UNASSIGNED: Inflammation is essential in cardiorenal syndrome, however there is still a lack of evidence proving the interaction between cardiac injury, renal dysfunction and the inflammatory response. This study aimed to illustrate the association between renal dysfunction and cardiac injury with a specific focus on the role of inflammation.
UNASSIGNED: A single-center, retrospective study included patients with heart failure admitted to the cardiovascular department from September 2019 to April 2022. Patients received cardiovascular magnetic resonance (CMR) imaging (T1 mapping and late gadolinium enhancement (LGE)). Demographic, creatinine and native T1 were analyzed using pearson correlation, linear regression and adjusted for confounders. Interaction and subgroup analysis were performed.
UNASSIGNED: Finally, 50 validated heart failure (HF) patients (age 58.5 ± 14.8 years; 78.0% men) were included. Cardiac global native T1 for the high estimated glomeruar filtration rate (eGFR) group was 1117.0 ± 56.6 ms, and for the low eGFR group was 1096.5 ± 61.8 ms. Univariate analysis identified global native T1 ( β = 0.16, 95% confidence interval (CI): 0.04-0.28, p = 0.014) and C-reactive protein (CRP) ( β = 0.30, 95% CI: 0.15-0.45, p < 0.001) as determinants of creatinine. Multivariable linear regression analysis identified global native T1 ( β = 0.12, 95% CI: 0.01-0.123, p = 0.040) as a determinant of creatinine while age and diabetes were adjusted. Significant interactions between CRP and global native T1 in relation to creatinine level (p for interaction = 0.005) were identified.
UNASSIGNED: Kidney dysfunction was associated with cardiac injury and inflammation, respectively. The interaction between myocardial injury and kidney dysfunction is contingent on the severity of the inflammatory response. Further studies were needed to identify the mechanisms of the inflammatory response in cardiorenal syndrome.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are recommended in kidney disease and heart failure to reduce adverse clinical outcomes, but utilization can vary. To understand potential gaps in clinical practice and identify opportunities for improvement, we aimed to describe the prevalence and factors associated with SGLT2i prescription in patients with reduced kidney function hospitalized for fluid overload and/or heart failure.
METHODS: Single-center observational study of patients with reduced kidney function (eGFR 20-59 mL/min/1.73 m2) hospitalized for fluid overload or heart failure between January 2022 and December 2023. Data were retrieved from electronic medical records. The outcome was SGLT2i prescription at discharge. Potential variables affecting SGLT2i prescription were identified during stakeholder engagement and evaluated using multivariable logistic regression.
RESULTS: Among 2,543 patients, the median age was 79 (71, 86) years and admission eGFR was 38.7 (28.4, 49.4) mL/min/1.73 m2. SGLT2i was prescribed to 630 (24.8%) patients at discharge. SGLT2i prescription at discharge was independently associated with cardiovascular disease (OR 1.76, 95% CI: 1.31-2.35), diabetes (OR 1.59, 95% CI: 1.19-2.14), fluid overload or heart failure as the primary discharge diagnosis (OR 1.71, 95% CI: 1.29-2.28), SGLT2i pre-hospitalization (OR 104.91, 95% CI: 63.22-174.08), RAS blocker (OR 2.1, 95% CI: 1.65-2.89), and higher eGFR (OR 1.01, 95% CI: 1.003-1.02) at discharge; but inversely associated with older age (OR 0.97, 95% CI: 0.96-0.98).
CONCLUSIONS: SGLT2i prescription at discharge was suboptimal among patients with reduced kidney function hospitalized for fluid overload and/or heart failure, especially in older age and more severe kidney disease. Additionally, cardiovascular disease, diabetes, primary discharge diagnosis of fluid overload or heart failure, prior SGLT2i use, and concurrent RAS blocker at discharge were independently associated with SGLT2i prescription at discharge. Interventions are needed to increase clinicians\' knowledge and overcome clinical inertia to increase SGLT2i use in patients with fluid overload and heart failure.

BACKGROUND: Chronic heart failure (HF) has high rates of mortality and hospitalization in patients with advanced chronic kidney disease (aCKD). However, randomized clinical trials have systematically excluded aCKD population. We have investigated current HF therapy in patients receiving clinical care in specialized aCKD units.
METHODS: The Heart And Kidney Audit (HAKA) was a cross-sectional and retrospective real-world study including outpatients with aCKD and HF from 29 Spanish centers. The objective was to evaluate how the treatment of HF in patients with aCKD complied with the recommendations of the European Society of Cardiology Guidelines for the diagnosis and treatment of HF, especially regarding the foundational drugs: renin-angiotensin system inhibitors (RASi), angiotensin receptor blocker/neprilysin inhibitors (ARNI), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i).
RESULTS: Among 5,012 aCKD patients, 532 (13%) had a diagnosis of HF. Of them, 20% had reduced ejection fraction (HFrEF), 13% mildly reduced EF (HFmrEF), and 67% preserved EF (HFpEF). Only 9.3% of patients with HFrEF were receiving quadruple therapy with RASi/ARNI, BB, MRA, and SGLT2i, but the majority were not on the maximum recommended doses. None of the patients with HFrEF and CKD G5 received quadruple therapy. Among HFmrEF patients, approximately half and two-thirds were receiving RASi and/or BB, respectively, while less than 15% received ARNI, MRA, or SGLT2i. Less than 10% of patients with HFpEF were receiving SGLT2i.
CONCLUSIONS: Under real-world conditions, HF in aCKD patients is sub-optimally treated. Increased awareness of current guidelines and pragmatic trials specifically enrolling these patients represent unmet medical needs.

BACKGROUND: Intra-abdominal pressure (IAP) is a frequently overlooked aspect in clinical assessment that can have a significant impact on organ dysfunction in patients with acute decompensated heart failure (ADHF).
OBJECTIVE: We aimed to investigate dynamics of IAP in patients with ADHF and its impact on diuretic response.
METHODS: We conducted a prospective observational pilot study on a group consisting of 30 patients admitted for ADHF. In every individual IAP measurement, blood and urine samples were taken upon admission, on the second and third days of hospitalization.
RESULTS: The study showed a high (63.3%) prevalence of intra-abdominal hypertension (IAH) defined as IAP ≥12 mm Hg upon admission, while only roughly 13% had signs of ascites. We observed poorer diuresis on the first day of hospitalization in the IAH group (P = 0.03). IAP was negatively correlated with urine output (P = 0.01) and positively correlated with urine osmolality (P = 0.03) on the first day of hospitalization. During follow-up, there was a significant decrease in IAP in patients with IAH upon admission who received standard decongestive therapy.
CONCLUSIONS: The study shows a high prevalence of IAH in patients admitted for ADHF, even in individuals who do not present symptoms of abdominal congestion. Established correlation between IAP, reduced diuresis, and increased urine osmolality, despite achieving target natriuresis, contributes novel insights into the understanding of pathomechanisms underlying diuretic resistance in ADHF.

In cardiorenal syndrome type 1 (CRS1), vascular congestion is central to the pathophysiology of heart failure and thus a key target for management. The venous evaluation by ultrasound (VExUS) system could guide decongestion effectively and thereby improve outcomes.
In this randomized clinical trial, patients with CRS1 (i.e., increase in creatinine ≥0.3 mg/dL) were randomized to guide decongestion with VExUS compared to usual clinical evaluation. The primary endpoint was to assess kidney function recovery (KFR), and the key secondary endpoint was decongestion evaluated by physical examination and changes in brain natriuretic peptide (BNP) and CA-125. Exploratory endpoints included days of hospitalization and mortality.
From March 2022 to February 2023, a total of 140 patients were randomized 1:1 (70 in the VExUS and 70 in the control group). KFR was not statistically different between groups. However, VExUS improved more than twice the odds to achieve decongestion (odds ratio [OR]: 2.6, 95% CI: 1.9-3.0, p = 0.01) and the odds to reach a decrease of BNP >30% (OR: 2.4, 95% CI: 1.3-4.1, p = 0.01). The survival at 90 days, recongestion, and CA-125 were similar between groups.
In patients with CRS1, we observed that VExUS-guided decongestion did not improve the probability of KFR but improved the odds to achieve decongestion.

UNASSIGNED: Little is known about the burden of cardiorenal syndrome (CRS) and cardiorenal anemia syndrome (CRAS) in the Middle East Region. Furthermore, whether the occurrence rates of CRAS differ across heart failure (HF) phenotypes is not widely investigated. We aimed to examine the prevalence of CRS and CRAS in patients with HF, compare characteristics of patients with CRAS-HFrEF vs. CRAS-HFpEF, and investigate anemia association with 1-year all-cause hospitalizations.
UNASSIGNED: HF patients who visited a multidisciplinary HF clinic at a single center between 10-2015 and 06-2022 (n = 968) were retrospectively included. Differences in rates of CRAS prevalence, and patients\' characteristics of those with CRAS-HFrEF vs. CRAS-HFpEF were determined using appropriate testing methods. Generalized estimating equation (GEE) models were used to determine if anemia was associated with higher rates of hospitalization.
UNASSIGNED: CRS was prevalent in 34.4% of subjects, while 25.3% had CRAS. CRAS prevalence rates among patients with HFpEF vs. HFrEF were comparable (27.2% vs. 24.2%, p = 0.3). Compared to patients with HFrEF-CRAS, those with HFpEF-CRAS were more likely females (p < 0.001), had a higher burden of hypertension (p = 0.01), and lower hemoglobin (p = 0.02). In an adjusted GEE model, anemia was associated with an average increase of 1.8 admissions in CRS patients (p = 0.015).
UNASSIGNED: In patients with HF, 1 in 3 patients presented with CRS, and 1 in 4 patients had CRAS. The prevalence of CRAS was comparable among those HFpEF and HFrEF. Anemia was associated with an increased rate of 1-year all-cause hospitalization in CRS patients.

As it is unclear whether there is genetic susceptibility to cardiorenal syndrome (CRS), we conducted a genome-wide association study of dilated cardiomyopathy (DCM)-induced heart failure (HF) associated with renal insufficiency (RI) in a Chinese population to identify putative susceptibility variants and culprit genes.
A total of 99 Han Chinese patients with DCM-induced chronic HF were selected and divided into one of three groups, namely, HF with normal renal function (Group 1), HF with mild RI (Group 2) and HF with moderate to severe RI (Group 3). Genomic DNA was extracted from each subject for genotyping.
According to Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, top 10 lists of molecular function, cell composition and biological process of differential target genes and 15 signalling pathways were discriminated among the three groups. Additionally, sequencing results identified 26 significantly different single-nucleotide polymorphisms (SNPs) in the 15 signalling pathways, including three SNPs (rs57938337, rs6683225 and rs6692782) in ryanodine receptor 2 (RYR2) and two SNPs (rs12439006 and rs16958069) in RYR3. The genotype and allele frequencies of the five SNPs in RYR2 and RYR3 were significantly differential between HF (Group 1) and CRS (Group 2 + 3) patients.
Twenty-six significantly different SNP loci in 17 genes of the 15 KEGG pathways were found in the three patient groups. Among these variants, rs57938337, rs6683225 and rs6692782 in RYR2 and rs12439006 and rs16958069 in RYR3 are associated with RI in Han Chinese patients with heart failure, suggesting that these variants may be used to identify patients susceptible to CRS in the future.

Type 2 diabetes mellitus (T2DM) is a risk factor for cardiac and renal complications; its effect on cardiorenal syndromes is unknown.
In a French nationwide cohort of 5,123,193 patients hospitalized in 2012 with ≥5 years of follow-up, we assessed the effect of T2DM on cardiorenal syndrome (CRS) (using cardiorenal, renocardiac, and simultaneous subtypes) incidence and outcomes using 1:1 propensity matching.
Among 4,605,236 adults without cardiorenal syndrome, 380,581 (8.5%) with T2DM were matched to 380,581 adults without T2DM. During follow-up, CRS occurred in 104,788 patients: simultaneous n = 25,225 (24.0%); cardiorenal n = 51,745 (49.4%); renocardiac n = 27,818 (26.5%). T2DM doubled the risk of incident CRS (1.30% versus 0.65%/year; adjusted hazard ratio (HR) for any cardiorenal syndrome: 2.14 [95% confidence interval 2.10;2.19]; renocardiac: 2.43 [2.34;2.53]; cardiorenal: 2.09 [2.03;2.15]; simultaneous: 1.94 [1.86;2.03]. Among the 26,396 adults with CRS in 2012, 11,355 (43.0%) had T2DM and were younger than non-diabetic adults (77.4 ± 9.5 versus 82.3 ± 10.0); 8,314 patients with T2DM were matched to 8,314 patients without. T2DM increased risk of: end-stage kidney disease, adjusted HR 1.50 [1.39;1.62]; myocardial infarction 1.35 [1.19;1.53]; cardiovascular death 1.20 [1.13;1.27]; heart failure 1.17 [1.12;1.21]; and all-cause death 1.09 [1.06;1.13], but not ischemic stroke.
Patients with T2DM represent almost half of patients with CRS and are younger than their non-diabetic counterparts. T2DM doubles the risk of CRS and increases the risk of death, cardiovascular outcome, and end-stage kidney disease but not ischemic stroke after CRS.

The management of the coexistence of heart disease and kidney disease is increasingly challenging for clinicians. Chronic kidney disease (CKD) is not only a prevalent comorbidity of patients with heart failure but has also been identified as a noteworthy risk factor for all-cause mortality and poor clinical outcomes. Digoxin is one of the commonest treatments for heart disease. There are few trials investigating the role of digoxin in patients with cardiorenal syndrome (CRS). This study aims to examine the association between digoxin usage and clinical outcomes in patients with CRS in a nationwide cohort.
We conducted a population-based study that included 705 digoxin users with CRS; each patient was age, sex, comorbidities, and medications matched with three non-users who were randomly selected from the CRS population. Cox proportional hazards regression analysis was conducted to estimate the effects of digoxin on the incidence of all-cause mortality, congestive heart failure (CHF) hospitalization, coronary artery disease (CAD) hospitalization, and end-stage renal disease (ESRD).
The all-cause mortality rate was significantly higher in digoxin users than in non-users (adjusted hazard ratio [aHR] = 1.26; 95% confidence interval [CI] = 1.09-1.46, p = 0.002). In a subgroup analysis, there was significantly high mortality in the 0.26-0.75 defined daily dose (DDD) subgroup of digoxin users (aHR = 1.49; 95% CI = 1.23-1.82, p<0.001). Thus, the p for trend was 0.013. With digoxin prescription, the CHF hospitalization was significantly higher [subdistribution HR (sHR) = 1.17; 95% CI = 1.05-1.30, p = 0.004], especially in the >0.75 DDD subgroup (sHR = 1.19; 95% CI = 1.01-1.41, p = 0.046; p for trend = 0.006). The digoxin usage lowered the coronary artery disease (CAD) hospitalization in the > 0.75 DDD subgroup (sHR = 0.79; 95% CI = 0.63-0.99, p = 0.048). In renal function progression, more patients with CRS entered ESRD with digoxin usage (sHR = 1.34; 95% CI = 1.16-1.54, p<0.001). There was a significantly greater incidence of ESRD in the < 0.26 DDD and 0.26-0.75 DDD subgroups of digoxin users (sHR = 1.32; 95% CI = 1.06-1.66, p = 0.015; sHR = 1.44; 95% CI = 1.18-1.75; p for trend<0.001).
Digoxin should be prescribed with caution to patients with CRS.

Cardiorenal syndrome (CRS) denotes the bidirectional interaction of chronic kidney disease and heart failure with an adverse prognosis but with a limited understanding of its pathogenesis. This study correlates biochemical blood markers, histopathological and immunohistochemistry features, and 2-deoxy-2-fluoro-D-glucose positron emission tomography (18F-FDG PET) metabolic data in low-dose doxorubicin-induced heart failure, cardiorenal syndrome, and renocardiac syndrome induced on Wistar male rats. To our knowledge, this is the first study that investigates the underlying mechanisms for CRS progression in rats using 18F-FDG PET. Clinical, metabolic cage monitoring, biochemistry, histopathology, and immunohistochemistry combined with PET/MRI (magnetic resonance imaging) data acquisition at distinct points in the disease progression were employed for this study in order to elucidate the available evidence of organ crosstalk between the heart and kidneys. In our CRS model, we found that chronic treatment with low-dose doxorubicin followed by acute 5/6 nephrectomy incurred the highest mortality among the study groups, while the model for renocardiac syndrome resulted in moderate-to-high mortality. 18F-FDG PET imaging evidenced the doxorubicin cardiotoxicity with vascular alterations, normal kidney development damage, and impaired function. Given the fact that standard clinical markers were insensitive to early renal injury, we believe that the decreasing values of the 18F-FDG PET-derived renal marker across the groups and, compared with their age-matched controls, along with the uniform distribution seen in healthy developing rats, could have a potential diagnostic and prognostic yield in cardiorenal syndrome.