Aims
Although acute heart failure (AHF) with volume overload is treated with loop diuretics, their dosing and type of administration are mainly based upon expert opinion. A recent position paper from ...the Heart Failure Association (HFA) proposed a step‐wise pharmacologic diuretic strategy to increase the diuretic response and to achieve rapid decongestion. However, no study has evaluated this protocol prospectively.
Methods and results
The Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT‐HF) study is an international, multicentre, non‐randomized, open‐label, pragmatic study in AHF patients on chronic loop diuretic therapy, admitted to the hospital for intravenous loop diuretic therapy, aiming to enrol 500 patients. Inclusion criteria are as follows: at least one sign of volume overload (oedema, ascites, or pleural effusion), use ≥ 40 mg of furosemide or equivalent for >1 month, and a BNP > 250 ng/L or an N‐terminal pro‐B‐type natriuretic peptide > 1000 pg/L. The study is designed in two sequential phases. During Phase 1, all centres will treat consecutive patients according to the local standard of care. In the Phase 2 of the study, all centres will implement a standardized diuretic protocol in the next cohort of consecutive patients. The protocol is based upon the recently published HFA algorithm on diuretic use and starts with intravenous administration of two times the oral home dose. It includes early assessment of diuretic response with a spot urinary sodium measurement after 2 h and urine output after 6 h. Diuretics will be tailored further based upon these measurements. The study is powered for its primary endpoint of natriuresis after 1 day and will be able to detect a 15% difference with 80% power. Secondary endpoints are natriuresis and diuresis after 2 days, change in congestion score, change in weight, in‐hospital mortality, and length of hospitalization.
Conclusions
The ENACT‐HF study will investigate whether a step‐wise diuretic approach, based upon early assessment of urinary sodium and urine output as proposed by the HFA, is feasible and able to improve decongestion in AHF with volume overload.
There is scarce evidence supporting the clinical utility of congestive intrarenal venous flow (IRVF) patterns in patients with acute heart failure.
This study aims to: 1) investigate the association ...between IRVF patterns and the odds of worsening renal function (WRF); 2) track the longitudinal changes of serum creatinine (sCr) across IRVF at predetermined points and its association with decongestion; and 3) explore the relationship between IRVF/WRF categories and patient outcomes.
IRVF was assessed at baseline (pre–decongestive therapy), 72 hours, and 30 and 90 days postdischarge. Changes in sCr trajectories across dynamic IRVF variations and parameters of decongestion were assessed using linear mixed effect models. The association between IRVF/WRF categories and outcomes was evaluated using univariable/multivariable models.
In this prospective, multicenter study with 188 participants, discontinuous IRVF patterns indicated higher odds of WRF (OR: 3.90 95% CI: 1.24-12.20; P = 0.020 at 72 hours; and OR: 5.76 95% CI: 1.67-19.86; P = 0.006 at 30 days) and an increase in sCr (Δ-72 hours 0.14 mg/dL 95% CI: 0.06-0.22; P = 0.001; Δ-discharge 0.13 mg/dL 95% CI: 0.03-0.23; P = 0.007). However, the diuretic response and decongestion significantly influenced the magnitude of these changes. Patients exhibiting both WRF and discontinuous IRVF at 30 days experienced an increased hazard of adverse events (HR: 5.96 95% CI: 2.63-13.52; P < 0.001).
Discontinuous IRVF identifies patients with higher odds of WRF during admission and postdischarge periods. Nonetheless, adequate diuretic response and decongestion could modify this association. Patients showing both WRF and discontinuous IRVF at 30 days had increased rates of adverse events.
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Purpose of the Work
Although sex-specific differences in heart failure (HF) or kidney disease (KD) have been analyzed separately, the predominant cardiorenal phenotype by sex has not been described. ...This study aims to explore the sex-related differences in cardiorenal syndrome (CRS) in a contemporary cohort of outpatients with HF.
Findings
An analysis of the Cardiorenal Spanish registry (CARDIOREN) was performed. CARDIOREN Registry is a prospective multicenter observational registry including 1107 chronic ambulatory HF patients (37% females) from 13 Spanish HF clinics. Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m
2
was present in 59.1% of the overall HF population, being this prevalence higher in the female population (63.2% vs. 56.6%,
p
= 0.032, median age: 81 years old, IQR:74–86). Among those with kidney dysfunction, women displayed higher odds of showing HF with preserved ejection fraction (HFpEF) (odds ratio OR = 4.07; confidence interval CI 95%: 2.65–6.25,
p
< 0.001), prior valvular heart disease (OR = 1.76; CI 95%:1.13–2.75,
p
= 0.014), anemia (OR: 2.02; CI 95%:1.30–3.14,
p
= 0.002), more advanced kidney disease (OR for CKD stage 3: 1.81; CI 95%:1.04–3.13,
p
= 0.034; OR for CKD stage 4: 2.49, CI 95%:1.31–4.70,
p
= 0.004) and clinical features of congestion (OR:1.51; CI 95%: 1.02–2.25, p = 0.039). On the contrary, males with cardiorenal disease showed higher odds of presenting HF with reduced ejection fraction (HFrEF) (OR:3.13; CI 95%: 1.90–5.16,
p
< 0.005), ischemic cardiomyopathy (OR:2.17; CI 95%: 1.31–3.61,
p
= 0.003), hypertension (OR = 2.11; CI 95%:1.18–3.78,
p
= 0.009), atrial fibrillation (OR:1.71; CI 95%: 1.06–2.75,
p
= 0.025), and hyperkalemia (OR:2.43, CI 95%: 1.31–4.50,
p
= 0.005).
Summary
In this contemporary registry of chronic ambulatory HF patients, we observed sex-related differences in patients with combined heart and kidney disease. The emerging cardiorenal phenotype characterized by advanced CKD, congestion, and HFpEF was predominantly observed in women, whereas HFrEF, ischemic etiology, hypertension, hyperkalemia, and atrial fibrillation were more frequently observed in men.
Patients with combined heart failure (HF) and chronic kidney disease (CKD) have been underrepresented in clinical trials. The prevalence of CKD in these patients and their clinical profile require ...constant evaluation. This study aimed to analyze the prevalence of CKD, its clinical profile, and patterns of use of evidence-based medical therapies in HF across CKD stages in a contemporary cohort of ambulatory patients with HF.
From October 2021 to February 2022, the CARDIOREN registry included 1107 ambulatory HF patients from 13 HF clinics in Spain.
The median age was 75 years, 63% were male, and 48% had heart failure with reduced left ventricular ejection fraction (HFrEF). A total of 654 (59.1%) had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m
, and 122 (11%) patients with eGFR ≥ 60 mL/min/1.73 m
had a urine albumin-creatinin ratio ≥ 30 mg/g. The most important variables associated with lower eGFR were age (R2=61%) and furosemide dose (R2=21%). The proportion of patients receiving an angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin II receptor blockers (ARB), an angiotensin receptor-neprilysin inhibitor (ARNi), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), or a mineralocorticoid receptor antagonist (MRA) progressively decreased with lower eGFR categories. Notably, 32% of the patients with HFrEF and an eGFR <30 mL/min/1.73 m
received the combination of ACEI/ARB/ARNi+beta-blockers+MRA+SGLT2i.
In this contemporary HF registry, 70% of patients had kidney disease. Although this population is less likely to receive evidence-based therapies, structured and specialized follow-up approaches within HF clinics may facilitate the adoption of these life-saving drugs.
La retención renal de sodio y agua, con la consiguiente expansión y redistribución del volumen de líquido extracelular, constituye una de las principales características fisiopatológicas de la ...insuficiencia cardiaca. No obstante, la detección, monitorización y manejo de la congestión continúa representando un verdadero desafío para el clínico. En el presente documento se revisa la literatura histórica y contemporánea acerca de los métodos disponibles para evaluar la congestión desde una perspectiva clínica e integradora, y se discuten aspectos farmacológicos y principios fisiopatológicos fundamentales para el uso óptimo de la terapia con diuréticos.
Renal sodium and water retention with resulting extracellular volume expansion and redistribution are hallmark features of heart failure syndromes. However, congestion assessment, monitoring, and treatment represent a real challenge in daily clinical practice. This document reviewed historical and contemporary evidence of available methods for determining volume status and discuss pharmacological aspects and pathophysiological principles that underlie diuretic use.
Renal sodium and water retention with resulting extracellular volume expansion and redistribution are hallmark features of heart failure syndromes. However, congestion assessment, monitoring, and ...treatment represent a real challenge in daily clinical practice. This document reviewed historical and contemporary evidence of available methods for determining volume status and discuss pharmacological aspects and pathophysiological principles that underlie diuretic use.
La retención renal de sodio y agua con la consiguiente expansión y redistribución del volumen de líquido extracelular constituye una de las principales características fisiopatológicas de la insuficiencia cardiaca. No obstante, la detección, monitorización y manejo de la congestión continúa representando un verdadero desafío para el clínico. En el presente documento se revisa literatura histórica y contemporánea acerca de los métodos disponibles para evaluar la congestión desde una perspectiva clínica e integradora, y se discuten aspectos farmacológicos y principios fisiopatológicos fundamentales para el uso óptimo de la terapia con diuréticos.
Abstract
Introduction and objectives
The Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score was derived and validated as a predictor of mortality after heart transplantation ...(HT). The primary objective of this work is to externally validate the IMPACT score in a contemporary Spanish cohort.
Methods
Spanish Heart Transplant Registry data were used to identify adult (>16 years) HT patients between January 2000 and December 2015. Retransplantation, multiorgan transplantation and patients in whom at least one of the variables required to calculate the IMPACT score was missing were excluded from the analysis (
N
= 2810).
Results
Median value of the IMPACT score was five points (IQR: 3, 8). Overall, 1‐year survival rate was 79.1%. Kaplan‐Meier 1‐year survival rates by IMPACT score categories (0–2, 3–5, 6–9, 10–14, ≥15) were 84.4%, 81.5%, 79.3%, 77.3%, and 58.5%, respectively (Log‐Rank test:
p
< .001). Performance analysis showed a good calibration (Hosmer‐Lemeshow chi‐square for 1 year was 7.56;
p
= .47) and poor discrimination ability (AUC‐ROC .59) of the IMPACT score as a predictive model.
Conclusions
In a contemporary Spanish cohort, the IMPACT score failed to accurately predict the risk of death after HT.
Sacubitril/valsartan (SV) promotes cardiac remodeling and improves prognosis in patients with heart failure (HF). However, the response to the drug may vary between patients and its implementation in ...daily clinical practice has been slower than expected. Our objective was to develop a score predicting the super-response to SV in HF outpatients.
This is a retrospective analysis of 185 consecutive patients prescribed SV from two tertiary hospitals between September 2016 and February 2018. Super-responder was defined as a patient taking the drug and (i) without HF admissions, death, or heart transplant, and (ii) with a ≥50% reduction in NT-proBNP levels and/or an increase of ≥10 points in LVEF in a 12-month follow-up period after starting SV. Clinical, echocardiographic, ECG, and biochemical variables were used in a logistic regression analysis to construct a score for super-response to SV which was internally validated using bootstrap method.
Out of 185 patients, 65 (35%) fulfilled the super-responder criteria. Predictors for super-response to SV were absence of both previous aldosterone antagonist and diuretic treatment, NYHA I-II class, female gender, previous 1-year HF admission, and sinus rhythm. An integrating score distinguished a low- (<25%), intermediate- (∼46%), and high-probability (>80%) for 1-year super-response to SV. The AUC for the model was 0.72 (95%CI: 0.64-0.80), remaining consistent after internal validation.
One-third of our patients presented a super-response to SV. We propose an easy-to-calculate score to predict super-response to SV after 1-year initiation based on variables that are currently assessed in clinical practice.
Aims
Pulmonary hypertension (PH) associated with left heart disease is an increasingly prevalent problem, orphan of targeted therapies, and related to a poor prognosis, particularly when pre‐ and ...post‐capillary PH combine. The current study aimed to determine whether treatment with the selective β3 adrenoreceptor agonist mirabegron improves outcomes in patients with combined pre‐ and post‐capillary PH (CpcPH).
Methods and results
The β3 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure (SPHERE‐HF) trial is a multicentre, randomized, parallel, placebo‐controlled clinical trial that enrolled stable patients with CpcPH associated with symptomatic heart failure. A total of 80 patients were assigned to receive mirabegron (50 mg daily, titrated till 200 mg daily, n = 39) or placebo (n = 41) for 16 weeks. Of them, 66 patients successfully completed the study protocol and were valid for the main analysis. The primary endpoint was the change in pulmonary vascular resistance (PVR) on right heart catheterization. Secondary outcomes included the change in right ventricular (RV) ejection fraction by cardiac magnetic resonance or computed tomography, other haemodynamic variables, functional class, and quality of life. The trial was negative for the primary outcome (placebo‐corrected mean difference of 0.62 Wood units, 95% confidence interval CI −0.38, 1.61, p = 0.218). Patients receiving mirabegron presented a significant improvement in RV ejection fraction as compared to placebo (placebo‐corrected mean difference of 3.0%, 95% CI 0.4, 5.7%, p = 0.026), without significant differences in other pre‐specified secondary outcomes.
Conclusions
SPHERE‐HF is the first clinical trial to assess the potential benefit of β3 adrenergic agonists in PH. The trial was negative since mirabegron did not reduce PVR, the primary endpoint, in patients with CpcPH. On pre‐specified secondary outcomes, a significant improvement in RV ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life.
Summary of the study outline, flowchart, and results of the primary and secondary outcomes. The β3 selective agonist mirabegron did not improve pulmonary haemodynamics in adult patients with combined pre‐ and post‐capillary pulmonary hypertension associated with symptomatic heart failure. On secondary outcomes, a significant improvement in right ventricular ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life. PP, per protocol population.
Mini‐
We report the case of a 71‐year‐old man admitted with acute heart failure and suspicion of infective endocarditis (IE). Three‐dimensional transesophageal echocardiography (3DTEE) showed ...ruptured aneurysm of anterior mitral leaflet (AAML) in scallop A2 with severe mitral regurgitation and perforation of right and noncoronary aortic cusps with severe aortic regurgitation. TEE is more sensitive than transthoracic echocardiography for the diagnosis of AAML and 3DTEE provides further morphological information as well about the relationship with adjacent structures. This information has important implications for medical and surgical purposes.
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