marker for the identification of AHF patients with poor diuretic response, surpassing guidelines-recommended markers like UNa+.

Incremental value of C-reactive protein to the MEESSI acute heart failure risk score.

AIMS: We hypothesized that the current gold standard for risk stratification of patients with acute heart failure (AHF), the Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF (MEESSI-AHF) risk score, can be further improved by adding systemic inflammation as quantified by C-reactive protein (CRP). METHODS AND RESULTS: In a prospective multicentre diagnostic study (BASEL V), AHF was centrally adjudicated by two independent cardiologists. The MEESSI-AHF risk score was calculated using an established reduced and recalibrated model containing 12 independent risk factors. Model extension was performed by refitting and adding CRP in the logistic regression model with 30-day mortality as binary outcome. Discrimination, calibration and clinical usefulness were used to assess the performance of the extended Multiple Estimation of risk based on the Emergency department Spanish Score In patients (MEESSI) model. Validation was performed in an independent, retrospective and single-centre AHF cohort. Among 1208 AHF patients with complete data allowing calculation of the recalibrated MEESSI and the extended MEESSI models, the prognostic accuracy for 30-day mortality of the extended MEESSI model (c-statistic 0.83, 95% confidence interval [CI] 0.79-0.87) was significantly higher compared to the recalibrated model (c-statistic 0.79, 95% CI 0.75-0.83, p = 0.013). The extended model allowed to stratify a higher percentage of patients into the lowest risk group compared to the recalibrated model (33.1% vs. 20.3%). Demonstrating a calibration plot's slope of 1.00 (95% CI 0.81-1.19) and an intercept of 0.0 (95% CI -0.22 to 0.22), the extended MEESSI model achieved excellent and improved calibration. Results were confirmed in the independent validation cohort (n = 575). CONCLUSIONS: Quantifying inflammation using CRP concentration provided incremental value in AHF risk stratification using the established MEESSI model.

Setting the optimal threshold of NT-proBNP and BNP for the diagnosis of heart failure in patients over 75 years.

AIMS: Diagnosing acute heart failure (AHF) remains particularly challenging in older patients. Natriuretic peptides are recommended as valuable diagnostic tools in this context. This study aims to establish the diagnostic thresholds of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for AHF in patients aged over 75 years, both with and without co-morbidities. METHODS AND RESULTS: In this retrospective longitudinal multicentre cohort study, data were gathered from 12 071 hospitalized patients aged 75 years or older, presenting with acute dyspnoea and undergoing BNP or NT-proBNP measurement within 48 h of admission across 10 Assistance Publique-Hôpitaux de Paris facilities between 2011 and 2022, encompassing geriatrics, cardiology, and pulmonology departments. Final diagnoses were categorized using ICD-10 criteria as either AHF or other acute respiratory conditions such as COPD exacerbation, pulmonary embolism, and pneumonia. The mean (SD) age of the population was 84.0 (80.0, 89.0) years, with 52.7% being female. Out of these, 7946 (65.8%) were diagnosed with AHF upon discharge. For NT-proBNP, the identified 'optimal' threshold for diagnosing AHF was 1748 ng/L, with a positive predictive value (PPV) of 84%. Among patients aged over 85 years, a threshold of 2235 pg/mL for NT-proBNP was associated with an 84% PPV. In patients with atrial fibrillation (AF), a threshold of 2332 pg/mL for NT-proBNP demonstrated a PPV of 90% for AHF diagnosis. Additionally, in patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min, a threshold of 3474 pg/mL for NT-proBNP yielded a 90% PPV for AHF diagnosis. In male patients, a threshold of 1800 pg/mL showed an 85% PPV for AHF diagnosis, while in patients with obesity, a threshold of 1375 pg/mL demonstrated an 85% PPV for AHF diagnosis. CONCLUSIONS: In older patients, we found significant effects of co-morbidities on natriuretic peptides results, particularly in patients over 85 years old, older patients with abnormal renal function, obesity, and atrial fibrillation. Despite the consideration of those co-morbid conditions, NT-proBNP and BNP level continue to demonstrate utility in the diagnosis of AHF in older patients.

Corrigendum: Analysis of hematological indicators via explainable artificial intelligence in the diagnosis of acute heart failure: a retrospective study.

[This corrects the article DOI: 10.3389/fmed.2024.1285067.].

Intra-aortic balloon pump treatment in an adult patient with a Fontan circulation and acute heart failure: a case report.

Background: There is limited evidence for the use of an intra-aortic balloon pump (IABP) in adult patients with a total cavopulmonary, or Fontan circulation. Case summary: A patient in his twenties with a Fontan circulation presented with sepsis, pneumonia, and pulmonary oedema. He was born with a hypoplastic left ventricle, atrioventricular septal defect, and hypoplastic aortic arch, and a total cavopulmonary circulation had been established within his first years of life. Standard of care treatment with antibiotics, non-invasive ventilatory support, loop diuretics, and vasopressors was initiated. Due to persistent pulmonary congestion and increasing general fatigue, an IABP was placed via a femoral artery to offload the failing systemic ventricle. Secondary to IABP treatment, mean arterial pressure rose, and vasodilatory nitroprusside could be introduced. Over 4 days of IABP treatment, the patient's general condition and ventricular systolic function improved significantly. Discussion: This case suggests that IABP treatment was important in the recovery of our patient with a Fontan circulation, pneumonia, and heart failure. We propose that during IABP treatment, an increase in stroke volume and a reduction in ventricular filling pressure is achieved, thereby increasing the transpulmonary pressure gradient that is central to pulmonary blood flow in Fontan patients. More definitive evidence is necessary to confirm our hypotheses.

Renal function in PUSH-AHF: a summary of newly released data from the 2024 Annual Congress of the Heart Failure Association of the ESC.

The Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure (PUSH-AHF) study, published in August of 2023, was the first randomized clinical trial to compare natriuresis-guided decongestion (based on spot urinary sodium measurement) to standard of care in patients with acute heart failure with congestion receiving loop diuretic therapy. Based on results from their trial, the authors concluded that natriuresis-guided loop diuretic treatment was safe and improved natriuresis and diuresis without impacting long-term clinical outcomes. The original PUSH-AHF trial included limited information about renal outcomes and left clinicians with important questions about how natriuresis-guided decongestion might affect their patients' renal function. On May 12, 2024, however, at the 2024 Annual Congress of the HFA-ESC, Dr. Kevin Damman provided an in-depth exploration of renal outcomes from the trial when he presented a pre-specified, secondary analysis, renal function in the PUSH-AHF trial. This review puts the sub-study findings into context by considering the history of the original trial from which they came from and explaining the need for a close study of its renal outcomes particularly. It highlights the potential impact of renal function in PUSH-AHF on clinical practice and future directions that should be considered by the cardiology research community.

Combining Loop and Thiazide Diuretics Across the Left Ventricular Ejection Fraction Spectrum: The CLOROTIC Trial.

BACKGROUND: The addition of hydrochlorothiazide (HCTZ) to furosemide in the CLOROTIC (Combining Loop with Thiazide Diuretics for Decompensated Heart Failure) trial improved the diuretic response in patients with acute heart failure (AHF). OBJECTIVES: This work aimed to evaluate if these results differ across the spectrum of left ventricular ejection fraction (LVEF). METHODS: This post hoc analysis of the randomized, double-blind, placebo-controlled CLOROTIC trial enrolled 230 patients with AHF to receive either HCTZ or a placebo in addition to an intravenous furosemide regimen. The influence of LVEF on primary and secondary outcomes was evaluated. RESULTS: The median LVEF was 55%: 166 (72%) patients had LVEF >40%, and 64 (28%) had LVEF ≤40%. Patients with a lower LVEF were younger, more likely to be male, had a higher prevalence of ischemic heart disease, and had higher natriuretic peptide levels. The addition of HCTZ to furosemide was associated with the greatest weight loss at 72 of 96 hours, better metrics of diuretic response, and greater 24-hour diuresis compared with placebo, with no significant differences according to the LVEF category (using 2 LVEF cutoff points: 40% and 50%) or LVEF as a continuous variable (all P values were insignificant). There were no significant differences observed with the addition of HCTZ in terms of mortality, rehospitalizations, or safety endpoints (impaired renal function, hyponatremia, and hypokalemia) among the 2 LVEF groups (all P values were insignificant). CONCLUSIONS: Adding HCTZ to intravenous furosemide seems to be effective strategy for improving diuretic response in AHF without treatment effect modification according to baseline LVEF. (Combining Loop with Thiazide Diuretics for Decompensated Heart Failure [CLOROTIC], NCT01647932; Randomized, double blinded, multicenter study, to asses Safety and Efficacy of the Combination of Loop With Thiazide-type Diuretics vs Loop diuretics with placebo in Patients With Decompensated, EudraCT Number 2013-001852-36).